THISISABORZOIBOOKPUBLISHEDBYALFREDA.KNOPF

Copyright©2013byScottStossel

Allrightsreserved.PublishedintheUnitedStatesbyAlfredA.Knopf,adivisionof

RandomHouseLLC,NewYork,andinCanadabyRandomHouseofCanadaLimited,Toronto,PenguinRandomHouseCompanies.

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LibraryofCongressCataloging-in-PublicationDataStossel,Scott.

Myageofanxiety:fear,hope,dread,andthesearchforpeaceofmind/ScottStossel.—Firstedition.

pagescmIncludesbibliographicalreferences.

ISBN978-0-307-26987-4(hardcover)

eBookISBN:978-0-385-35132-41.Anxiety.2.Anxiety—

Chemotherapy.3.Anxietydisorders—Epidemiology.4.Tranquilizing

drugs—Socialaspects.5.Stossel,Scott—Mentalhealth.I.

Title.RC531.S782014

616.85’22—dc232013006336

JacketdesignbyCarolCarson

v3.1

ForMarenandNathaniel—mayyoubespared.

Contents

CoverTitlePageCopyrightDedication

PARTI

TheRiddleofAnxietyONETheNatureof

AnxietyTWOWhatDoWeTalk

AboutWhenWeTalkAboutAnxiety?

PARTII

AHistoryofMyNervousStomachTHREEARumblingin

theBelly

FOURPerformanceAnxiety

PARTIII

DrugsFIVE“ASackof

Enzymes”SIXABriefHistoryof

Panic;or,HowDrugsCreatedaNewDisorder

SEVENMedicationandtheMeaningofAnxiety

PARTIV

NurtureVersusNatureEIGHTSeparation

AnxietyNINEWorriersand

Warriors:TheGeneticsofAnxiety

TENAgesofAnxiety

PARTV

RedemptionandResilience

ELEVENRedemptionTWELVEResilience

AcknowledgmentsNotesBibliographyANoteAbouttheAuthorOtherBooksbyThisAuthor

PARTI

TheRiddleofAnxiety

CHAPTER1

TheNatureofAnxiety

And no GrandInquisitor has inreadiness such terrible

torturesashasanxiety,andnospyknowshowto attackmore artfullythe man he suspects,choosing the instantwhen he is weakest,nor knows how to laytraps where he will becaught and ensnared,as anxiety knowshow,and no sharpwittedjudge knows how tointerrogate, to examine

the accused as anxietydoes, which never letshim escape, neither bydiversion nor by noise,neither at work nor atplay, neither by daynorbynight.—SØRENKIERKEGAARD,TheConceptofAnxiety

(1844)

There is no question

that the problem ofanxietyisanodalpointat which the mostvarious and importantquestions converge, ariddle whose solutionwould be bound tothrow a flood of lighton our whole mentalexistence.—SIGMUNDFREUD,IntroductoryLectures

onPsycho-Analysis(1933)

I have an unfortunatetendency to falter atcrucialmoments.Forinstance,standingat

the altar in a church inVermont, waiting for mywife-to-be to come downthe aisle to marry me, I

start to feel horribly ill.Not just vaguely queasy,butseverelynauseatedandshaky—and, most of all,sweaty. The church is hotthat day—it’s early July—and many people areperspiringintheirsummersuits and sundresses. Butnot like I am. As theprocessional plays, sweatbegins to bead on myforehead and above my

upper lip. In weddingphotos, you can see mestanding tensely at thealtar,agrimhalf smileonmy face, as I watch myfiancée come down theaisle on the arm of herfather: in the photos,Susanna is glowing; I amglistening.Bythetimeshejoinsmeinthefrontofthechurch, rivulets of sweatare running into my eyes

and dripping down mycollar.Weturntofacetheminister. Behind him arethe friendswe have askedtogivereadings,andIseethem looking at me withmanifest concern. What’swrongwith him? I imaginethey are thinking. Is hegoing to pass out? Merelyimagining these thoughtsmakes me sweat evenmore. My best man,

standingafewfeetbehindme, taps me on theshoulder and hands me atissue to mop my brow.My friend Cathy, sittingmany rows back in thechurch, will tell me laterthatshehadastrongurgeto bring me a glass ofwater; it looked, she said,as if I had just run amarathon.The wedding readers’

facial expressions havegonefromregisteringmildconcerntowhatappearstome to be unconcealedhorror: Is he going to die?I’m beginning to wonderthat myself. For I havestarted to shake. I don’tmeanslight trembling, thesort of subtle tremor thatwouldbeevidentonly if Iwere holding a piece ofpaper—I feel like I’m on

the verge of convulsing. Iam concentrating onkeeping my legs fromflying out from under melike an epileptic’s and amhoping that my pants arebaggy enough to keep thetrembling from being toovisible.I’mnowleaningonmy almost wife—there isno hiding the tremblingfromher—andsheisdoingherbesttoholdmeup.

The minister is droningon; I have no idea whathe’s saying. (I am not, asthey say, present in themoment.) I’m praying forhim to hurry up so I canescape this torment. Hepauses and looks down atmy betrothed and me.Seeing me—the sheen offlopsweat,thepanicinmyeyes—he is alarmed. “Areyou okay?” he mouths

silently. Helplessly, I nodthat I am. (Because whatwouldhedoifIsaidthatIwasn’t? Clear the church?The mortification wouldbeunbearable.)As theminister resumeshis sermon,hereare threethings I am activelyfighting:theshakingofmylimbs; the urge to vomit;and unconsciousness. AndthisiswhatIamthinking:

Get me out of here. Why?Because there are nearlythree hundred people—friends and family andcolleagues—watching usget married, and I amabout to collapse. I havelost control of my body.Thisissupposedtobeoneof the happiest, mostsignificantmomentsofmylife, and I ammiserable. IworryIwillnotsurvive.

As I sweat and swoonand shake, struggling tocarry out the weddingritual (saying “I do,”putting the rings on,kissing the bride), I amworryingwretchedlyaboutwhat everyone (my wife’sparents, her friends, mycolleagues) must bethinking as they look atme: Is he having secondthoughts about getting

married? Is this evidence ofhis essential weakness? Hiscowardice? His spousalunsuitability? Any doubtthat any friend of mywife’s had, I fear, is beingconfirmed. I knew it, Iimagine those friendsthinking. This proves he’snotworthyofmarryingher.IlookasthoughI’vetakena shower with my clotheson. My sweat glands—my

physical frailty, my weakmoral fiber—have beenrevealedtotheworld.Theunworthiness of my veryexistence has beenexposed.Mercifully, the

ceremony ends. Drenchedin sweat, Iwalkdown theaisle,clinginggratefullytomy new wife, and whenwegetoutsidethechurch,the acute physical

symptoms recede. I’m notgoingtohaveconvulsions.I’m not going to pass out.But as I stand in thereception line, and thendrink and dance at thereception, I’mpantomiming happiness.I’msmilingforthecamera,shaking hands—andwanting to die. And whynot?Ihavefailedatoneofthemostelementalofmale

jobs:gettingmarried.Howhave I managed to cockthis up, too? For the nextseventy-two hours, Iendure a brutal, self-laceratingdespair.

Anxiety kills relativelyfew people, but manymore would welcomedeathasanalternativeto the paralysis andsuffering resulting from

anxiety in its severeforms.—DAVIDH.BARLOW,AnxietyandItsDisorders(2004)

MyweddingwasnotthefirsttimeI’dbrokendown,norwas it the last.At thebirthofourfirstchild,thenurses had to briefly stopministering to my wife,

who was in the throes oflabor,toattendtomeasIturned pale and keeledover. I’ve frozen,mortifyingly, onstage atpublic lectures andpresentations, and onseveral occasions I havebeen compelled to runoffstage. I’ve abandoneddates, walked out ofexams, and hadbreakdowns during job

interviews, on planeflights, train trips,and carrides, and simply walkingdown the street. Onordinary days, doingordinarythings—readingabook, lyinginbed,talkingon the phone, sitting in ameeting, playing tennis—Ihave thousands of timesbeen stricken by apervasive sense ofexistentialdreadandbeen

beset by nausea, vertigo,shaking, and a panoply ofother physical symptoms.In these instances, I havesometimesbeenconvincedthat death, or somethingsomehow worse, wasimminent.Even when not actively

afflicted by such acuteepisodes, Iambuffetedbyworry: about my healthand my family members’

health; about finances;about work; about therattle in my car and thedripping in my basement;abouttheencroachmentofold age and theinevitability of death;about everything andnothing. Sometimes thisworrygetstransmutedintolow-grade physicaldiscomfort—stomachaches, headaches,

dizziness, pains in myarms and legs—or ageneralmalaise,asthoughI have mononucleosis ortheflu.Atvarioustimes, Ihave developed anxiety-induced difficultiesbreathing, swallowing,even walking; thesedifficulties then becomeobsessions, consuming allofmythinking.I also suffer from a

numberofspecificfearsorphobias. To name a few:enclosed spaces(claustrophobia); heights(acrophobia); fainting(asthenophobia); beingtrapped far from home (aspecies of agoraphobia);germs (bacillophobia);cheese (turophobia);speaking in public (asubcategory of socialphobia); flying

(aerophobia); vomiting(emetophobia); and,naturally, vomiting onairplanes(aeronausiphobia).When Iwas a child andmy mother was attendinglawschoolatnight,Ispentevenings at home with ababysitter, abjectlyterrified that my parentshaddied inacar crashorhad abandoned me (the

clinical term for this is“separation anxiety”); byage seven I had worngrooves in the carpet ofmy bedroom with myrelentlesspacing,tryingtowill my parents to comehome.Duringfirstgrade,Ispent nearly everyafternoon for months inthe school nurse’s office,sick with psychosomaticheadaches, begging to go

home; by third grade,stomachaches hadreplaced headaches, butmy daily trudge to theinfirmary remained thesame. During high school,I would purposely losetennisandsquashmatchesto escape the agony ofanxiety that competitivesituations would provokein me. On the one—theonly one—date I had in

high school, when theyoungladyleanedinforakiss during a romanticmoment(wewereoutside,gazing at constellationsthrough her telescope), Iwas overcome by anxietyand had to pull away forfear that I would vomit.My embarrassment wassuch that I stoppedreturningherphonecalls.Inshort,Ihavesincethe

age of about two been atwitchybundleofphobias,fears, and neuroses. And Ihave,since theageof ten,whenIwasfirsttakentoamental hospital forevaluation and thenreferred to a psychiatristfor treatment, tried invarious ways to overcomemyanxiety.Here’s what I’ve tried:individual psychotherapy

(three decades of it),family therapy, grouptherapy, cognitive-behavioral therapy (CBT),rational emotive therapy(RET), acceptance andcommitment therapy(ACT), hypnosis,meditation, role-playing,interoceptive exposuretherapy, in vivo exposuretherapy, supportive-expressive therapy, eye

movement desensitizationand reprocessing (EMDR),self-help workbooks,massage therapy, prayer,acupuncture, yoga, Stoicphilosophy, andaudiotapes I ordered off alate-nightTVinfomercial.Andmedication. Lots of

medication. Thorazine.Imipramine. Desipramine.Chlorpheniramine. Nardil.BuSpar. Prozac. Zoloft.

Paxil. Wellbutrin. Effexor.Celexa.Lexapro.Cymbalta.Luvox. Trazodone.Levoxyl. Propranolol.Tranxene. Serax. Centrax.St. John’swort. Zolpidem.Valium. Librium. Ativan.Xanax.Klonopin.Also: beer, wine, gin,

bourbon, vodka, andscotch.Here’s what’s worked:

nothing.

Actually, that’s notentirely true. Some drugshave helped a little, forfinite periods of time.Thorazine (anantipsychotic, which usedtobe classifiedasamajorsedative) and imipramine(a tricyclicantidepressant)combinedtohelpkeepmeout of the psychiatrichospital in the early1980s, when I was in

middleschoolandravagedby anxiety. Desipramine,another tricyclic, got methroughmyearlytwenties.Paxil(aselectiveserotoninreuptake inhibitor, orSSRI) gave me about sixmonths of significantlyreducedanxietyinmylatetwenties before the fearbroke through again.AmplequantitiesofXanax,propranolol,andvodkagot

me (barely) through abook tour and variouspublic lectures and TVappearances in my earlythirties. A double scotchplus a Xanax and aDramamine cansometimes, whenadministered beforetakeoff, make flyingtolerable—and twodoublescotches, whenadministered in quick

enough succession, canobscure existential dread,makingitseemfuzzierandfurtheraway.But none of thesetreatments havefundamentallyreducedtheunderlying anxiety thatseemswoven intomysouland hardwired into mybody and that at timesmakesmylifeamisery.Astheyearspass,thehopeof

beingcuredofmyanxietyhas faded into a resigneddesire to come to termswith it, to find someredemptive quality ormitigating benefit to mybeing, too often, aquivering, quaking,neuroticwreck.

Anxiety is the mostprominent mentalcharacteristic of

Occidentalcivilization.—R.R.WILLOUGHBY,MagicandCognatePhenomena(1935)

Anxiety and itsassociated disordersrepresent the mostcommon form of officiallyclassifiedmental illness inthe United States today,more common even than

depressionandothermooddisorders.AccordingtotheNational Institute ofMental Health, some fortymillion Americans, nearlyone in seven of us, aresuffering from some kindof anxiety disorder at anygiven time,accounting for31 percent of theexpenditures on mentalhealth care in the UnitedStates.Accordingtorecent

epidemiological data, the“lifetime incidence” ofanxiety disorder is morethan25percent—which,iftrue, means that one infourofuscanexpecttobestricken by debilitatinganxiety at some point inour lifetimes. And it isdebilitating: Recentacademic papers haveargued that the psychicand physical impairment

tied to living with ananxiety disorder isequivalent to living withdiabetes—usuallymanageable, sometimesfatal,andalwaysapaintodeal with. A studypublished inTheAmericanJournal of Psychiatry in2006 found thatAmericansloseacollective321 million days of workbecause of anxiety and

depression each year,costing the economy $50billion annually; a 2001paper published by theU.S. Bureau of LaborStatistics once estimatedthatthemediannumberofdays missed each year byAmerican workers whosuffer from anxiety orstress disorders is twenty-five. In 2005—three yearsbeforetherecenteconomic

crisishit—Americansfilledfifty-three millionprescriptions for just twoantianxiety drugs: Ativanand Xanax. (In the weeksafter 9/11, Xanaxprescriptions jumped 9percentnationally—andby22 percent in New YorkCity.) In September 2008,theeconomiccrashcausedprescriptions in New YorkCity to spike: as banks

went belly up and thestock market went intofree fall, prescriptions foranti-depressant andantianxiety medicationsincreased 9 percent overthe year before, whileprescriptions for sleepingpillsincreased11percent.Though some have

argued that anxiety is aparticularly Americanaffliction, it’s not just

Americanswhosufferfromit. A report published in2009bytheMentalHealthFoundation in Englandfound that fifteen percentof people living in theUnited Kingdom arecurrentlysufferingfromananxiety disorder and thatrates are increasing: 37percent of British peoplereport feeling morefrightened than they used

to. A recent paper in TheJournal of the AmericanMedical Associationobserved that clinicalanxiety is the mostcommon emotionaldisorder in manycountries. Acomprehensive globalreview of anxiety studiespublished in 2006 in TheCanadian Journal ofPsychiatry concluded that

as many as one in sixpeople worldwide will beafflicted with an anxietydisorderforatleastayearduringsomepoint in theirlifetimes; other studieshave reported similarfindings.Of course, these figuresrefer only to people, likeme,whoare,according tothe somewhat arbitrarydiagnostic criteria

established by theAmerican PsychiatricAssociation, technicallyclassifiable as clinicallyanxious. But anxietyextends far beyond thepopulationoftheofficiallymentally ill. Primary carephysicians report thatanxiety isoneof themostfrequent complaintsdriving patients to theiroffices—more frequent, by

some accounts, than thecommon cold. One large-scale study from 1985found that anxietyprompted more than 11percent of all visits tofamilydoctors;astudythefollowing year reportedthat as many as one inthree patients complainedto their family physiciansof“severeanxiety.”(Otherstudies have reported that

20percentofprimarycarepatients in America aretaking a benzodiazepinesuchasValiumorXanax.)Andalmosteveryonealivehas at some pointexperienced the tormentsofanxiety—oroffearorofstress or of worry, whichare distinct but relatedphenomena. (Those whoare unable to experienceanxiety are, generally

speaking, more deeplypathological—and moredangeroustosociety—thanthose who experience itacutely or irrationally;they’resociopaths.)Fewpeopletodaywoulddispute that chronic stressis ahallmarkof our timesorthatanxietyhasbecomea kind of culturalcondition of modernity.We live, as has been said

manytimessincethedawnof the atomic era, in anage of anxiety—and that,cliché though it may be,seems only to havebecome more true inrecent years as Americahasbeenassaultedinshortorder by terrorism,economic calamity anddisruption,andwidespreadsocialtransformation.And yet, as recently as

thirty years ago, anxietyper se did not exist as aclinical category. In 1950,when the psychoanalystRollo May published TheMeaning of Anxiety, heobservedthatatthatpointonly two others, SørenKierkegaard and SigmundFreud, had undertakenbook-length treatments ofthe idea of anxiety. In1927, according to the

listing in PsychologicalAbstracts, only threeacademic papers onanxietywerepublished; in1941, there were onlyfourteen; and as late as1950, there were onlythirty-seven. The first-everacademic conferencededicated solely to thetopicofanxietydidn’ttakeplace until June 1949.Only in 1980—after new

drugs designed to treatanxiety had beendeveloped and brought tomarket—were the anxietydisorders finallyintroduced into the thirdedition of the AmericanPsychiatric Association’sDiagnostic and StatisticalManualofMentalDisorders,displacing the Freudianneuroses. In an importantsense, the treatment

predated the diagnosis—that is, the discovery ofantianxiety drugs drovethecreationofanxietyasadiagnosticcategory.Today, thousands ofpapers about anxiety arepublished each year;several academic journalsarewhollydedicatedtoit.Anxiety research isconstantly yielding newdiscoveries and insights

not only about the causesof and treatments foranxiety but also, moregenerally, about how themind works—about therelationships betweenmind and body, betweengenes and behavior, andbetween molecules andemotion. Using functionalmagnetic resonanceimaging (fMRI)technology, we can now

map various subjectivelyexperiencedemotionsontospecific parts of the brainand can even distinguishvarious types of anxietybased on their visibleeffect on brain function.For instance, generalizedworry about future events(my concern aboutwhether the publishingindustry will survive longenough for this book to

come out, say, or aboutwhether my kids will beable to afford to go tocollege)tendstoappearashyperactivityinthefrontallobes of the cerebralcortex. The severe anxietythat some peopleexperience while speakingin public (like the sheerterror—dulled by drugsand alcohol—that Iexperiencedwhilegivinga

lecture the other day) orthat some extremely shypeople experience insocializing tends to showup as excessive activity inwhat’s called the anteriorcingulate. Obsessive-compulsive anxiety,meanwhile, can manifestitself on a brain scan as adisturbance in the circuitlinking the frontal lobeswith the lower brain

centers within the basalganglia. We now know,thanks to pioneeringresearch by theneuroscientist JosephLeDoux in the 1980s, thatmost fearful emotions andbehaviors are in one wayoranotherproducedby,oratleastprocessedthrough,the amygdala, a tinyalmond-shaped organ atthe base of the brain that

has become the target ofmuch of theneuroscientificresearchonanxiety over the lastfifteenyears.We also know far morethanFreudorKierkegaarddid about how differentneurotransmitters—suchasserotonin, dopamine,gamma-aminobutyric acid,norepinephrine, andneuropeptideY—reduceor

increase anxiety. And weknow there is a stronggenetic component toanxiety; we are evenstarting to learn in somedetail what thatcomponent consists of. In2002, to cite just oneexample among manyhundreds, researchers atHarvard Universityidentified what the mediacalled the “Woody Allen

gene” because it activatesaspecificgroupofneuronsin the amygdala andelsewhere in the crucialparts of the neural circuitgoverning fearfulbehavior. Today,researchers are homing inon numerous such“candidate genes,”measuring the statisticalassociation betweencertain genetic variations

and certain anxietydisorders and exploringthe chemical andneuroanatomicalmechanisms that“mediate” thisassociation,tryingtodiscoverpreciselywhat it is that converts agenetic predisposition intoanactual anxious emotionordisorder.“The real excitementhere, both in the study of

anxietyasanemotionandin the class of disorders,”saysDr.Thomas Insel, thehead of the NationalInstituteofMentalHealth,“is that it’s one of theplaceswherewecanbeginto make the transitionbetweenunderstandingthemolecules, the cells, andthe system right to theemotionandbehavior.Weare now finally able to

drawthelinesbetweenthegenes, the cells, and thebrainandbrainsystems.”

Fear arises from aweakness of mind andtherefore does notappertain to the use ofreason.—BARUCHSPINOZA(CIRCA1670)

And yet for all theadvances brought by thestudy of neurochemistryand neuroanatomy, myown experience suggeststhatthepsychologicalfieldremains riven by disputesover what causes anxietyand how to treat it. Thepsychopharmacologistsand psychiatrists I’veconsulted tell me thatdrugs are a treatment for

my anxiety; the cognitive-behavioral therapists I’veconsulted sometimes tellmethatdrugsarepartlyacauseofit.The clash betweencognitive-behavioraltherapy andpsychopharmacology ismerely the latest iterationof a debate that is severalmillennia old. Molecularbiology, biochemistry,

regression analysis, andfunctional magneticresonance imaging—all ofthese developments havemade possible discoveriesandscientificrigor,aswellas courses of treatment,that Freud and hisintellectualforebearscouldscarcely have dreamed of.Yet while what ThomasInsel of the NIMH saysabout anxiety research

being at the cutting edgeof scientific inquiry intohumanpsychology is true,it is also true that in animportant sense there isnothing new under thesun.Thecognitive-behavioral

therapists’antecedentscanbe traced to theseventeenth-centuryJewish-Dutch philosopherBaruch Spinoza, who

believed anxiety was amere problem of logic.Faulty thinking causes usto fear things we cannotcontrol, Spinoza argued,presaging by more thanthree hundred years thecognitive-behavioraltherapists’ argumentsaboutfaultycognitions.(Ifwe can’t controlsomething, there’s novalue in fearing it, since

the fear accomplishesnothing.) Spinoza’sphilosophyseemedtohaveworked for him;biographies report him tohavebeenanotablysereneindividual. Some sixteenhundred years beforeSpinoza, the Stoicphilosopher Epictetusanticipated the same ideaabout faulty cognitions.“People are not disturbed

by things but by the viewthey take of them,” hewrote in the first century;for Epictetus, the roots ofanxiety lay not in ourbiology but in how weapprehend reality.Alleviating anxiety is amatter of “correctingerroneousperceptions” (asthe cognitive-behavioraltherapistssay).TheStoics,in fact, may be the true

progenitors of cognitive-behavioral therapy. WhenSeneca,acontemporaryofEpictetus, wrote, “Thereare more things to alarmusthantoharmus,andwesuffer more inapprehension than inreality,” he wasprefiguring by twentycenturies what AaronBeck, the official founderof CBT, would say in the

1950s.*The intellectual

antecedents of modernpsychopharmacology lieeven further in the past.Hippocrates, the ancientGreekdoctor,concludedinthefourthcenturyB.C.thatpathologicalanxietywasastraightforward biologicaland medical problem. “Ifyoucutopen thehead[ofamentallyillindividual],”

Hippocrates wrote, “youwill find the brain humid,full of sweat and smellingbadly.” For Hippocrates,“body juices” were thecause of madness; asuddenfloodofbiletothebrain would produceanxiety. (FollowingHippocrates, Aristotleplacedgreatweightonthetemperature of bile:warmbilegeneratedwarmthand

enthusiasm; cold bileproduced anxiety andcowardice.) InHippocrates’s view,anxiety and otherpsychiatric disorders werea medical-biologicalproblem best treated bygetting the humors backintoproperequilibrium.†But Plato and his

adherents, for their part,believed that psychic life

was autonomous fromphysiology and disagreedwith the idea that anxietyor melancholy had anorganic basis in the body;the biological model ofmental illnesswas, as oneancient Greek philosopherputit,“asvainasachild’sstory.” In Plato’s view,while physicians couldsometimes provide relieffor minor psychological

ailments (becausesometimes emotionalproblemsarerefractedintothe body), deep-seatedemotional problems couldbe addressed only byphilosophers. Anxiety andother mental discomfortarose not fromphysiological imbalancesbut from disharmony ofthe soul; recoverydemanded deeper self-

knowledge, more self-control, and a way of lifeguided by philosophy.Platobelievedthat(asonehistorianofsciencehasputit)“ifone’sbodyandmindare in generally goodshape, a doctor can comealongandputminorillstorightjustasonemightcallin a plumber; but if thegeneral fabric is impaired,a physician is useless.”

Philosophy, in this view,was the only propermethod for treating thesoul.Poppycock, said

Hippocrates: “All thatphilosophers have writtenonnaturalsciencenomorepertains to medicine thantopainting,”hedeclared.‡Ispathologicalanxietya

medical illness, asHippocrates and Aristotle

and modernpharmacologists wouldhave it? Or is it aphilosophical problem, asPlatoandSpinozaand thecognitive-behavioraltherapists would have it?Is it a psychologicalproblem, a product ofchildhood trauma andsexual inhibition,asFreudand his acolytes wouldhaveit?Orisitaspiritual

condition, as SørenKierkegaard and hisexistentialist descendantsclaimed?Or,finally,isit—asW.H.AudenandDavidRiesmanandErichFrommand Albert Camus andscores of moderncommentators havedeclared—a culturalcondition, a function ofthe times we live in andthe structure of our

society?Thetruthisthatanxietyis at once a function ofbiology and philosophy,body and mind, instinctand reason, personalityand culture. Even asanxietyisexperiencedataspiritualandpsychologicallevel, it is scientificallymeasurable at themolecular level and thephysiological level. It is

producedbynature and itisproducedbynurture.It’sa psychologicalphenomenon and asociological phenomenon.In computer terms, it’sboth a hardware problem(I’m wired badly) and asoftware problem (I runfaulty logic programs thatmake me think anxiousthoughts).Theoriginsofatemperament are many

faceted; emotionaldispositionsthatmayseemto have a simple, singlesource—a bad gene, say,or a childhood trauma—may not. After all, who’sto say that Spinoza’svaunted equanimity didn’tderive less from hisphilosophy than from hisbiology? Mightn’t agenetically programmedlow level of autonomic

arousal have produced hisserene philosophy, ratherthan the other wayaround?

Neurosesare generatednot only by incidentalindividual experiences,butalsoby the specificcultural conditionsunder which we live.… It is an individualfate, for example, to

have a domineering ora “self-sacrificing”mother, but it is onlyunder definite culturalconditions thatwe finddomineering or self-sacrificingmothers.—KARENHORNEY,TheNeuroticPersonalityofOurTime(1937)

I don’t have to look far

tofindevidenceofanxietyasafamilytrait.Mygreat-grandfather ChesterHanford, for many yearsthe dean of students atHarvard, was in the late1940sadmittedtoMcLeanHospital, the famousmental institution inBelmont, Massachusetts,suffering from acuteanxiety. The last thirtyyearsofhislifewereoften

agony.Thoughmedicationand electroshocktreatments wouldoccasionally bring aboutremissionsinhissuffering,such respites weretemporary, and in hisdarkest moments in the1960shewasreducedtoafetal ball in his bedroom,producing what myparents recall as aninhuman-sounding

moaning. Weighed downby the responsibility ofcaring for him, his wife,my great-grandmother, aformidable and brilliantwoman, died from anoverdose of scotch andsleepingpillsin1969.ChesterHanford’s son is

my maternal grandfather.Now ninety-three yearsold, he is an extremelyaccomplishedandgraceful

man—one of the sanestpeopleIknow.Butonecanperhapsseeshadowsoftheobsessions and the ritualsthat plagued his father.Forinstance,whenleavinga building, he will exitonly by way of the doorthroughwhichheentered,a superstition thatsometimes leads tocomplex logisticalmaneuverings.Mymother,

in turn, is a high-strungand inveterate worrierand,thoughsheenjoyedaproductive career as anattorney, suffers frommanyof the samephobiasandneurosesthatIdo.Sheassiduously avoids heights(glass elevators, chairlifts)and tends to avoid publicspeakingandrisktakingofmostkinds.Likeme,sheisalso mortally terrified of

vomiting. As a youngwoman, she suffered fromfrequent and severe panicattacks. At her mostanxious (or so my father,her ex-husband, insists),her fears verged onparanoia: when I was aninfant,myfathersays, shebecame convinced that aserial killer in a yellowVolkswagen was watchingour apartment.§ My only

sibling, a younger sister,struggleswithanxietythatis different frommine butnonetheless intense. She,too,hastakenCelexa—andalsoProzacandWellbutrinand Nardil and NeurontinandBuSpar.Noneofthemworked forher,and todayshemaybeoneofthefewadult members of mymother’ssideofthefamilynot currently taking a

psychiatric medication.(Variousotherrelativesonmymother’ssidehavealsorelied on antidepressantsand antianxietymedications continuouslyformanyyears.)On the evidence of just

these four generations onmy mother’s side (andthere is a separatecomplement ofpsychopathology coming

downtomeonthesideofmy father, who drankhimself intounconsciousness fivenights out of every seventhroughout much of mylater childhood), it is notoutlandish to concludethat I possess a geneticpredisposition to anxietyanddepression.But these facts, by

themselves, are not

dispositive—because is itnot possible that thebequeathing of anxietyfromonegenerationtothenext on my mother’s sidehad nothing to do withgenesandeverythingtodowith the environment? Inthe 1920s, my great-grandparents had a youngchild who died of aninfection. This wasdevastating to them.

Perhaps this trauma,combined with the latertraumaofhavingmanyofhis students die in WorldWar II, cracked somethingin my great-grandfather’spsyche—and, for thatmatter, in mygrandfather’s. Mygrandfather was inelementary school at thetimeofhisbrother’sdeathand can remember sitting

alongside the tiny casketas thehearsedrove to thecemetery. Perhaps mymother, in turn, acquiredher own anxieties byexperiencing the anxiousministrations of herworrywart mother; thepsychologicaltermforthisis “modeling.” Andperhaps I, observing mymother’s phobias, adoptedthem as my own. While

there is substantialevidence that specificphobias—particularlythose based on fears thatwould have been adaptivein the stateofnature, likephobias of heights orsnakes or rodents—aregenetically transmittable,or “evolutionarilyconserved,” isn’t it just asplausible, if not more so,to conclude that I learned

to be fearful by watchingmy mother be fearful? Orthat the generallyunsettled nature of mychildhood psychologicalenvironment—mymother’s constant anxiousbuzzing, my father’salcoholic absence, theunhappy tumult of theirmarriage that would endin divorce—produced inmeacomparablyunsettled

sensibility? Or that mymother’s paranoia andpanicwhilepregnantwithme produced suchhormonal Sturm undDrang in thewomb that Iwas doomed to be bornnervous? Researchsuggeststhatmotherswhosuffer stress whilepregnant are more likelyto produce anxiouschildren.‖ThomasHobbes,

the political philosopher,was born prematurelywhen hismother, terrifiedby the news that theSpanish Armada wasadvancing toward Englishshores, went into laborearly in April 1588.“Myself and fear wereborn twins,” Hobbeswrote, and he attributedhis own anxioustemperament to his

mother’s terror-inducedpremature labor. PerhapsHobbes’s view that apowerful state needs toprotect citizens from theviolence and misery theynaturally inflict on oneanother (life, he famouslysaid, isnasty,brutish,andshort)was foundedon theanxious temperamentimbuedinhiminuterobyhis mother’s stress

hormones.Or do the roots of myanxiety lie deeper andbroader than the thingsI’ve experienced and thegenes I’ve inherited—thatis, in history and inculture? My father’sparents were Jews whoemigrated from WeimarGermanyinthe1930s.Myfather’s mother became anastily anti-Semitic Jew—

she renounced herJewishnessoutoffearthatshe would someday bepersecuted for it. Myyounger sister and I wereraised in the EpiscopalChurch, our Jewishbackground hidden fromus until I was in college.Myfather,forhispart,hashad a lifelong fascinationwith World War II, andspecificallywiththeNazis;

he watched the televisionseries The World at Waragain and again. In mymemory, that program,with its stentorian musicaccompanying the Naziadvance on Paris, is therunningsoundtracktomyearlychildhood.aThelong-persecutedJews,ofcourse,have millennia ofexperience in havingreason to be scared—

which perhaps explainswhy some studies haveshown that Jewish mensufferfromdepressionandanxiety at rates higherthan men in other ethnicgroups.bMy mother’s cultural

heritage, on the otherhand, was heavily WASP;she is a proud Mayflowerdescendant who untilrecently subscribed

wholeheartedly to thenotion that there is noemotion and no familyissue that should not besuppressed.Thus, me: a mixture of

Jewish and WASPpathology—aneuroticandhistrionic Jew suppressedinside a neurotic andrepressed WASP. Nowonder I’m anxious: I’mlike Woody Allen trapped

inJohnCalvin.Or is my anxiety, afterall, “normal”—a naturalresponse to the times welive in? I was in middleschoolwhenTheDayAfter,about the dystopianaftermath of a nuclearattack, aired on networktelevision. As anadolescent, Iregularlyhaddreams that ended with amissilestreakingacrossthe

sky. Were these dreamsevidence of anxiouspsychopathology? Or areasonable reaction to theconditions I perceived—which were, after all, thesame conditions thatpreoccupieddefensepolicyanalysts through the1980s? The Cold War, ofcourse,hasnowlongsinceended—but it has beenreplaced by the threat of

hijacked airplanes, dirtybombs, underwearbombers,chemicalattacks,and anthrax, not tomention SARS, swine flu,drug-resistanttuberculosis,the prospect of climate-change-induced globalapocalypse, and theabiding stresses of aworldwide economicslowdown and of a globaleconomy undergoing

seemingly constantupheaval. Insofar as it’spossible to measure suchthings, eras of socialtransformation seem toproduce a quantumincrease in the anxiety ofthe population. In ourpostindustrial era ofeconomic uncertainty,wheresocialstructuresareundergoing continuousdisruption and where

professional and genderroles are constantlychanging, is it not normal—adaptive even—to beanxious?At some level, yes, it is

—at least to the extentthat it is always, or often,adaptive to be reasonablyanxious. According toCharles Darwin (whohimself suffered fromcripplingagoraphobia that

left him housebound foryears after his voyage onthe Beagle), species that“fear rightly” increasetheir chances of survival.Weanxiouspeoplearelesslikely to remove ourselvesfromthegenepoolby,say,frolicking on the edge ofcliffs or becoming fighterpilots.An influential studyconductedahundredyears

ago by two Harvardpsychologists, Robert M.Yerkes and JohnDillingham Dodson,demonstrated thatmoderate levels of anxietyimprove performance inhumans and animals: toomuch anxiety, obviously,and performance isimpaired, but too littleanxiety also impairsperformance. When the

use of antianxiety drugsexploded in the 1950s,some psychiatrists warnedabout the dangerspresentedbyasocietythatwas not anxious enough.“Wethenfacetheprospectof developing a falselyflaccid race of peoplewhich might not be toogood for our future,” onewrote.Anotherpsychiatristaverred that “Van Gogh,

IsaacNewton:most of thegeniusesandgreatcreatorswere not tranquil. Theywere nervous, ego-drivenmen pushed on by arelentless inner force andbesetbyanxieties.”Ismuting such genius a

price society would haveto pay for drasticallyreducing anxiety,pharmacologically orotherwise?Andwouldthat

costbeworthwhile?“Without anxiety, little

would be accomplished,”says David Barlow, thefounder and directoremeritus of the Center forAnxiety and RelatedDisorders at BostonUniversity. “Theperformance of athletes,entertainers, executives,artisans, and studentswould suffer; creativity

would diminish; cropsmightnotbeplanted.Andwewould all achieve thatidyllic state long soughtafter in our fast-pacedsociety of whiling awayour lives under a shadetree. This would be asdeadly for the species asnuclearwar.”

I have come to believethat anxiety

accompaniesintellectual activity asitsshadowandthatthemore we know of thenature of anxiety, themore we will know ofintellect.—HOWARDLIDDELL,“THEROLEOFVIGILANCEINTHEDEVELOPMENTOF

ANIMALNEUROSIS”(1949)

Some eighty years ago,Freud proposed thatanxiety was “a riddlewhose solution would bebound to throwa floodoflightonourwholementalexistence.” Unlocking themysteries of anxiety, hebelieved, would go far inhelping us to unravel themysteries of the mind:consciousness, the self,identity, intellect,

imagination, creativity—not to mention pain,suffering,hope,andregret.To grapple with andunderstand anxiety is, insome sense, to grapplewith and understand thehumancondition.The differences in how

various cultures and erashave perceived andunderstoodanxietycantellus a lot about those

culturesanderas.Whydidthe ancient Greeks of theHippocratic school seeanxiety mainly as amedical condition, whilethe Enlightenmentphilosophers saw it as anintellectual problem?Whydidtheearlyexistentialistssee anxiety as a spiritualcondition, while GildedAge doctors saw it as aspecifically Anglo-Saxon

stress response—aresponse that theybelieved spared Catholicsocieties—totheIndustrialRevolution? Why did theearlyFreudiansseeanxietyas a psychologicalcondition emanating fromsexual inhibition, whereasour own age tends to seeit,onceagain,asamedicaland neurochemicalcondition, a problem of

malfunctioningbiomechanics?Do these shiftinginterpretations representthe forward march ofprogress and science? Orsimply the changing, andoften cyclical, ways inwhich cultures work?Whatdoesitsayaboutthesocieties in question thatAmericans showing up inemergency rooms with

panic attacks tend tobelieve they’re havingheart attacks, whereasJapanesetendtobeafraidthey’regoingtofaint?AretheIranianswhocomplainof what they call “heartdistress” suffering whatWestern psychiatristswould call panic attacks?Are the ataques de nerviosexperienced by SouthAmericans simply panic

attacks with a Latinoinflection—or are they, asmodern researchers nowbelieve, a distinct culturaland medical syndrome?Why do drug treatmentsfor anxiety that work sowellonAmericansandtheFrench seem not to workeffectivelyontheChinese?As fascinating and

multifarious as thesecultural idiosyncrasiesare,

theunderlyingconsistencyof experience across timeand cultures speaks to theuniversalityofanxietyasahuman trait. Even filteredthrough the distinctivecultural practices andbeliefs of the GreenlandInuitahundredyearsago,the syndrome the Inuitcalled“kayakangst”(thoseafflicted by it were afraidto go out seal hunting

alone) appears to be littledifferent from what wetoday call agoraphobia. InHippocrates’s ancientwritings can be foundclinical descriptions ofpathological anxiety thatsound quite modern. Oneof his patients wasterrified of cats (simplephobia, which todaywouldbecoded300.29forinsurance purposes,

according to theclassifications of the fifthedition of the Diagnosticand Statistical Manual, theDSM-V) and another ofnightfall; a third,Hippocrates reported, was“besetbyterror”wheneverhe heard a flute; a fourthcould not walk alongside“even the shallowestditch,” though he had noproblemwalkinginsidethe

ditch—evidence of whatwe would today callacrophobia, the fear ofheights. Hippocrates alsodescribes a patientsuffering what wouldlikelybecalled,inmoderndiagnostic terminology,panic disorder withagoraphobia (DSM-V code300.22): the condition, asHippocrates described it,“usually attacks abroad, if

a person is travelling alonely road somewhere,and fear seizes him.” Thesyndromes described byHippocrates arerecognizably the sameclinical phenomenadescribed in the latestissues of the Archives ofGeneral Psychiatry andBulletin of the MenningerClinic.Their similarities bridge

the yawning gap ofmillennia andcircumstances thatseparatethem,providingasense of how, for all thedifferences in culture andsetting,thephysiologicallyanxious aspects of humanexperience may beuniversal.

Inthisbook,Ihavesetout

to explore the “riddle” ofanxiety.Iamnotadoctor,a psychologist, asociologist, or a historianof science—any one ofwhom would bring morescholarly authority to atreatise on anxiety than Ido. This is a work ofsynthesis and reportage,yoking togetherexplorationsof the ideaofanxiety from history,

literature, philosophy,religion, popular culture,and the latest scientificresearch—all of thatwoven through somethingabout which I can, alas,claim extensive expertise:my own experience withanxiety. Examining thedepthsofmyownneurosesmay seem the height ofnarcissism (and studies doshow that self-

preoccupation tends to betiedtoanxiety),butit’sanexercise with worthyantecedents. In 1621, theOxford scholar RobertBurton published hiscanonical The Anatomy ofMelancholy, a staggeringthirteen-hundred-pagework of synthesis, whosetorrents of scholarlyexegesis only partiallyobscurewhatitreallyis:a

massive litany of anxious,depressive complaint. In1733, George Cheyne, aprominent Londonphysician and one of themost influentialpsychological thinkers ofthe eighteenth century,published The EnglishMalady, which includesthe forty-page chapter“The Case of the Author”(dedicated to “my fellow

sufferers”), in which hereportsinminutedetailonhis neuroses (including“Fright, Anxiety, Dread,and Terror” and “amelancholy Fright andPanick, where my ReasonwasofnoUsetome”)andphysical symptoms(including “a suddenviolent Head-ach,”“extream Sickness in myStomach,”and“aconstant

Colick,andanillTasteandSavour in my Mouth”)over the years. Morerecently, the intellectualodysseys of CharlesDarwin, Sigmund Freud,and William James werepowerfullydrivenby theircuriosity about, and thedesire to find relief from,their own anxioussuffering. Freud used hisacute trainphobiaandhis

hypochondria, amongother things, to constructhis theory ofpsychoanalysis; Darwinwas effectivelyhousebound by stress-related illnesses after thevoyage of the Beagle—hespent years in pursuit ofrelief from his anxiety,visiting spas and, on theadvice of one doctor,encasing himself in ice.

James tried to keep hisphobias hidden from thepublic but was oftenquietly terrified. “I awokemorning after morningwith a horrible dread inthepitofmystomachandwith a sense of insecurityof life that I never knewbefore,” hewrote in 1902oftheonsetofhisanxiety.“Formonths, Iwasunableto go out in the dark

alone.”Unlike Darwin, Freud,

and James, I’m not out toadumbrate a whole newtheory of mind or ofhumannature.Rather,thisbook is motivated by aquest to understand, andto find relief from orredemption in, anxioussuffering. This quest hastaken me both backward,into history, and forward,

to the frontiers ofmodernscientific research. I havespent much of the pasteight years readingthrough hundreds ofthousands of the pagesthat have been writtenaboutanxietyoverthelastthreethousandyears.My life has, thankfully,

lacked great tragedy ormelodrama. I haven’tserved any jail time. I

haven’t been to rehab. Ihaven’t assaulted anyoneor carried out a suicideattempt. I haven’t wokenupnaked in themiddleofa field, sojourned in acrack house, or been firedfrom a job for erraticbehavior. Aspsychopathologies go,mine has been—so far,most of the time, tooutward appearances—

quiet. Robert Downey Jr.will not be starring in themovieofmy life. I am, asthey say in the clinicalliterature, “highfunctioning” for someonewithananxietydisorderora mental illness; I’musually quite good athidingit.Morethanafewpeople, some of whomthink they knowme quitewell, have remarked that

theyarestruckthatI,whocan seem so even-keeledand imperturbable, wouldchoose to write a bookabout anxiety. I smilegently while churninginside and thinking aboutwhat I’ve learned is asignature characteristic ofthe phobic personality:“theneedandability”—asdescribed in the self-helpbook Your Phobia—“to

presentarelativelyplacid,untroubled appearance toothers, while sufferingextreme distress on theinside.”cTo some people, I may

seem calm. But if youcould peer beneath thesurface, you would seethat I’m like a duck—paddling, paddling,paddling.

The chief patient I ampreoccupied with ismyself.—SIGMUNDFREUDTOWILHELMFLIESS(AUGUST

1897)

It has occurred to methat writing this bookmightbeaterribleidea:ifit’s relief from nervoussufferingthatIcrave,then

burrowing into thehistoryandscienceofanxiety,andinto my own psyche, isperhaps not the best waytoachieveit.In my travels through

the historical literature onanxiety, I came across alittle self-help book by aBritish army veterannamed Wilfrid Northfield,who suffered nervousprostrationduringtheFirst

WorldWarandthenspentten years largelyincapacitated by anxietybefore successfullyconvalescing and writinghis guide to recovery.Published in 1933,Conquest of Nerves: TheInspiring Record of aPersonal Triumph overNeurasthenia, became abestseller;thecopyIhaveis from the sixth printing,

in 1934. In his lastchapter, “A Few FinalWords,” Northfield writes:“There is one thing theneurasthenic must guardagainst very strongly, andthat is talking about histroubles. He can get nocomfortorassistanceinsodoing.”Northfieldgoeson:“To talk of troubles in avoluble, despairing way,merely piles on the agony

and ‘plays-up’ theemotions.Notonlyso,butit is selfish.” Citinganother author, heconcludes:“‘Neverdisplaya wound, except to aphysician.”Never display a wound.

Well, after more thanthirtyyearsofendeavoring—successfullymuchofthetime—to conceal myanxietyfrompeople,hereI

amputtingitonprotractedexhibition foracquaintances andstrangers alike. IfNorthfield is correct (andmyworriedmotheragreeswithhim),thisprojectcanhardly be auspicious formy mental health.Elements of modernresearch lend support toNorthfield’s warning:anxious people have a

pathological tendency tofocus their attentioninward, on themselves, ina way that suggests abook-length dwelling onone’s own anxiety ishardly the best way toescapeit.dMoreover, one concern

I’vehadaboutwritingthisbook is that I’ve subsistedprofessionally on myability toproject calmness

and control; my anxietymakes me conscientious(I’m afraid of screwingthings up), andmy shamecanmakeme seempoised(I need to hide that I’manxious). A formercolleague once describedme as “human Xanax,”telling me, as I chuckledinwardly, that I projectsuch equanimity that mymere presence can be

calming to others: simplytowalkintoaroomfullofagitated people is toadminister my soothingbalm; people relax in mywake.Ifonlysheknew!Byrevealing the fraudulenceofmyputative calm,am Iforfeiting my ability tosoothe others and therebycompromising myprofessionalstanding?Mycurrenttherapist,Dr.

W., says there is alwaysthe possibility thatrevealing my anxiety willlift the burden of shameandreducetheisolationofsolitary suffering. When Iget skittish about airingmy psychiatric issues in abook,Dr.W.says:“You’vebeenkeepingyouranxietya secret for years, right?How’sthatworkingoutforyou?”

Pointtaken.Andthereisa rich and convincingliterature about how—contrary to theadmonitions of WilfridNorthfield (and mymother)—hiding orsuppressing anxietyactually produces moreanxiety.e But there is noescaping my concern thatthis exercise is not onlyself-absorbedandshameful

but risky—that it willprove the Wile E. CoyotemomentwhenIlookdowntodiscoverthat,insteadofinner strengths or outerbuttresses to support me,there is in fact nothing tostopmefromfallingalongwaydown.

I know how indecentand shocking Egotismis, and for an Author

to make himself theSubjectofhisWordsorWorks, especially in sotedious andcircumstantiated aDetail: But … Ithought … perhaps itmay not be quiteuseless to some lowdespondingvaletudinary, over-grown Person, whoseCase may have some

Resemblancetomine.—GEORGECHEYNE,TheEnglishMalady(1733)

“Why,”Dr.W.asks,“doyou think writing aboutyour anxiety in a bookwouldbesoshameful?”Because stigma still

attaches to mental illness.Because anxiety is seen asweakness. Because, as the

signspostedonAlliedguninstallations in Maltaduring World War II sobluntlyputit,“ifyouareaman you will not permityour self-respect to admitan anxiety neurosis or toshow fear.” Because Iworry that thisbook,withits revelations of anxietyand struggle, will be alitany of Too MuchInformation,aviolationof

basicstandardsofrestraintanddecorum.fWhen I explain this to

Dr. W., he says that theveryactofworkingonthisbook,andofpublishingit,could be therapeutic. Inpresenting my anxiety tothe world, he says, I willbe “coming out.” Theimplicationisthatthiswillbe liberating, as though Iwere gay and coming out

ofthecloset.Butbeinggay—we now finally know(homosexuality wasclassified as a mentaldisorder by the AmericanPsychiatric Associationuntil 1973)—is not aweaknessoradefectoranillness. Being excessivelynervousis.

For a long time, governed

by reticence and shame, Ihad told people whoinquired about my bookthat itwas“aculturalandintellectual history ofanxiety”—true,as faras itgoes—without revealingits personal aspects. But alittle while ago, in aneffort to test theeffectsof“comingout”asanxious, Ibegan gingerly to speakmore forthrightly about

what the bookwas about:“aculturalandintellectualhistory of anxiety, woventogether by my ownexperienceswithanxiety.”The effect was striking.When I had spoken aboutthe book as arid history,peoplewouldnodpolitely,and a few wouldbuttonhole me privatelylater to ask me specificquestions about this or

thataspectofanxiety.ButasIstartedtoacknowledgethe personal parts of thebook, I found myselfsurrounded by avidlisteners, eager to tell meabout their own, or theirfamilymembers’,anxiety.One night I attended adinner with a bunch ofwriters and artists.SomeoneaskedwhatIwasworking on, and I

deliveredmynewspiel(“acultural and intellectualhistory of anxiety, woventogether and animated bymy own experiences withanxiety”), talking aboutsome of my experienceswith various antianxietyand antidepressantmedications. To myastonishment, each of theother nine people withinearshot responded by

telling me a story abouthis or her own experiencewith anxiety andmedication.g Around thetablewewent,sharingourtalesofneuroticwoe.hI was struck that

admittingmyownanxietyover dinner had dislodgedsuch an avalanche ofpersonal confessions ofanxiety andpharmacotherapy.

Granted, I was with abunch of writers andartists, a populationostensibly more prone, asobservers since Aristotlehave noted, to variousforms of mental illnessthan other people. Somaybethesestoriessimplyprovide evidence thatwriters are crazy. Ormaybe the stories areevidence that the

pharmaceutical companieshave succeeded inmedicalizing a normalhuman experience andmarketingdrugs to “treat”it.iButmaybemorepeoplethan I thought arestrugglingwithanxiety.“Yes!”saidDr.W.when

Iventuredthispropositionat my next session withhim. Then he told me astory of his own: “My

brother used to hostregular salon evenings,where people would beinvited in to lecture onvarioustopics.Iwasaskedto give a talk on phobias.After my lecture, everysingle one of the peoplethere came up to tell meabout their phobias. Ithinktheofficialnumbers,as high as they are,underreport.”

After he told me this, Ithought about Ben, mybest friend fromcollege,arich and successful writer(he regularly graces thebest-seller lists and box-office charts), whosedoctor had recentlyprescribed him Ativan, abenzodiazepine,tocombattheanxioustightnessinhischest that had himconvincedhewassuffering

a heart attack.j And Ithought of Ben’s neighborM., a multimillionairehedge fundmanager,whotakesXanax constantly forhis panic attacks. And ofmyformercolleagueG.,aneminent politicaljournalist, who in theyearssinceendingupinanemergency room after apanic episode has beentaking various

benzodiazepinestopreventfurther attacks. And ofanother former colleague,B.,whoseanxiety lefthimstammering in meetingsand unable to completework projects until hewentonLexapro.No, not everyone gets

overwhelmed by anxiety.Mywife,forone,doesnot.(Thank God.) BarackObama, by all accounts,

does not. Nor, evidently,does David Petraeus, theformercommanderofU.S.forces in Afghanistan andformerdirectoroftheCIA:he once told a reporterthat despite being in jobswhere the day-to-daystakes are amatter of lifeanddeath,he“rarelyfeelsstress at all.”k All-Proquarterbacks like TomBradyandPeytonManning

manifestly do not, at leastnot on the field.l One ofthethingsIexploreinthisbook is why some peopleare preternaturally calm,exhibiting grace evenunder tremendouspressure, while others ofussuccumbtopanicatthemildesthintofstress.Yet enough of us dosuffer from anxiety thatperhaps writing about my

own ought not to be anoccasion for shamebutanopportunity to providesolace to some of themillions of others whoshare this affliction. Andmaybe, as Dr. W. oftenreminds me, the exercisewill be therapeutic. “Youcan write yourself tohealth,”hesays.Still, I worry. A lot. It’smy nature. (Besides, as

many people have said tome, how can you not beanxious writing a bookaboutanxiety?)Dr.W.,forhispart,says:

“Put your anxiety aboutthebookintothebook.”

The planning functionof the nervous system,in the course ofevolution, hasculminated in the

appearance of ideas,values,andpleasures—the uniquemanifestationsofman’ssocial living. Man,alone,canplanfor thedistant future,andcanexperience theretrospective pleasuresof achievement. Man,alone, can be happy.Butman,alone,canbeworriedandanxious.

—HOWARDLIDDELL,“THEROLEOFVIGILANCEINTHEDEVELOPMENTOF

ANIMALNEUROSIS”(1949)

In all the insights intohistory and culture that astudy of anxiety mightproduce, is there anythingthat can help theindividual anxietysufferer? Canwe—can I—

reduceanxiety,orcometoterms with it, byunderstanding the valueandmeaningofit?I hope so. But when I

have a panic attack, thereis nothing interestingabout it. I try to thinkabout it analytically and Ican’t—it’s just miserablyunpleasantandIwantittostop. A panic attack isinteresting the way a

broken leg or a kidneystoneisinteresting—apainthatyouwanttoend.Some years ago, before

embarkingontheresearchforthisprojectinearnest,Ipicked up an academicbookaboutthephysiologyofanxietytoreadwhileonaflightfromSanFranciscotoWashington,D.C.Asweflew smoothly over theWest, I was immersed in

thebookandfeltlikeIwasgaining an intellectualunderstanding of thephenomenon.So,IthoughtasIread,it’ssimplyaflurryof activity in my amygdalathat produces that acutelymiserable emotion Isometimes feel? Thosefeelings of doom and terrorare just the bubbling ofneurotransmitters in mybrain?Thatdoesn’t seem so

intimidating. Armed withthis perspective, Icontinued thinking: I canexert mind over matter andreduce the physicalsymptomsofanxietytotheirproper place—mere routinephysiology—and live morecalmly in the world. Here Iam,hurtlingalongat thirty-eight thousand feet,and I’mnoteventhatnervous.Then the turbulence

started. It wasn’tparticularly severe, but aswe bumped along abovethe Rockies, anyperspective orunderstanding I thought Ihad gained was renderedinstantly useless; my fearresponse revved up, anddespitegulpingXanaxandDramamine,Iwasterrifiedand miserable until welandedseveralhourslater.

Myanxietyisareminderthat Iamgovernedbymyphysiology—that whathappens in the body maydo more to determinewhathappens in themindthan the other wayaround. Though thinkersfrom Aristotle to WilliamJames to the researcherswho publish today in thejournal PsychosomaticMedicine have recognized

thisfact,itrunscountertoone of the basic Platonic-Cartesian tenets ofWesternthought—theideathatwhowe are, thewaywethinkandperceive,isaproduct of ourdisembodied souls orintellects. The brutebiological factness ofanxiety challenges oursense of who we are:anxietyremindsusthatwe

are,likeanimals,prisonersof our bodies, which willdecline and die and ceaseto be. (No wonder we’reanxious.)Andyetevenasanxietythrows us back into ourmost primitive, fight-or-flight-driven reptilianselves, it is also whatmakes usmore thanmereanimals. “If man were abeast or an angel,”

Kierkegaard wrote in1844, “he would not beabletobeinanxiety.Sinceheisbothbeastandangel,he can be in anxiety, andthegreatertheanxiety,thegreater the man.” Theability toworry about thefuture goes hand in handwiththeabilitytoplanforthe future—and planningfor the future (along withremembering the past) is

what gives rise to cultureand separates us fromotheranimals.For Kierkegaard, as for

Freud, the most anxiety-producing threats lay notintheworldaroundusbutrather deep inside us—inour uncertainty about theexistential choices wemake and in our fear ofdeath. Confronting thisfear, and risking the

dissolution of one’sidentity, expands the souland fulfills the self.“Learningtoknowanxietyis an adventure whicheverymanhastoaffrontifhe would not go toperdition either by nothaving known anxiety orby sinking under it,”Kierkegaard wrote. “Hethereforewho has learnedrightlytobeinanxietyhas

learned the mostimportantthing.”Learning rightly to be in

anxiety. Well, I’m trying.This book is part of thateffort.

* Seneca was also in some senseanticipating FDR’s famousformulation: “The only thing wehavetofearisfearitself.”

†Hippocratesbelieved that staying

in good physical and mentalhealth required maintaining theright balance of what he calledthefourhumors,orbodilyfluids:blood, phlegm, black bile, andyellow bile. A person’s relativehumoral balance accounted forhis temperament: whereassomeone with relatively moreblood might have a fierycomplexion and a lively or“sanguine” temperament and begiven to hot-blooded explosions

of temper, someone withrelatively more black bile mighthave swarthy skin and amelancholic temperament. Anoptimal mixture of the humors(eucrasia) produced a state ofhealth;whenthehumorsfellintodisequilibrium (dyscrasia), theresult was disease. ThoughHippocrates’s humoral theory ofmind is now discredited, itpersistedfortwothousandyears,until the 1700s, and it lives on

still in our use of words like“bilious” and “phlegmatic” todescribe people’s personalities—and in the biomedical approachto anxiety and mental illnessgenerally.

‡ Or someone who followed himdeclared.Most historians believethatwhathavecomedowntousas the so-called Hippocraticwritingswereinfactproducedbya number of doctors who werefollowersofHippocrates.Someof

thewritingsinthecorpusseemtodatefromafterhisdeathandarebelievedtohavebeenwrittenbyhis son-in-law Polybus;Hippocrates’s sons Draco andThessalus also became famousdoctors. For simplicity’s sake, ItreatHippocrates’swritingastheworkofoneman,sincethemodeof thinking that the writingsrepresentderivesfromhim.

§ Today, my mother and father,now divorced fifteen years,

disagreeabouttheseverityoftheparanoia:myfatherinsistsitwasconsiderable; my mother says itwas minor (and that, for thatmatter,therewasactuallyaserialkillerafootatthetime).

‖ One study found that childrenwhose mothers were pregnantwith them on September 11,2001, still had elevated levels ofstresshormones in theirbloodatsix months. Similar findings—showing as-yet-unborn children

acquiringhigherlifetimebaselinelevels of stressed-out physiology—havebeenreportedduringwarandotherchaotictimes.

a When my mother was attendinglawschoolatnight,mysisterandI would spend evenings mopingaroundthehousewhilemyfatherplayedBach fugueson thepianoand then parked himself with abowl of popcorn and a bottle ofgininfrontofTheWorldatWar.

b There’s also evidence that the

highIQscoresofAshkenaziJewsareattachedsomehowtothehighanxietyratesof thatsamegroup,and there are plausibleevolutionary explanations forwhy both intelligence andimaginationtendtobealliedwithanxiety. (Various studies havefound that the average IQ ofAshkenazi Jews is eight pointshigher than that of the nexthighest ethnic group, NortheastAsians, and close to a full

standard deviation higher thanotherEuropeangroups.)

c “For many, many people whohave anxiety disorders—particularly agoraphobia andpanic disorder—peoplewould besurprised to find out that theyhave problems with anxietybecause they seem so ‘together’and in control,” says PaulFoxman, a psychologist whoheads the Center for AnxietyDisordersinBurlington,Vermont.

“They seem to be comfortable,but there’s a disconnectionbetween the public self and theprivateself.”

d David Barlow, one of thepreeminent researchers in thefield, notes (in the jargon-intensive terminology of thespecialist) that pathological,negative self-focus “seems to bean integralpart of the cognitive-affective structure of anxiety.This negative self-evaluative

focus and disruption of attentionis in large part responsible fordecreases in performance. Thisattentionshiftinturncontributesto a vicious cycle of anxiousapprehension, in whichincreasing anxiety leads tofurther attentional shifts,increased performance deficits,and subsequent spiraling ofarousal.”

e On the desk in front of me is a1997 article from the Journal of

Abnormal Psychology called“Hiding Feelings: The AcuteEffectsofInhibitingNegativeandPositiveEmotions.”

f As I write this, I can hear thestrainsofwhatmaybemybetterjudgment: Even if you are sounfortunate as to be excessivelyanxious, at least have the dignitynot to prattle on about it publicly.Keepastiffupperlip,andkeepittoyourself.

g For instance, S., a nonfiction

writer in hermidthirties, told oftaking Xanax and Klonopin forher anxiety and about how sheswitched fromProzac toLexaprobecause Prozac had killed herlibido. C., a poet in hismidforties, said that he’d had totaketheantidepressantZoloftforpanic attacks. (C.’s first panicattack had landed him in theemergency room, convinced hewas having a heart attack.Subsequent attacks, he said,

“were not so bad because youknowwhat theyare—but they’restill scary because you alwayswonder, Maybe this time I reallyam having a heart attack.” Someepidemiological surveys havefound that one-third of adultssuffering their first panic attackend up in the emergency room.)K.,anovelist,saidthatwhileshewastryingtofinishherlastbook,her anxiety got so bad that shecouldn’t work. Fearing she was

going crazy, she went to herpsychiatrist, who prescribed herZoloft, which made her fat, andthen Lexapro, which increasedher anxiety so much that shecouldnolongerevenbeartopickherchildrenupatschool.

h After dinner, yet another writerapproached me. The woman—let’s call her E.—is a globe-trotting war correspondent andbest-selling author in her latethirtieswhosuffers, she toldme,

from a litany of depressive,anxious symptoms (includingtrichotillomania, a disorder thatcausespeople,mainlywomen, tocompulsively pull their hair outwhen under stress), for which adoctor had prescribed her theantidepressant Lexapro. Imarveled that E., despite heranxiety and depression, hadmanaged to travel all aroundAfricaandtheMiddleEast,filingdispatches from war-ravaged

countries, often at great risk toher personal safety; for me,simplytravelingmorethanafewmiles from home can bemiserably anxiety producing andbowelloosening.“Ifeelcalmerinwarzones,”shesaid.“Iknowit’sperverse, but I feel more calmwhile being shelled; it’s one ofthe few times I don’t feelanxiety.”Waitingforaneditortomakeajudgmentaboutanarticleshe’s submitted, however, can

send her spiraling into anxietyand depression. (Freud observedthat threats toour self-esteemorself-conception can often causefar more anxiety than threats toourphysicalwell-being.)

i There is definitely some truth tothat,and Iwillhavea lot to sayabout the topic in part3 of thisbook.

j Even thoughBennow travels theworldandwalks red carpets andcommands tens of thousands of

dollars for a speech, I can stillremember the times, in the leanyears before his first book cameout, when he would getoverwhelmed by panic attacks ifwe strayed too far from hisapartmentandwhentheprospectof socializing at a party wouldleave him so nervous he’d vomitinto the bushes outsidebeforehand.

k Perhaps he would have beenbetter off feeling more stress—a

greater intensity of worry aboutconsequences might haveprevented the adulterousmisadventure that led to hisdownfall.

l Not that coolness and toughnesson the field are guarantees ofequanimity off of it. TerryBradshaw, the Steelers Hall ofFame quarterback from the late1970s, was a fearless gladiatorwhowentontobedebilitatedbydepressionandpanicattacks.Earl

Campbell, the burly, fearsomeHouston Oilers running backfromthe1970s, foundhimself,adecade later, housebound bypanicattacks.

CHAPTER2

WhatDoWeTalkAboutWhenWeTalkAboutAnxiety?

Although it is widelyrecognizedthatanxiety

is the most pervasivepsychologicalphenomenon of ourtime… there has beenlittle or no agreementon its definition, andvery little, if any,progress on itsmeasurement.—PAULHOCH,PRESIDENT,

AMERICANPSYCHOPATHOLOGICAL

ASSOCIATION,INANADDRESSTOTHEFIRST-EVERACADEMIC

CONFERENCEONANXIETY

(1949)

For researchers aswellas laymen, this is theage of anxiety … .[But] can we honestlyclaim that ourunderstanding ofanxiety has increased

in proportion to thehuge research effortexpended or evenincreasedperceptibility?Wethinknot.—“THENATUREOFANXIETY:AREVIEWOFTHIRTEENMULTIVARIATEANALYSESCOMPRISING814

VARIABLES,”PsychiatricReports(DECEMBER

1958)

Anxiety isnotasimplethingtograsp.—SIGMUNDFREUD,TheProblemofAnxiety

(1926)

On February 16, 1948, at3:45 in the afternoon, mygreat-grandfather Chester

Hanford,whohadrecentlysteppeddownaftertwentyyears as the dean ofHarvard College toconcentrate full-time onhis academic work as aprofessor of government(“withafocusonlocalandmunicipalgovernment,”ashe liked to say), wasadmitted to McLeanHospitalwithaprovisionaldiagnosis of

“psychoneurosis” and“reactive depression.”Fifty-six years old at thetime of his admission,Chester reported that hisprimary complaints wereinsomnia, “feelings ofanxiety and tension,” and“fears as to the future.”Described by the hospitaldirector as a“conscientious and usuallyvery effective man,”

Chesterhadbeeninastateof “anxiety of a rathersevere degree” for fivemonths. The night beforepresenting himself atMcLean, he had told hiswife that he wanted tocommitsuicide.Thirty-one years later,

on October 3, 1979, at8:30 in the morning, myparents—worried that I,ten years old and in the

fifth grade, had of latebeen piling variousalarming new tics andbehavioral oddities on topof my already obsessivegerm avoidance and acuteseparation anxiety andphobia of vomiting—tookmetothesamepsychiatrichospitaltobeevaluated.Ateam of experts (apsychiatrist, apsychologist, a social

worker,andseveralyoungpsychiatric residents whosat hidden behind a two-way mirror and watchedme get interviewed andtake a Rorschach test)diagnosed me with“phobic neurosis” and“overanxious reactiondisorderofchildhood”andobserved that I would beat significant risk ofdeveloping “anxiety

neurosis” and “neuroticdepression” as I got olderifIwasn’ttreated.Twenty-five years after

that,onApril13,2004,attwo o’clock in theafternoon, I, now thirty-fouryearsoldandworkingas a senior editor at TheAtlantic magazine anddreadingthepublicationofmy first book, presentedmyself at the nationally

renowned Center forAnxiety and RelatedDisorders at BostonUniversity. After meetingfor several hours with apsychologist and twograduate students andfillingoutdozensofpagesof questionnaires(including, I later learned,the Depression AnxietyStressScalesandtheSocialInteraction Anxiety Scale

and the Penn StateWorryQuestionnaire and theAnxiety Sensitivity Index),I was given a principaldiagnosis of “panicdisorder withagoraphobia” andadditional diagnoses of“specific phobia” and“social phobia.” Theclinicians also noted intheir report that myquestionnaire scores

indicated “mild levels ofdepression,” “strong levelsof anxiety,” and “stronglevelsofworry.”Why so many different

diagnoses? Did the natureof my anxiety change somuch between 1979 and2004?Andwhydidn’tmygreat-grandfather and Ireceive the samediagnoses?Asdescribedinhis case files, the general

scopeofChesterHanford’ssyndrome was awfullysimilar to mine. Were my“strong levels of anxiety”reallysodifferentfromthe“feelings of anxiety andtension” and “fears as tothe future” that afflictedmygreat-grandfather?Andanyway, who, aside fromthe most well adjusted orsociopathic among us,doesn’t have “fears as to

the future” or suffer“feelings of anxiety andtension”? What, ifanything, separates theostensibly “clinically”anxious, like my great-grandfather and me, fromthe “normally” anxious?Aren’tweall,consumedbythegetting and strivingofmoderncapitalistsociety—indeed, as a consequenceof being alive, subject

always to the caprice andviolence of nature andeach other and to theinevitability of death—atsome level“psychoneurotic”?Technically, no; in fact,

no one is anymore. Thediagnoses that ChesterHanford received in 1948nolongerexistedby1980.And the diagnoses that Ireceivedin1979nolonger

existtoday.In 1948,

“psychoneurosis” was theAmerican PsychiatricAssociation’s term forwhat that organizationwould, with theintroductionin1968ofthesecond edition ofpsychiatry’s bible, theDiagnostic and StatisticalManual (DSM-II), officiallydesignate as simply

“neurosis”andwhatithas,since the introduction ofthe third edition (DSM-III)in 1980, called “anxietydisorder.”*This evolving

terminology mattersbecausethedefinitions—aswell as the symptoms, therates of incidence, thepresumed causes, theculturalmeanings,andtherecommended treatments

—associated with thesediagnoses have changedalong with their namesovertheyears.Thespeciesofunpleasantemotionthattwenty-five hundred yearsago was associated withmelaina chole (ancientGreekfor“blackbile”)hassince also been described,in sometimes overlappingsuccession, as“melancholy,” “angst,”

“hypochondria,”“hysteria,” “vapors,”“spleen,” “neurasthenia,”“neurosis,”“psychoneurosis,”“depression,” “phobia,”“anxiety,” and “anxietydisorder”—and that’sleaving aside suchcolloquial terms as panic,worry, dread, fright,apprehension, “nerves,”“nervousness,” “edginess,”

“wariness,” “trepidation,”“jitters,” “willies,”“obsession,” “stress,” andplainold“fear.”Andthat’sjust in English, where theword “anxiety”was rarelyfound in standardpsychological or medicaltextbooksinEnglishbeforethe 1930s, whentranslators beganrendering the GermanAngst (as deployed in the

works of Sigmund Freud)as“anxiety.”†Which raises the

question: What are wetalking about when wetalkaboutanxiety?The answer is not

straightforward—or,rather, it depends onwhom you ask. For SørenKierkegaard,writinginthemid-nineteenth century,anxiety (angst in Danish)

was a spiritual andphilosophical problem, avague yet inescapableuneasiness with noobvious direct cause.‡ ForKarl Jaspers, the Germanphilosopher andpsychiatristwhowrotetheinfluential 1913 textbookGeneral Psychopathology, itwas“usually linkedwithastrong feeling ofrestlessness…afeelingthat

one has … not finishedsomething; or… that onehas to look for somethingor… come into the clearabout something.” HarryStack Sullivan, one of themost prominent Americanpsychiatrists of the firsthalf of the twentiethcentury,wrotethatanxietywas “that which oneexperiences when one’sself-esteem is threatened”;

Robert Jay Lifton, one ofthe most influentialpsychiatrists of the secondhalf of the twentiethcentury, similarly definesanxiety as “a sense offoreboding stemming froma threat to the vitality oftheself,or,moreseverely,from the anticipation offragmentationof the self.”ForReinholdNiebuhr, theCold War–era theologian,

anxiety was a religiousconcept—“the internalprecondition of sin… theinternal description of thestate of temptation.” Fortheir part, manyphysicians—starting withHippocrates (in the fourthcenturyB.C.)andGalen(inthe second centuryA.D.)—have argued that clinicalanxiety is a

straightforward medicalcondition, an organicdisease with biologicalcauses as clear, or nearlyso,asthoseofstrepthroatordiabetes.Then there are thosewho say that anxiety isuseless as a scientificconcept—that it is animprecise metaphorstraining to describe aspectrum of human

experiencetoobroadtobecaptured with a singleword.In1949,atthefirst-ever academic conferencededicated to anxiety, thepresident of the AmericanPsychopathologicalAssociation opened theproceedings by concedingthat although everyoneknewthatanxietywas“themost pervasivepsychologicalphenomenon

ofourtime,”nobodycouldagree on exactly what itwasorhowtomeasure it.Fifteen years later, at theannual conference of theAmerican PsychiatricAssociation, TheodoreSarbin, an eminentpsychologist, suggestedthat “anxiety” should beretired from clinical use.“The mentalistic andmulti-referenced term

‘anxiety’ has outlived itsusefulness,” he declared.(Since then,of course, theuse of the term has onlyproliferated.) Morerecently, Jerome Kagan, apsychologist at Harvardwhoisperhapstheworld’sleading expert on anxietyas a temperamental trait,has argued that applyingthe same word—“anxiety”—“to feelings

(the sensation of a racingheart or tense musclesbeforeenteringacrowdofstrangers), semanticdescriptions (a report ofworry over meetingstrangers), behaviors(tensefacialexpressionsina social situation), brainstates (activation of theamygdala to angry faces),or a chronic mood ofworry (general anxiety

disorder) is retardingprogress.”How can we make

scientific, or therapeutic,progress if we can’t agreeonwhatanxietyis?Even Sigmund Freud,

theinventor,moreor less,of the modern idea ofneurosis—amanforwhomanxiety was a key, if notthe key, foundationalconcept of his theory of

psychopathology—contradicted himselfrepeatedlyover thecourseof his career. Early on, hesaid that anxiety arosefrom sublimated sexualimpulses (repressed libido,hewrote,wastransformedinto anxiety “as wine tovinegar”).§ Later in hiscareer, he argued thatanxiety arose fromunconscious psychic

conflicts.‖ Late in his life,inThe Problem of Anxiety,Freudwrote: “It is almostdisgraceful that after somuchlaborweshouldstillfind difficulty inconceiving of the mostfundamentalmatters.”If Freud himself,

anxiety’s patron saint,couldn’t define theconcept, how am Isupposedto?

Fear sharpens thesenses. Anxietyparalyzesthem.—KURTGOLDSTEIN,TheOrganism:AHolisticApproachtoBiology

(1939)

Standard dictionarydefinitionsmake fear (“anunpleasantemotioncausedbythebeliefthatsomeone

orsomethingisdangerous,likely to cause pain, or athreat”) and anxiety (“afeeling of worry,nervousness, and unease,typicallyaboutaneventorsomething with anuncertain outcome”) seemrelativelysynonymous.Butfor Freud, whereas fear(Furcht in German) has aconcrete object—the lionthat’s chasing you, the

enemy sniper that’s gotyou pinned to yourposition in battle, or evenyour knowledge of theconsequences of missingthe crucial free throwyou’re about to shoot intheclosingmomentsofanimportantbasketballgame—anxiety(Angst)doesnot.According to this view,fear, properly occasioned,is healthy; anxiety, which

is often “irrational” or“free-floating,”isnot.a“When a mother isafraid that her child willdie when it has only apimpleoraslightcoldwespeakofanxiety;butifsheis afraid when the childhas a serious illness wecall her reaction fear,”Karen Horney wrote in1937.“Ifsomeoneisafraidwhenever he stands on a

height or when he has todiscuss a topic he knowswell, we call his reactionanxiety; if someone isafraid when he loses hisway high up in themountains during a heavythunderstorm we wouldspeak of fear.” (Horneyfurther elaborated herdistinction by saying thatwhile you always knowwhen you are afraid, you

can be anxious withoutknowingit.)InFreud’slaterwritings,he replacedhisdistinctionbetween fear and anxietywith a distinction insteadbetween “normal anxiety”(definedasanxietyaboutalegitimate threat, whichcan be productive) and“neuroticanxiety”(anxietyproduced by unresolvedsexual issues or internal

psychic conflicts, which ispathological andcounterproductive).So am I, with myphobias and worries andgeneral twitchiness,“neurotically” anxious?Orjust“normally”so?What’sthe difference between“normal” anxiety andanxiety as a clinicalproblem? Whatdifferentiates the

appropriate and evenhelpful nervousness that,say, a law student feelsbeforetakingthebarexamor that a Little Leaguerfeels before stepping intothe batters’ box from thedistressing cognitive andphysical symptoms thatattend the official anxietydisorders as defined bymodern psychiatry since1980:panicdisorder,post-

traumatic stress disorder(PTSD), specific phobia,obsessive-compulsivedisorder (OCD), socialanxiety disorder,agoraphobia, andgeneralized anxietydisorder?To distinguish the“normal” from the“clinical,” and thedifferent clinicalsyndromes from one

another, pretty mucheveryone in the entirewide-ranging field ofmental health care relieson the AmericanPsychiatric Association’sDiagnostic and StatisticalManual (now in its just-published fifth edition,DSM-V). The DSM defineshundreds of mentaldisorders, classifies thembytype,andlists,inlevels

of detail that can seemboth absurdly precise andcompletely random, thesymptoms (how many,howoften, andwithwhatseverity) a patient mustdisplay inorder toreceivea given psychiatricdiagnosis. All of whichlends the appearance ofscientific validity to thediagnosing of an anxietydisorder.But the reality is

that there is a largequotient of subjectivityhere (both on the part ofpatients, in describingtheir symptoms, and ofclinicians, in interpretingthem).StudiesoftheDSM-II found that when twopsychiatrists consulted thesame patient, they gavethe same DSM diagnosisonly between 32 and 42percent of the time. Rates

of consistency haveimproved since then, butthe diagnosis of manymental disorders remains,despite pretensions to thecontrary, more art thanscience.bConsider therelationship betweenclinical anxiety andclinical depression. Thephysiological similaritiesbetween certain forms of

clinical anxiety (especiallygeneralized anxietydisorder) and clinicaldepression are substantial:both depression andanxietyareassociatedwithelevatedlevelsofthestresshormonecortisol,andtheyshare someneuroanatomical features,including shrinkage of thehippocampus and otherparts of the brain. They

share genetic roots, mostnotably in the genesassociated with theproduction of certainneurotransmitters, such asserotonin and dopamine.(Some geneticists say theycan find no distinctionbetween major depressionand generalized anxietydisorder.) Anxiety anddepression also have asharedbasisinafeelingof

a lack of self-esteem orself-efficacy. (Feeling likeyou have no control overyour life is a commonroute to both anxiety anddepression.) Moreover,reamsofstudiesshowthatstress—ranging from jobworries to divorce tobereavement to combattrauma—is a hugecontributortoratesofbothanxiety disorders and

depression, as well as tohypertension, diabetes,and other medicalconditions.If anxiety disorders anddepression are so similar,why do we distinguishbetween them? Actually,for a few thousand years,we didn’t: doctors tendedto group anxiety anddepression together underthe umbrella terms

“melancholia” or“hysteria.”c The symptomsthatHippocratesattributedto melaina chole in thefourth century B.C.included those we wouldtoday associate with bothdepression (“sadness,”“moral dejection,” and“tendencytosuicide”)andanxiety(“prolongedfear”).In1621,inTheAnatomyofMelancholy, Robert Burton

wrote, with a clinicalaccuracy that modernresearch supports, thatanxiety was to sorrow “asister, fidusAchates [trustysquire], and continualcompanion, an assistantand a principal agent inthe procuring of thismischief; a cause andsymptomastheother.”d Itis a fact—I say this fromexperience—that being

severely anxious isdepressing. Anxiety canimpedeyour relationships,impair your performance,constrict your life, andlimityourpossibilities.The dividing linebetween the set ofdisorders the AmericanPsychiatric Associationlumps under “depression”and the set of disorders itlumps under “anxiety

disorders”—and, for thatmatter, the line betweenmental health and mentalillness—seems to be anartifactasmuchofpoliticsand culture (andmarketing) as of science.Every time the scope of agiven psychiatric disordergrows or shrinks in theDSM’s definition, it haspowerfully ramifyingeffectson everything from

insurance reimbursementstodrugcompanyprofitstothe career prospects oftherapists in differentfields and subspecialties.Quite a few psychiatristsand drug industry criticswill tell you that anxietydisorders do not exist innature but rather wereinvented by thepharmaceutical-industrialcomplexinordertoextract

money from patients andinsurance companies.Diagnoses such as socialanxietydisorderorgeneralanxiety disorder, thesecritics say, turn normalhuman emotions intopathologies, diseases forwhich medication can beprofitably dispensed.“Don’tallowthesumtotalof your life to be reducedto phrases like clinical

depression, bipolardisorder, or anxietydisorder,” says PeterBreggin,aHarvard-trainedpsychiatrist who hasbecomeafierceantagonistof the pharmaceuticalindustry.As someone who hasbeendiagnosedwithsomeof these disorders, I cantell you the distress theycause is not invented; my

anxiety, which can attimes be debilitating, isreal. But are my nervoussymptoms necessarilyconstitutiveofanillness,ofa psychiatric disorder, asthe DSM and thepharmaceutical companieswould have it? Mightn’tmy anxiety be just anormal human emotionalresponsetolife,eveniftheresponse is perhaps

somewhatmore severe forme than for others? Howdo you draw thedistinction between“normal”and“clinical”?You might expect thatrecent scientific advanceswould make thedistinction betweennormal and clinicalanxiety more precise andobjective—andcertainlyinsome ways they have.

Neuroscientists, workingwith functional magneticresonance imaging (fMRI)technology that enablesthem to observe mentalactivity in real time bymeasuring oxygenatedblood flow to differentregions of the brain, haveproduced hundreds ofstudies demonstratingassociations betweenspecific subjectively

experienced emotions andspecific kinds ofphysiological activity thatcan be seen on a brainscan. For instance, acuteanxiety generally appearson fMRI scans ashyperactivity in theamygdala, that tinyalmond-shaped structurelocateddeepinthemedialtemporal lobes near thebase of the skull.

Reductions in anxiety areassociatedwithdiminishedactivity in the amygdalaand with heightenedactivity in the frontalcortex.eAll of which makes itsound like you should beable to identify anxiety,andgaugeits intensity,onthe basis of somethingakintoanX-ray—thatyoucould differentiate

between normal andclinicalanxietyinthewayX-rays can differentiatebetween a broken ankleandasprainedone.Except you can’t. There

are people who exhibittelltale physiological signsofanxietyonabrain scan(their amygdalae light upcolorfully in response tostress-inducingstimuli)butwhowill tell you theyare

not feeling anxious.Moreover, the brain of aresearch subject who issexually aroused by apornographic movie willlightuponanMRIscaninmuchthesamewayitdoesin response to a fear-inducing event; the sameinterconnected braincomponents—theamygdala, the insularcortex, and the anterior

cingulate—will beactivated in both cases. Aresearcher looking at thetwo brain scans withoutknowing their contextmight be unable todetermine which image isa response to fear andwhichistosexualarousal.When an X-ray shows afractured femur but thepatient reports no pain,the medical diagnosis is

stillabrokenleg.WhenanfMRI exhibits intenseactivity in the amygdalaand basal ganglia and thepatient reportsnoanxiety,thediagnosisis…nothing.

When it comes todetecting andresponding to danger,the [vertebrate] brainjust hasn’t changedmuch.Insomewayswe

areemotionallizards.—JOSEPHLEDOUX,TheEmotionalBrain(1996)

Researchers sinceAristotle have madefrequent recourse to“animal models” ofemotion, and the manythousands of animalstudies conducted each

yeararepredicatedonthenotion that the behaviors,genetics, andneurocircuitryofaratorachimpanzee are similarenoughtoourownthatwecan glean relevant insightfrom them.Writing inTheExpression of the Emotionsin Man and Animals in1872, Charles Darwinobserved that fearreactions are fairly

universal across species:all mammals, includinghumans, exhibit readilyobservable fear responses.In the presence ofperceiveddanger,rats,likepeople, instinctively run,freeze, or defecate.f Whenthreatened, thecongenitally “anxious” rattrembles, avoids openspaces, prefers familiarplaces,stopsinitstracksif

encountering anythingpotentially threatening,and emits ultrasonicdistress calls. Humansdon’t issue ultrasonicdistress calls—but whenwe get nervous, we dotremble, shy away fromunfamiliar situations,withdraw from socialcontact,andprefer tostayclose to home. (Someagoraphobics never leave

their houses.) Rats thathave had their amygdalaeremoved (or whose geneshave been altered so thattheir amygdalae are notworking properly) areincapable of expressingfear; the same is true ofhumans whose amygdalaegetdamaged. (Researchersat the University of Iowahave for years beenstudyingawoman,known

in the literature as S.M.,whose amygdala wasdestroyedbyararedisease—and who cannot, as aconsequence, experiencefear.) Moreover, ifcontinuously exposed tostressful situations,animalswilldevelopsomeof the same stress-relatedmedical conditions thathumans do: high bloodpressure, heart disease,

ulcers,andsoforth.“With all or almost allanimals, evenwith birds,”Darwin wrote, “terrorcauses the body totremble.Theskinbecomespale,sweatbreaksout,andhair bristles. Thesecretions of thealimentary canal and ofthe kidneys are increased,and they are involuntarilyvoided, owing to the

relaxationof the sphinctermusclesas isknown tobethecasewithman,andasI have seen with cattle,dogs, cats, and monkeys.The breathing is hurried.The heart beats quickly,wildly, and violently.…Thementalfacultiesaremuch disturbed. Utterprostration soon follows,andevenfainting.”Darwinpointedout that

this automatic physicalresponse to threat isevolutionarily adaptive.Organisms that respond todanger in this way—bybeing physiologicallyprimed to fight or flee, ortofaint—aremorelikelytosurvive and reproducethanorganisms thatdon’t.In 1915, Walter Cannon,thechairofthephysiologydepartment at Harvard

MedicalSchool,coinedtheterm “fight or flight” todescribe Darwin’s idea ofan “alarm reaction.” AsCannon was the first todocument systematically,when the fight-or-flightresponse is activated,peripheral blood vesselsconstrict, directing bloodaway from the extremitiesto the skeletalmuscles, sothe animal will be better

prepared to fight or run.(This streaming of bloodawayfromtheskiniswhatmakesa frightenedpersonappear pale.) Breathingbecomes fasteranddeepertokeepthebloodsuppliedwith oxygen. The liversecretes an increasedamount of glucose, whichenergizes various musclesand organs. The pupils oftheeyesdilateandhearing

becomes more acute sothat the animal canbetterappraise the situation.Bloodflowsawayfromthealimentary canal anddigestive processes stop—saliva flow decreases(causing that anxiousfeeling of a dry mouth),and there isoftenanurgeto defecate, urinate, orvomit. (Expelling wastematerial allows the

animal’s internal systemsto focus on survival needsmore immediate thandigestion.) In his 1915book, Bodily Changes inPain, Hunger, Fear andRage, Cannon provided acouple of simple earlyillustrationsofthewaytheexperience of emotiontranslates concretely intochemical changes in thebody. In one experiment,

he examined the urine ofnine college students afterthey had taken a hardexam and after they hadtaken an easy one: afterthehardexam,fouroftheninestudentshadsugarintheir urine; after the easyexam, only one of themdid. In the otherexperiment, Cannonexamined the urine of theHarvard football team

after “the final and mostexciting contest” of 1913and found that twelve ofthe twenty-five sampleshad positive traces ofsugar.The physiological

response that producesfainting is different fromthe one that primes theorganism for fighting orfleeing, but it can beequally adaptive: animals

that respond to bleedinginjurieswith a sharp dropin blood pressure sufferless blood loss; also,fainting is an involuntaryway for animals to feigndeath, which in certaincircumstances might beprotective.gWhen the fight-or-flight

reaction is activatedappropriately, in responseto a legitimate physical

danger, it enhances ananimal’s chances ofsurvival.Butwhathappenswhen the response isactivated inappropriately?The result of aphysiologicalfearresponsethat has no legitimateobject, or that isdisproportionate to thesize of the threat, can bepathological anxiety—anevolutionary impulse gone

awry. William James, thepsychologist andphilosopher, surmised thatthe cause of severeanxiety, and of what wewould today call panicattacks, might bemodernity itself—specifically, the fact thatour primitive fight-or-flight responses are notsuited to moderncivilization. “The progress

from brute to man ischaracterized by nothingsomuchasbythedecreasein frequency of properoccasions for fear,” Jamesobserved in 1884. “Incivilizedlife, inparticular,it has at last becomepossible for largenumbersofpeople topass fromthecradletothegravewithouteverhavinghadapangofgenuinefear.”h

Inmodernlife,occasionsfor what James called“genuine” human fear ofthe sort occasioned in thestate of nature—beingchased by a saber-toothedtiger, say, or encounteringmembers of an enemytribe—are relatively rare,at least most of the time.Thethreatsthattodaytendto activate fight-or-flightphysiology—the

disapprovinglookfromtheboss, themysterious letteryourwifegotfromheroldboyfriend, the collegeapplication process, thecrumblingoftheeconomy,the abiding threat ofterrorism, the plummetingof your retirement fund—arenotthesortsofthreatstheresponseisdesignedtohelpwith.Yetbecausetheemergency biological

response gets triggeredanyway, especially inclinically anxious people,weendupmarinatinginastew of stress hormonesthat is damaging to ourhealth. This is becausewhether you are in thethroes of neurotic anxietyor responding to a realthreat likeamuggingorahouse fire, the autonomicactivity of your nervous

system is roughly thesame. The hypothalamus,a small part of the brainlocated just above thebrain stem, releases ahormone calledcorticotropin-releasingfactor(CRF),whichinturninduces the pituitarygland, a pea-size organprotruding from thebottom of thehypothalamus, to release

adrenocorticotropinhormone (ACTH), whichtravels through thebloodstream to thekidneys, instructing theadrenalglandssittingatopthemtoreleaseadrenaline(also known asnorepinephrine) andcortisol,whichcausemoreglucosetobereleasedintothe bloodstream, whichincreases heart and

breathing rates andproduces the state ofheightened arousal thatcanbesousefulinthecaseof actual danger and somisery inducing in thecaseofapanicattackorofchronic worrying. A largebody of evidence suggeststhathavingelevatedlevelsofcortisol foranextendedperiod of time produces ahost of deleterious health

effects, ranging from highblood pressure to acompromised immunesystem to the shrinking ofthehippocampus,apartofthe brain crucial tomemory formation. Ananxious physiologicalresponse deployed at theright time can help keepyou alive; that sameresponse deployed toooften and at the wrong

times can lead toanearlydeath.Like animals, humans

can easily be trained toexhibit conditioned fearresponses—that is, toassociate objectivelynonfrightening objects orsituations with realthreats. In 1920, thepsychologist John Watsonfamously used classicalconditioning to produce

phobic anxiety in aneleven-month-old boy hecalled Little Albert. AfterWatson repeatedly paireda loud noise—whichprovoked crying andtremblingintheboy—withthepresenceofawhiterat(the “neutral stimulus”),he was able to elicit anacute fear response in theboy simply by presentingthe rat alone, without the

noise. (Before theconditioning, Little Alberthad happily played withthe rat on his bed.) Soonthe boy had developed afull-blownphobianotonlyof rats and other smallfurry animals but also ofwhitebeards.(SantaClausterrified Little Albert.)Watson concluded thatLittle Albert’s phobiademonstratedthepowerof

classical conditioning. Forthe early behaviorists,phobic anxiety in bothanimals and humans wasreducible tostraightforward fearconditioning; clinicalanxiety,inthisview,wasalearnedresponse.iFor evolutionarybiologists, anxiety ismerely an atavistic fearresponse, a hardwired

animalinstincttriggeredatthewrong time or for thewrong reasons. Forbehaviorists, anxiety is alearned responseacquired,like Pavlov’s dogs’propensityforsalivatingatthe sound of a bell,through simpleconditioning.According toboth, anxiety is as muchananimaltraitasahumanone.“Contrarytotheview

of some humanists, Ibelieve that emotions areanything but uniquelyhuman traits,” theneuroscientist JosephLeDoux writes, “and, infact, that some emotionalsystems in the brain areessentially the samein … mammals, reptiles,and birds, and possiblyamphibians and fishes aswell.”

But is the sort ofinstinctive, mechanisticresponse that a mousedisplaysinthepresenceofacat,orwhenithearsthebell associated with ashock—or even that LittleAlbertdisplayedafterhe’dbeentrainedtofeartherat—reallyanxietyofthesortthat I feel when boardingan airplane or obsessingaboutmyfamily’sfinances

or about the mole on myforearm?Or consider this: Even

Aplysia californica, amarine snail with aprimitive brain and nospine, can demonstrate aphysiological andbehavioral response thatwould, if exhibited by ahuman, be biologicallyequivalent (more or less)to anxiety. Touch its gill

andthesnailwillrecoil,itsblood pressure will rise,and its heart rate willincrease.Isthatanxiety?Orwhataboutthis:Evenbrainless, nerveless single-celledbacteria canexhibita learned response anddisplay what psychiatristscall avoidant behavior.When the pond-dwellingparamecium encounters ashockbyanelectricbuzzer

—an aversive stimulus—itwill retreat andthenceforth seek to avoidthe buzzer by swimmingaway from it. Is thatanxiety? By somedefinitions,itis:accordingto the Diagnostic andStatistical Manual,“avoidance” of fearfulstimuli is one of thehallmarksofalmostalltheanxietydisorders.

Other experts say thatthe presumed analogiesbetween animal andhuman behavioralresponse are risiblyoverextended. “It is notobviousthatarat’sdisplayof an enhanced startlereaction … [is a] fruitfulmodel for all humananxiety states,” saysJerome Kagan. DavidBarlow of Boston

University’s Center forAnxiety and RelatedDisorders asks whether“entering a seeminglyinvoluntary state ofparalysis when underattack”—thesortofanimalbehavior that clearly doeshaveastrongevolutionaryand physiological parallelin humans—“really [has]anything in common withtheforebodingsconcerning

the welfare of our family,our occupation, or ourfinances?”“How many hippos

worry about whetherSocial Security is going tolast as long as they will,”asks Robert Sapolsky, aneuroscientist at StanfordUniversity, “or what theyaregoing to sayona firstdate?”“Aratcan’tworryabout

the stock marketcrashing,” Joseph LeDouxconcedes.“Wecan.”Can anxiety be reducedto a purely biological ormechanical process—theinstinctive behavioralresponse of the rat or themarine snail retreatingmindlessly from theelectric shock or of LittleAlbert conditioned, likePavlov’s dogs, to recoil

and tremble in thepresence of furry things?Or does anxiety require asense of time, anawareness of prospectivethreats, an anticipation offuture suffering—thedebilitating“fearsastothefuture” that brought mygreat-grandfather,andme,tothementalhospital?Is anxiety an animalinstinct, something we

sharewithratsandlizardsand amoebas? Is it alearned behavior,something acquirablethrough mechanicalconditioning?Orisit,afterall, a uniquely humanexperience, dependent onconsciousness of, amongotherthings,asenseofselfandtheideaofdeath?

The physician and the

philosopher havedifferent ways ofdefining thediseasesofthe soul. For instanceanger for thephilosopher is asentiment born of thedesire to return anoffense,whereasforthephysicianitisasurgingof blood around theheart.

—ARISTOTLE,DeAnima(FOURTHCENTURYB.C.)

One morning, aftermonths of wrestling infrustration with thesequestions, I dump myselfonmytherapist’scouchina heap of worry and self-loathing.“What’swrong?”Dr.W.

asks.“I’m supposed to be

writing a book aboutanxiety and I can’t evenwork out what the basicdefinition of anxiety is. Inall these thousands ofpages I’ve pored through,I’ve come across hundredsof definitions. Many ofthem are similar to oneanother, but many otherscontradict each other. Idon’t know which one touse.”

“Use the DSMdefinitions,”hesuggests.“But those aren’tdefinitions, just a list ofassociated symptoms,” Isay.j “And anyway, eventhat’s not straightforward,since the DSM is in theprocess of being revisedfortheDSM-V!”k“I know,” Dr. W. saysruefully. He laments thatthe mandarins of

psychiatry had recentlyconsidered droppingobsessive-compulsivedisorder (OCD) from theanxiety disorders categoryinthenewDSM,placingitinstead into a newcategory of “impulsivedisorders,” on a spectrumalongside ailments likeTourette’s syndrome. Hethinksthisiswrong.“Inallmy decades of clinical

work,” he says, “OCDpatients are alwaysanxious; theyworry abouttheirobsessions.”I mention that at a

conference I’d attended afew weeks earlier, one ofthe rationales given forwhy OCD might bereclassified as somethingother than an anxietydisorder was that itsgenetics and its

neurocircuitry seem to besubstantiallydifferentfromthat of the other anxietydisorders.“Goddamnedbiomedical

psychiatry!” he blurts. Dr.W. is ordinarily a gentle,even-keeledguy,andheisaggressivelyecumenical inhis approach topsychotherapy; he hastried,inhiswritingandinhis clinical practice, to

assimilate the best of allthe different therapeuticmodes into what he callsan “integrative approachto healing the woundedself.” (He is also, I shouldsay here, the BestTherapist Ever.) But hebelieves strongly thatoverthe last several decadesthe claims of thebiomedical modelgenerally, and of

neuroscience particularly,have become increasinglyarrogant and reductionist,pushing other avenues ofresearch inquiry to themarginsanddistorting thepractice of psychotherapy.Some of the more hard-core neuroscientists andpsychopharmacologists, hefeels,wouldboilallmentalprocesses down to theirsmallest molecular

components, without anysense of the existentialdimensions of humansufferingorofthemeaningof anxious or depressivesymptoms. At conferenceson anxiety, he laments,symposia on drugs andneurochemistry—many ofthem sponsored bypharmaceutical companies—have started to crowdouteverythingelse.

I tell Dr.W. I’m on theverge of abandoning theproject.“ItoldyouIwasafailure,”Isay.“Look,” he says. “That’s

your anxiety talking. Itmakes you excessivelyanxious about, amongother things, finding thecorrect definition ofanxiety.And itmakesyouworry relentlessly aboutoutcomes”—about

whether my definition ofanxiety will be“wrong”—“instead ofconcentratingon theworkitself. You need to focusyour attention. Stay ontask!”“But I still don’t know

what basic definition ofanxietytouse,”Isay.“Usemine,”hesays.

No one who has ever

been tormented byprolonged bouts ofanxiety doubts itspower to paralyzeaction, promote flight,evisceratepleasure,andskew thinking towardthe catastrophic. Nonewould deny howterribly painful theexperience of anxietycanbe.The experienceof chronic or intense

anxietyisaboveallelsea profound andperplexingconfrontation withpain.—BARRYE.WOLFE,UnderstandingandTreatingAnxietyDisorders(2005)

As it happens, I hadchosen Dr. W. as a

therapist a few yearsearlier precisely because Ifound his conception ofanxiety interestingandhisapproachtotreatmentlessrigid or ideological thanprevious therapists I’dworked with. (Also, Ithought the author photoon his book jacket madehimlookkindly.)I discovered Dr. W.’swork when, while in

Miami attending anacademic conference onanxiety, I stumbled acrossa book he had recentlypublished on a displaytable outside a hotelballroom. Though thebook, a guide to treatinganxiety disorders, wasgearedtowardprofessionalpsychotherapists, his“integrative”conceptionofanxiety appealed to me.

Also, after reading somanyspecializedbooksonthe neuroscience ofanxiety that featuredsentences like “Thetaactivityisarhythmicburstfiringpatternofneuronsinthe hippocampus andrelated structures which,because it is synchronousacross very large numbersofcells,oftengivesrise toa high-voltage quasi-

sinusoidal electrographicslow ‘theta rhythm’(approximately5–10Hzinthe unanesthetized rat)that canbe recorded fromthehippocampalformationunder a variety ofbehavioural conditions,” Ifound his writing to beclearandnontechnicalandhis approach to hispatients refreshinglyhumanistic. I recognized

my own issues—the panicattacks, the dependencyproblems, the sublimatedfear of death masked asanxiety aboutmore trivialthings—in many of thecasestudiesinhisbook.I had recently moved

from Boston toWashington, D.C., andfound myself for the firsttime in a quarter centurywithout a regular

psychotherapist.SowhenIread in Dr. W.’s author’snotethathehadapracticein the Washington area, Ie-mailed him to ask if hewas accepting newpatients.Dr.W.hasnotcuredmeof my anxiety. But hecontinues to insist that hewill, and in my morehopeful moments I evensort of think hemight. In

the meantime, he hasprovided me with usefultools for trying tomanageit, good and steadypractical advice, and,perhapsmost important, ausable definition—or ataxonomy of definitions—ofanxiety.AccordingtoDr.W.,thecompeting theories of andtreatment approaches toanxiety can be grouped

into four basic categories:the psychoanalytic, thebehavioral and cognitive-behavioral, thebiomedical, and theexperiential.lThe psychoanalytic

approach—crucial aspectsof which, thoughFreudianism has beenwidely repudiated inmostscientific circles, stillpermeate modern talk

therapy—holds that therepression of taboothoughts and ideas (oftenof a sexual nature) or ofinner psychic conflictsleads to anxiety.Treatment involvesbringing these repressedconflicts into consciousawareness and addressingthem throughpsychodynamicpsychotherapy and the

pursuitof“insight.”Behavioristsbelieve,like

John Watson did, thatanxiety is a conditionedfear response. Anxietydisorders arise when welearn—often throughunconscious conditioning—to fear objectivelynonthreatening things orto fear mildly threateningthings too intensely.Treatment involves

correcting faulty thinkingthrough variouscombinations of exposuretherapy (exposing yourselftothefearandacclimatingto it soyour fearresponsediminishes) and cognitiverestructuring (changingyour thinking) in order to“extinguish” phobias andto “decatastrophize” panicattacks and obsessionalworrying. Many studies

are now finding thatcognitive-behavioraltherapy, or CBT, is thesafest and most effectivetreatment for many formsof depression and anxietydisorders.The biomedicalapproach (where researchhasexplodedover the lastsixtyyears)hasfocusedonthe biologicalmechanismsof anxiety—on brain

structures like theamygdala, hippocampus,locus coeruleus, anteriorcingulate, and insula, andon neurotransmitters likeserotonin, norepinephrine,dopamine, glutamate,gamma-aminobutyric acid(GABA), and neuropeptideY (NPY)—and on thegenetics that underlie thatbiology. Treatment ofteninvolves the use of

medication.Finally, what Dr. W.calls the experientialapproach to anxietydisorders takes a moreexistential perspective,considering things likepanic attacks andobsessionalworryingtobecoping mechanismsproducedbythepsycheinresponse to threats to itsintegrity or to self-esteem.

Theexperientialapproach,like the psychoanalytic,placesgreatweightonthecontent and meaning ofanxiety—rather than onthemechanisms of anxiety,which is where thebiomedicalandbehavioralapproaches concentrate—believing these can beclues to unlocking hiddenpsychic traumas orconvictions about the

worthlessness of one’sexistence.Treatment tendsto involve guidedrelaxation to reduceanxiety symptoms andhelping the patient toburrow into the anxietiesto address the existentialissues that lie beneaththem.The conflicts between

thesedifferentperspectives—and between the

psychiatrists (MDs) andthe psychologists (PhDs),between the drugproponents and the drugcritics, between thecognitive-behaviorists andthe psychoanalysts,between Freudians andJungians, between themolecular neuroscientistsand the holistic therapists—cansometimesbebitter.The stakes are high—the

future stability of largeprofessionalinfrastructuresrides on one theory oranother predominating.And the fundamentalconflict—whether anxietyis a medical disease or aspiritual problem, aproblem of the body or aproblem of the mind—isage-old,datingbacktotheclashes betweenHippocratesandPlatoand

theirfollowers.mBut while in many

places these competingtheoretical perspectivesconflict with one another,they are not mutuallyexclusive. Often theyoverlap. Cutting-edgecognitive-behavioraltherapy borrows from thebiomedical model, usingpharmacology to enhanceexposure therapy. (Studies

showthatadrugcalledD-cycloserine, which wasoriginally developed as anantibiotic, causes newmemories to be morepowerfully consolidated inthe hippocampus and theamygdala,augmenting thepotency of exposure toextinguish phobias byintensifying the power ofthe new, nonfearfulassociations to override

the fearful ones.) Thebiomedical view, for itspart, increasinglyrecognizes the power ofthings likemeditationandtraditional talk therapy torender concrete structuralchanges in brainphysiology that are everybitas“real”asthechangeswrought by pills orelectroshock therapy. Astudy published by

researchers atMassachusetts GeneralHospital in 2011 foundthat subjects whopracticed meditation foran averageof just twenty-sevenminutesadayoveraperiod of eight weeksproduced visible changesin brain structure.Meditation led todecreased density of theamygdala, a physical

changethatwascorrelatedwithsubjects’self-reportedstress levels—as theiramygdalae got less dense,the subjects felt lessstressed. Other studieshave found that Buddhistmonks who are especiallygood at meditating showmuch greater activity intheir frontal cortices, andmuch less in theiramygdalae, than normal

people.n Meditation anddeep-breathing exercisesworkforsimilarreasonsaspsychiatric medicationsdo, exerting their effectsnot just on some abstractconcept of mind butconcretely on our bodies,on the somatic correlatesof our feelings. Recentresearch has shown thateven old-fashioned talktherapycanhavetangible,

physical effects on theshape of our brains.Perhaps Kierkegaard waswrongtosaythatthemanwho has learned to be inanxiety has learned themost important, or themost existentiallymeaningful, thing—perhaps theman has onlylearned the righttechniques for controllinghishyperactiveamygdala.o

Darwin observed thatthe equipment thatproduces panic anxiety inhumans derives from thesameevolutionaryrootsasthe fight-or-flight reactionof a rat or the aversivemaneuvering of a marinesnail. Which means thatanxiety, for all thephilosophizing andpsychologizing we’veattached to it, may be an

irreducibly biologicalphenomenonthatisnotsodifferent in humans thaninanimals.What,ifanything,dowe

lose when our anxiety isreduced to the stuff of itsphysiological components—to deficiencies inserotoninanddopamineorto an excess of activity inthe amygdala and basalganglia? The theologian

Paul Tillich, writing in1944,suggestedthatAngstwasthenaturalreactionofman to “fear of death,conscience, guilt, despair,daily life,etc.”ForTillich,thecrucialquestionof lifewas: Are we safe in somedeity’s care, or are wetrudging along pointlesslytoward death in a cold,mechanical, andindifferent universe? Is

finding serenity mainly amatterof coming to termswith that question? Or isit,rathermoremundanely,a matter of properlycalibrating levels ofserotonin in the synapses?Or are these somehow,afterall,thesamething?

Perhapsman is one ofthe most fearfulcreatures, since added

to the basic fears ofpredators and hostileconspecifics comeintellectually basedexistentialfears.—IRENÄUSEIBL-EIBESFELDT,“FEAR,

DEFENCEANDAGGRESSIONINANIMALSANDMAN:SOMEETHOLOGICAL

PERSPECTIVES”(1990)

Notlongago,Ie-mailedDr. W., who hasspecialized in treatinganxiety for forty years, toask him to boil hisdefinition of it down to asinglesentence.“Anxiety,” he wrote, “is

apprehension about futuresuffering—the fearfulanticipation of anunbearable catastropheone is hopeless to

prevent.” For Dr. W., thedefining signature ofanxiety,andwhatmakesitmore than a pure animalinstinct, is its orientationtoward the future. In this,Dr.W.’sthinkingisinlinewith that ofmany leadingtheorists of the emotions(for instance, RobertPlutchik, a physician andpsychologist who was oneof the twentieth century’s

mostinfluentialscholarsofthe emotions, definedanxiety as the“combination ofanticipation and fear”),and he points out thatDarwin, for all hisemphasis on thebehavioral similaritiesbetween animals andhumans, believed thesame. (“If we expect tosuffer, we are anxious,”

Darwin wrote in TheExpression of the EmotionsinManandAnimals.“Ifwehavenohopeofrelief,wedespair.”)Animalshavenoabstract concept of thefuture; they also have noabstract concept ofanxiety, no ability toworryabouttheirfears.Ananimal may experiencestress-induced “difficultyin breathing” or “spasms

oftheheart”(asFreudputit)—but no animal canworry about that symptomor interpret it in any way.An animal cannot be ahypochondriac.Also, an animal cannot

fear death. Rats andmarine snails are notabstractly aware of theprospectofacaraccident,or a plane crash, or aterrorist attack, ornuclear

annihilation—or of socialrejection, or diminishmentof status, or professionalhumiliation, or theinevitable loss of peoplewe love,or the finitudeofcorporeal existence. This,alongwithourcapacitytobe consciously aware ofthe sensationsof fear, andto cogitate about them,gives the humanexperience of anxiety an

existential dimension thatthe “alarm response” of amarine snail utterly lacks.ForDr.W.,thisexistentialdimensioniscrucial.Dr. W., echoing Freud,says that while fear isproducedby“real” threatsfrom the world, anxiety isproduced by threats fromwithin our selves. Anxietyis, as Dr. W. puts it, “asignal that the usual

defenses againstunbearably painful viewsof the self are failing.”Rather than confrontingthe reality that yourmarriage is failing,or thatyour career has notpanned out, or that youaredecliningintogeriatricdecrepitude, or that youare going to die—hardexistentialtruthstoreckonwith—your mind

sometimes insteadproduces distracting anddefensive anxietysymptoms, transmutingpsychic distress into panicattacks or free-floatinggeneral anxiety ordeveloping phobias ontowhich you project yourinner turmoil.Interestingly, a number ofrecent studies have foundthat at the moment an

anxious patient begins toreckon consciously with apreviously hidden psychicconflict, lifting it from themurk of the unconsciousintothelightofawareness,a slew of physiologicalmeasurements changemarkedly: blood pressureand heart rate drop, skinconductance decreases,levels of stress hormonesin the blood decline.

Chronic physicalsymptoms—backaches,stomachaches, headaches—often dissipatespontaneously asemotional troubles thathad previously been“somaticized,” orconverted into physicalsymptoms, get broughtintoconsciousawareness.pBut in believing that

anxiety disorders typically

arise from failedefforts toresolve basic existentialdilemmas,Dr.W.is,aswewill see, running againstthe grain of modernpsychopharmacology(which proffers theevidence of sixty years ofdrug studies to argue thatanxietyanddepressionarebased on “chemicalimbalances”),neuroscience(whose emergence has

demonstratednotonly thebrain activity associatedwith various emotionalstates but also, in somecases, the specificstructural abnormalitiesassociated with mentalillness), and temperamentstudies and moleculargenetics (which suggest,rather convincingly, apowerful role for heredityin the determination of

one’s baseline level ofanxiety and susceptibilitytopsychiatricillness).Dr. W. doesn’t dispute

the findings from any ofthosemodesofinquiry.Hebelievesmedicationcanbean effective treatment forthe symptoms of anxiety.But his view, based onthirty years of clinicalwork with hundreds ofanxiouspatients, is thatat

the root of almost allclinical anxiety is somekind of existential crisisabout what he calls the“ontological givens”—thatwewill growold, thatwewill die, thatwewill losepeople we love, that wewilllikelyendureidentity-shaking professionalfailures and personalhumiliations,thatwemuststruggle to find meaning

and purpose in our lives,and that we must maketrade-offs betweenpersonal freedom andemotional security andbetween our desires andthe constraints of ourrelationships and ourcommunities. In thisview,our phobias of rats orsnakes or cheeseorhoney(yes, honey; the actorRichard Burton could not

bear tobe ina roomwithhoney, even if it wassealedina jar,evenif thejarwasclosedinadrawer)are displacements of ourdeeperexistentialconcernsprojected onto outwardthings.Early in his career, Dr.W. treated a collegesophomore who hadtrained his entire life tobecome a professional

concert pianist. When thepatient’s professors toldhim that he wasn’ttalented enough to realizehisdream,hewasbesetbyterrible panic attacks. InDr. W.’s view, the panicwas a symptom producedbythepatient’sinabilitytoreckonwiththeunderlyingexistential loss here: theend of his professionalaspirations, the demise of

his self-conception as aconcert pianist. Treatingthe panic allowed thestudent to experience hisdespair at this loss—andthen begin to construct anew identity. Anotherpatient, a forty-three-year-old physician with athriving medical practice,developed panic disorderwhen, right around thetimehisoldersonwentoff

to college, he begangetting injuries playingtennis,asportatwhichhehadformerlyexcelled.Thepanic, Dr. W. concluded,was precipitated by thesedual losses (of his son’schildhood, of his ownathletic vigor), which incombination arousedexistential concerns aboutdecline into decrepitudeand death. By helping the

physician come to termswith these losses, and toaccept the “ontological”reality of his eventualdecline and mortality, Dr.W. enabled him to shakefree of the anxiety anddepression.qInDr.W.’sview,anxiety

andpanic symptoms serveas what he calls a“protective screen” (whatFreud called a “neurotic

defense”) against thesearing pain associatedwith confronting loss ormortality or threats toone’s self-esteem (roughlywhat Freud called theego). In some cases, theintense anxiety or panicsymptoms patientsexperience are neuroticdistractionsfrom,orawayof coping with, negativeself-images or feelings of

inadequacy—what Dr. W.calls“self-wounds.”I find Dr. W.’s

existential-meaning-basedinterpretations of anxietysymptoms to be in somewaysmoreinterestingthanthe prevailing biomedicalones.Butforalongtime,Ifoundthemodernresearchliterature on anxiety—which has much more todo with “neuronal firing

rates in the amygdala andlocus coeruleus” (as theneuroscientists put it) andwith “boosting theserotonergic system” and“inhibiting the glutamatesystem” (as thepsychopharmacologistsputit)andwithidentifyingthespecific “single-nucleotidepolymorphisms” onvarious genes that predictan anxious temperament

(as the behavioralgeneticists put it) thanwith existential issues—tobe more scientific, andmore convincing, thanDr.W.’s theory of anxiety. Istill do. But less so than Ididbefore.Notlongagoinmyown

therapy with Dr. W., wemoved gingerly into“imaginal” exposure formyphobias.rDr.W. and I

established a hierarchy offrightening situations andthen did a gentle “stageddeconditioning,” in whichI was supposed to picturecertain distressing imageswhile doing deep-breathing relaxationexercises,hopingtoreducethe anxiety these imagesstimulated. Once I’dconjured an image andwastryingtoholditinmy

mind without panicking,Dr.W.wouldaskmewhatIwasfeeling.This proved to be

surprisingly hard.Although I was sittingsafely in the consultingroomofDr.W.’ssuburbanhomeandwasfreetostopthe exercise at any time,merely imaginingfrightening scenariosbecame an agony of

anxiety.Thesmallest,mostunlikely-seeming cues—seeing myself riding on achairlift or a turbulence-racked airplane; picturingthe green bucket thatwould be placed by mybed when I had an upsetstomachasayoungboy—set me to sweating andhyperventilating. Sointense was my anxiousresponse to these purely

mentalimagesthatseveraltimes I had to leave Dr.W.’soffice towalkaroundin his backyard and calmdown.In these deconditioningsessions, Dr. W. has triedto get me to focus onwhat, precisely, I’manxiousabout.I have a hard timeanswering this question.During the imaginal

exposure—let alone whenI’m actually confrontedwitha“phobicstimulus”—I cannot focus at all onanswering the question. Ijust feel complete, all-consumingdread,andallIwant is to escape—fromterror,fromconsciousness,from my body, from mylife.sOver the course of

severalsessions,something

unexpected happened.When I tried to engagewith the phobia, I’d getderailedbysadness. I’dsiton the couch in Dr. W.’soffice, doing deepbreathing and trying topicture the scene frommy“deconditioninghierarchy,” and my mindwouldstarttowander.“Tell me what you’re

feeling,”Dr.W.wouldsay.

“A little sad,” I wouldsay.“Go with that,” he

wouldsay.And then seconds later

I’dberackedbysobs.I am embarrassed to

recount this little tale.Forone thing, how unmanlycanIbe?Foranother,Iamnot a believer in themagical emotionalbreakthrough or the

cathartic release. But IconfessthatIdidfeelsomekindofreliefasIsatthereshudderingwithsobs.This outburst of sadness

occurred each time wetriedtheexercise.“What’s going on?” I

asked Dr. W. “What doesthismean?”“It means we’re onto

something,” he said,handingmeatissuetodry

mytears.Yes, I know, everything

aboutthisscenemakesmecringe, too. But at thetime,as I sobbed thereonthe couch, Dr. W.’sstatement felt like awonderfully supportiveand authentic gesture—which touched me andmademecryevenharder.“You’re in the heart of

thewoundnow,”hesaid.

Dr.W.believes,asFreuddid, that anxiety could bean adaptation meant toshield the psyche fromsome other source ofsadnessorpain. I askhimwhy,ifthat’sthecase,theanxiety often feels muchmore intense than thesadness. As hard as it’smaking me cry, this“wound” that I’msupposedly in feels less

unpleasant than the terrorI feel when I’m on aturbulent flight, or whenI’m feeling nauseated, orwhen I was enduringseparation anxiety as achild.“That’s often the case,”

Dr.W.says.I’m not sure what to

makeofthis.WhydoIfeelso much better—happierand relatively less anxious

—after swimming aroundinmyputative“wound”?t“We don’t know yet,”

Dr. W. says. “But we’regettingsomewhere.”

* The anxiety disorders havepersisted throughthepublicationof the DSM-III-R (in 1987), theDSM-IV(in1994),theDSM-IV-TR(in 2000), and the DSM-V (in2013).

† There are long-running debatesamong psychologists andphilologists about thedifferencesbetween,say,angoisseandanxiété(not to mention inquiétude, peur,terreur, and effroi) in French andbetween Angst and Furcht (andAngstpsychosen and Ängstlichkeit)inGerman.

‡Kierkegaard, the son of aDanishwool merchant, was the firstnonphysician to write a seriousbook-lengthtreatmentofanxiety.

Some fifty years before Freud,Kierkegaarddistinguishedanxietyfromfear,defining the formerasa vague, diffuse uneasinessproducedbynoconcreteor“real”danger. Kierkegaard’s father hadrenounced God (cursed him, infact), and so young Søren wasmuch preoccupied with whetherto believe in or to reject Christ;the freedom to choose betweenthese two options—and theinability to know for certain

which one was correct—waswhat Kierkegaard believed to bethe principal wellspring ofanxiety. In this, Kierkegaardwasarguing in the vein of BlaisePascal, his seventeenth-centuryphilosophical predecessor andfellow anxiety sufferer.Kierkegaard was also givingbirth, more or less, toexistentialism; twentieth-centurysuccessors like the psychiatristKarlJaspersandthephilosopher-

novelist Jean-Paul Sartre, amongothers, would take up similarquestions about choice, suicide,engagement,andanxiety.

WhenmanlosthisfaithinGodand in reason, existentialists likeKierkegaard and Sartre believed,he found himself adrift in theuniverse and therefore adrift inanxiety.Butfortheexistentialists,what generated anxiety was notthegodlessnessof theworld,perse, but rather the freedom to

choose between God andgodlessness. Though freedom issomething we actively seek, thefreedom to choose generatesanxiety. “When I behold mypossibilities,” Kierkegaard wrote,“Iexperiencethatdreadwhichisthedizzinessoffreedom,andmychoice is made in fear andtrembling.”

Manypeopletrytofleeanxietyby fleeing choice. This helpsexplain the perverse-seeming

appeal of authoritarian societies—the certainties of a rigid,choiceless society can be veryreassuring—and why times ofupheaval so often produceextremistleadersandmovements:Hitler in Weimar Germany,Father Coughlin in Depression-era America, or Jean-Marie LePeninFranceandVladimirPutininRussiatoday.Butrunningfromanxiety, Kierkegaard believed,was a mistake because anxiety

wasa“school”thattaughtpeopletocometotermswiththehumancondition.

§ Someof Freud’s firstwritings onthe subject boil anxiety down topure biomechanics: neuroticanxiety,hetheorized,wasmainlythe result of repressed sexualenergy. Trained as a neurologist(his early research was on thenervous system of eels), Freudsubscribed to the principle ofconstancy, which held that the

human nervous system tends totry to reduce, or at least holdconstant, the quantity of“excitation” it contains. Sexualactivity—orgasm—was aprincipal means by which thebodydischargedexcesstension.

Such beliefs about the relationbetween sexual tension andanxiety had ancient precedent.The Roman physician Galendescribes treating a patient,whose brain he believed was

affected by the rotting of herunreleased sexual fluids, “with amanualstimulationofthevaginaand of the clitoris.” The patient“took great pleasure from this,”Galen reports, “and much liquidcameout,andshewascured.”

‖ His acolytes and would-besuccessors then spent ageneration arguing over whatthose conflicts might be about:Karen Horney said “dependencyneeds,” Erich Fromm said

“security needs,” and AlfredAdlersaid“theneedforpower.”

aThisFreudianviewofAngsthasaKierkegaardian “quality ofindefinitenessandlackofobject.”

bThebitterfightsoverrevisionsfortheDSM-V—whichhaveincludedpublic denunciations of it by thechairmen of the task forces thatproduced the DSM-III and DSM-IV, respectively—suggest thatpsychiatric diagnosis may bemore a matter of politics and

marketing than either art orscience.

c Some historians of science lumpall the syndromes with this“matrix of distress symptoms”—psychological symptoms likeworry and sadness and malaise,as well as physical ones likeheadaches, fatigue, back pain,sleeplessness, and stomachtrouble—under the broadcategoryofthe“stress tradition.”“Stress” can refer to both

psychological stresses andphysical ones, in the formof the“stress” placed on the biologicalnervoussystemthatdoctorssincethe eighteenth century believedcaused“nervousdisease.”

dBurtonwrotethat inthedaytimemelancholics “are affrighted stillby some terribleobject,and tornin pieces with suspicion, fear,sorrow, discontents, cares,shames,anguish,etc.,assomanywild horses, that they cannot be

quiet an hour, a minute of thetime.”

e I’m oversimplifying—the fullneuroscientific picture is morecomplexanddetailed—butthisisthe gist of what research hasfound. During intensely anxiousmoments, the primitive effusionsof the amygdala overpower themore rational thinking of thecortex.

f Defecation rate—the number ofpellets dropped perminute—is a

standard measure of fearfulnessinrodents.Inthe1960s,scientistsat a psychiatric hospital inLondon bred the famousMaudsley strain of reactive ratsby pairing animals with similarpoopfrequencies.

g Here’s another way in whichwriting this book has been badfor me: before I startedresearching it, I wasn’t familiarwith blood-injury phobia—acondition that causes the

estimated4.5percentofpeopleitafflicts to get extremely anxiousandsometimes,becauseofadropin blood pressure, to faint wheninjected with needles or at thesightofblood—andwasthereforeable to get shots and have myblood drawn without distress, arare area of relativenoncowardice for me. Now,having learned about thephysiology that produces thisphenomenon, I have become

phobic about fainting in thesesituationsandhave,bythepowerofautosuggestion,nearlydonesoseveraltimes.

“ForGod’ssake,Scott,”Dr.W.says when I tell him about this.“You’ve given yourself a newphobia.” (He advises that Ipractice getting injected by aphysician soon—a form ofexposure therapy—before thephobia becomes a seriousproblem.)

h William (along with his brotherHenryandsisterAliceandseveralother siblings) seems to haveinherited his own anxious,hypochondriacal tendencies fromhis father, Henry James Sr., aneccentric Swedenborgianphilosopher who, in an 1884letter to William, provided adescription of an experienceeasilyrecognizabletothemodernclinician as a panic attack: “Oneday… toward the close ofMay,

having eaten a comfortabledinner, I remained sitting at thetable after the family haddispersed, idly gazing at theembers in the grate, thinking ofnothing…when suddenly—in alightning-flash as it were—‘fearcame upon me, and trembling,which made all my bones toshake’ [he’s quoting Job here].… The thing had not lasted tenseconds before I felt myself awreck; that is, reduced from a

state of firm, vigorous, joyfulmanhood to one of almosthelplessinfancy.”

iThepurebehavioristviewof fearconditioning is complicated, ifnot largely undermined, by thefact that humans and othermammals seem geneticallyhardwired to develop phobias ofcertain things but not others.Today,evolutionarypsychologistssay Watson misinterpreted hisLittleAlbert experiment: the real

reason Albert developed such aprofound phobia of rats was notbecause behavioral conditioningis so intrinsically potent butbecause the human brain has anatural—and evolutionarilyadaptive—predisposition to fearsmallfurrythingsonthebasisofthediseasestheycarry.(Iexplorethis at greater length in chapter9.)

jForexample,here’showtheDSM-IV defines generalized anxiety

disorder: “Excessive anxietyabout a number of events oractivities, occurring more daysthan not, for at least 6 months.The person finds it difficult tocontrol the worry. The anxietyandworryareassociatedwithatleast three of the following sixsymptoms (with at least somesymptoms present formore daysthannot, for thepast6months):Restlessness or feeling keyed uporonedge;Beingeasilyfatigued;

Difficulty concentrating or mindgoing blank; Irritability; Muscletension; Sleep disturbance.” (TheDSM-IVdoesinoneplaceprovidea general definition of anxietythat I think is, although bothgeneric and technical, fairlyaccurate: “The apprehensiveanticipation of future danger ofmisfortune accompanied by afeeling of dysphoria or somaticfeelings of tension. The focus ofanticipated danger may be

internalorexternal.”)

k I had this conversationwith himbefore the new DSM-V waspublishedin2013.

l This schematic overview of thedifferent theoretical approachesto anxiety is necessarilysomewhatoversimplified.

m Modern science has eventuallyshown Hippocrates to be themore correct—the mind doesarisefromthephysicalbrainand,

infact,fromthewholebody—butPlato’s influence on the study ofpsychology has neverthelessremainedpowerfulandenduring,in part because of his influenceon Freud. In the Phaedrus, Platodescribes the soul as a team oftwohorses anda charioteer: onehorse is powerful but obedient,the other is violent and illbehaved,andthecharioteermustwrestle mightily to make themwork together to move ahead.

Thisviewofthehumanpsycheasdivided into three parts—thespiritual, the libidinal, and therational—presages the Freudianmind, with its id, ego, andsuperego. For Plato, even morethan for Freud, successfulpsychological adjustmentdepended on the rational soul(logistikon) keeping the libidinalsoul (epithumetikon) in check.ThispassagefromPlato’sRepublicuncannily prefigures Freud’s

Oedipuscomplex:“Allourdesiresarearousedwhen…therationalpartsofoursoul,allourcivilizedand controlling thoughts, areasleep. Then the wild animal inus rises up, perhaps encouragedbyalcohol,andpushesawayourrational thoughts: in such states,menwilldoanything,willdreamof sleeping with their mothersand murdering people.” (WhenWilfred Trotter, an influentialBritishneurosurgeonof theearly

twentieth century, came acrossthis passage, he declared, “Thisremark of Plato makes Freudrespectable.”)

n The very best meditators seemeven tobeable to suppress theirstartle response, a rudimentaryphysiological reaction to loudnoises or other sudden stimulithat is mediated through theamygdala. (The strength of one’sstartle response—whethermeasuredininfancyoradulthood

—has been shown to be highlycorrelatedwith thepropensity todevelop anxiety disorders anddepression.)

o For his part,William James, likeDarwin, believed that purelyphysical, instinctive processesprecededawarenessofanemotion—and, in fact, preceded theexistence of a given brain state.In the1890s,heandCarlLange,aDanishphysician,proposedthatemotions were produced by

automatic physical reactions inthe body, rather than the otherway around. According to whatbecame known as the James-Lange theory, visceral changesgenerated by the autonomicnervous system, operatingbeneaththelevelofourconsciousawareness,leadtosucheffectsaschangesinheartrate,respiration,adrenalinesecretion,anddilationof the blood vessels to theskeletal muscles. Those purely

physical effects occur first—andthen it is only our subsequentinterpretationof thoseeffects thatproduces emotions like joy oranxiety. A fearful or angeringsituation produces a series ofphysiological reactions in thebody—and then it is only theconsciousmind’sbecomingawareofthosereactions,andappraisingand interpreting them, thatproduces anxiety or anger.According to James-Lange, no

purely cognitiveorpsychologicalexperience of anything likeanxietycanbedivorcedfromtheautonomicchangesintheviscera.The physical changes come first,thentheemotion.

This suggests that anxiety isprimarilyaphysicalphenomenonand only secondarily apsychological one. “My theory,”James wrote, “is that the bodilychanges follow directly theperception of the exciting fact,

and that our feeling of the samechanges as they occur is theemotion.Commonsensesays,welose our fortune, are sorry andweep; we meet a bear, arefrightened and run; we areinsultedbyarival,areangryandstrike.Thehypothesishere tobedefended says that this order ofsequence is incorrect…andthatthe more rational statement isthatwefeelsorrybecausewecry,angry because we strike, afraid

because we tremble.” Physicalstatescreatepsychiconesandnotvice-versa.

The James-Lange theory waslater undermined by research onpatientswith spinal cord injuriesthat prevented them fromreceiving any somaticinformation from their viscera—people who literally could notfeel muscle tension or stomachdiscomfort; people who were, ineffect,brainswithoutbodies—yet

who still reported experiencingthe unpleasant psychologicalsensations of dread or anxiety.This suggested that the James-Lange theory was, if not whollywrong, at least incomplete. Ifpatients unable to receiveinformation about the state oftheir bodies can still experienceanxiety, then maybe anxiety isprimarilyamentalstate,onethatdoesn’t require input from therestofthebody.

But various studies conductedsincetheearly1960ssuggestthatthe James-Lange theorywas not,afterall,completelywrong.Whenresearchers at Columbia gavestudy subjects an injection ofadrenaline, the heart rate andbreathing rate of all the subjectsincreased, and they allexperienced an intensification ofemotion—but the researcherscould manipulate what emotionthe subjects felt by changing the

context. Those subjects givenreason to feel positive emotionsfelt happy, while those givenreason to feel negative emotionsfelt angry or anxious—and ineverycasetheyfelttherespectiveemotion(whateverithappenedtobe) more powerfully than thosesubjects who had been given aplacebo injection. The injectionof adrenaline increased theintensityofemotion,butitdidnotdetermine what emotion that

would be; the experimentalcontext supplied that. Thissuggests that the autonomicsystems of the body supply themechanics of the emotion—butthe mind’s interpretation of theoutside environment supplies thevalence.

Other recent research suggeststhatJamesandLangewere rightin observing that physiologicalprocesses in thebodyare crucialto driving emotions and

determining their intensity. Forinstance, a growing number ofstudies show that facialexpressions can produce—ratherthan just reflect—the emotionsassociated with them. Smile andyou will be happy; tremble, asJames said, and you will beafraid.

pEvenasmuchofFreudianismhasbeen substantially discredited,elementsofFreud’stheorieshavegained empirical support in the

recent findings of research likethis.

q I should say here that I am notbetraying any confidentiality inwriting about these patients; Dr.W. has published (anonymous)case histories of them in variousplaces.

rThistherapydrawsonatechniquecalled systematic desensitization,which was pioneered in the1960s by Joseph Wolpe, aninfluential behavioral

psychologist, whose initialresearchwasonhowtoeliminatefearresponsesincats.

sIoncesuggestedtoDr.W.thatifIhad a gun and knew that I atleast had the option of escapingphobic terror, then maybe myanxiety would subside, sincehavingtheoptionofescapewouldgive me the feeling of somecontrol.

“Perhaps,”heconceded.“Butitwould also increase the chances

ofyouoffingyourself.”

t In their early work developingpsychoanalytic techniquestogether during the 1890s,Sigmund Freud and his mentorJosef Breuer called this catharticdredging up of suppressedthoughts and emotions “chimneysweeping.”

PARTII

AHistoryofMyNervousStomach

CHAPTER3

ARumblingintheBelly

Anxiousness—adifficult disease. Thepatient thinks he has

something likea thorn,somethingprickinghimin his viscera, andnauseatormentshim.—HIPPOCRATES,OnDiseases(FOURTHCENTURYB.C.)

I have this recurringnightmare of being illasabride,runningoutof the church and

abandoning myhusbandatthealtar.—EMMAPELLING,

QUOTEDINTHEJUNE5,2008,UNITEDPRESS

INTERNATIONALARTICLE

“BRIDE’SVOMITFEARDELAYSWEDDING”

I struggle withemetophobia, a

pathological fear ofvomiting, but it’s been alittle while since I lastvomited.Morethanalittlewhile, actually: as I typethis, it’s been, to beprecise, thirty-five years,two months, four days,twenty-two hours, andforty-nine minutes.Meaning that more than83 percent ofmy days onearth have transpired in

the timesince I last threwup, during the earlyevening of March 17,1977.Ididn’tvomitinthe1980s. I didn’t vomit inthe 1990s. I haven’tvomited in the newmillennium. And needlessto say, I hope to make itthroughthebalanceofmylife without having thatstreak disrupted.(Naturally, Iwas reluctant

even to type thisparagraph, andparticularly that lastsentence, for fear ofjinxing myself or invitingcosmic rebuke, and I amknocking wood andoffering up prayers tovariousgodsandFatesasIwritethis.)WhatthismeansisthatI

have spent, by roughcalculation, at least 60

percent ofmywaking lifethinking about andworrying about somethingthatIhavespent0percentof the last three-plusdecades doing. This isirrational.A part of me protestsinstantly:But wait, what ifit’s not irrational? What if,in fact, there’s a causalrelationship between myworrying about vomiting

andmy not doing it?Whatif my eternal vigilance iswhat protects me—throughmagic or through neuroticenhancementofmy immunesystem or through sheerobsessive germ avoidance—from food poisoning andstomachviruses?When I’ve made this

argument to variouspsychotherapists over theyears, they respond: “Let’s

say you’re right about thecausal relation—yourbehavior is still irrational.Look howmuch time youwaste, and what you’vedone to your quality oflife, worrying aboutsomething that, whileunpleasant, is generallyrare and almost alwaysmedically insignificant.”Evenifthecostofrelaxingmy vigilance was a

stomach virus or bout offood poisoning every sooften, the therapists say,wouldn’t that beworthwhile for what I’dgainingettingsomuchofmylifeback?I suppose a rational,

nonphobic person wouldanswer yes. And they’dsurelyberight.Butformethe answer remains,emphatically,no.

An astonishing portionof my life is built aroundtrying to evade vomitingand preparing for theeventuality that I might.Some of my behavior isstandard germophobicstuff: avoiding hospitalsand public restrooms,giving wide berth to sickpeople, obsessivelywashingmyhands,payingcareful attention to the

provenanceofeverythingIeat.But other behavior is

more extreme, given thestatistical unlikelihood ofmy vomiting at any givenmoment. I stash motionsickness bags, purloinedfromairplanes,allovermyhomeandofficeandcarincase I’m suddenlyovertaken by the need tovomit. I carry Pepto-

Bismol and Dramamineand other antiemeticmedicationswithmeatalltimes. Like a generalmonitoring the enemy’sadvance, I keep adetailedmental map of recordedincidences of norovirus(the most common strainof stomach virus) andother forms ofgastroenteritis, using theInternettotrackoutbreaks

in the United States andaround theworld. Such isthenatureofmyobsessionthat I can tell you at anygiven moment exactlywhich nursing homes inNew Zealand, cruise shipsin theMediterranean, andelementary schools inVirginia are contendingwith outbreaks. Once,when I was lamenting tomy father that there is no

central clearinghouse forinformation aboutnorovirus outbreaks thewaythere is for influenza,my wife interjected. “Yes,there is,” she said. Welooked at her quizzically.“You,” she said, and shehadapoint.Emetophobia has

governed my life, with afluctuating intensity oftyranny, for some thirty-

five years. Nothing—notthe thousands ofpsychotherapyappointments I’ve satthrough,notthedozensofmedicationsI’vetaken,notthe hypnosis I underwentwhen I was eighteen, notthe stomach viruses I’vecontracted and withstoodwithout vomiting—hassucceeded in stamping itout.

For several years, Iworked with a therapistnamed Dr. M., a youngpsychologist who had apractice at BostonUniversity’s Center forAnxiety and RelatedDisorders. I had originallysought treatment for mypublic speaking anxiety,butafterseveralmonthsofconsultations Dr. M.proposed that we also try

applying the principles ofwhat’s known as exposuretherapy towardextinguishing myemetophobia.Which ishow I came to

findmyselfnotlongagoatthe center of an absurdisttableau.I’m giving a speech

about the founding of thePeace Corps—which feelsa little artificial and

awkward to begin with,because the venue is asmall conference room offahallwayintheCenterforAnxiety and RelatedDisorders. My audienceconsists of Dr. M. andthree graduate studentsshe’s corralled at amoment’s notice fromaround the building.Meanwhile, in the cornerof the room, a large

television is showing avideo loop of a series ofpeoplethrowingup.“Originally, PresidentKennedy’s plan was tohouse the Peace Corpsinside the Agency forInternationalDevelopment,” I’m sayingas amanon the screen tomy right retches loudly.“But Lyndon Johnson hadbeen convinced by

Kennedy’s brother-in-lawSargent Shriver thatstuffing the Peace Corpsinside an existinggovernment bureaucracywould stifle itseffectiveness and end upneutering it.” On thescreen,vomitspattersontothefloor.Adeviceattachedtomyfinger is monitoring myheart rate and levels of

blood oxygen. Every fewminutes, Dr. M. interruptsmy speech to say: “Giveme your anxiety ratingnow.” I’m to respond bygiving her an assessmentof my anxiety at thatmomentonascaleof1to10, with 1 beingcompletely calm and 10being unalloyed terror.“About a six,” I saytruthfully. I’mlessanxious

than embarrassed andgrossedout.“Goon,”shesays,andI

resume my lecture as thecacophony of pukingcontinues on the screen.When I glance up, I cansee that the graduatestudents, two youngwomen and a youngman,aretryingtopayattentionto what I’m saying, butthey’re clearly distracted

by all the literal upheavalin the background. Themale student is lookinggreen;hisAdam’s apple istwitching. I can tell he’sfightinghisgagreflex.I’m feeling a littleanxious, yes, but alsofrankly ridiculous. How isgiving a fake speech to afake audience amidcascading images ofvomitinggoingtocureme

of my phobia of publicspeaking or of throwingup?As bizarre as this scenewas, the therapeuticprinciplesunderlyingitarewell established. Exposuretherapy—in essence,exposure to whatever’scausing the pathologicalfear,whetherthat’sratsorsnakes or airplanes orheights or throwing up—

has for dozens of yearsbeen a standard treatmentfor phobias, and it is nowan important componentof cognitive-behavioraltherapy. The logic of thisapproach—which haslatelybeenundergirdedbyneuroscience research—isthat extended exposure tothe object of fear, underthe guidance of atherapist, makes that

object less frightening.Someone with fear ofheights would,accompanied by atherapist,walkfartherandfarther out onto thebalconies of higher andhigherbuildings.Someonewith siderodromophobia(train phobia) would takea short subway ride, andthen a longer one, andthen a still-longer one,

until the fear diminishedand was graduallyextinguishedcompletely.Amore aggressive form ofexposure, known asflooding, calls for a moreintense experience. Totreat, say, airplane phobiausing the standardexposure technique, afearful flier might bestarted off with visits tothe airport to watch

airplanestakeoffandlanduntil his anxiety levelcomes down. He wouldprogress to actuallywalking onto an airplaneand getting acclimated tobeing on it, allowing theintensity of physicalresponses and fearfulemotions to crest and fall,andthenadvancetotakinga short commercial flightin the company of a

therapist. Ultimately, hewould graduate to takinglonger flights alone.Applying flooding toaerophobia might entail,instead, starting thepatientoutonatinytwin-engine plane, flying himup into the sky, andsubjectinghimtostomach-churning aeronauticalgymnastics. According tothe theory, the patient’s

anxiety will spike initiallybutwillthensubsideashelearns quickly that he cansurviveboththeflyingandthe experience of his ownanxiety. Some therapistsmaintain relationshipswith local pilots so theycan offer this sort oftherapy. (Dr.M. offered ittome;Ideclined.)David Barlow, theformer head of theCenter

for Anxiety and RelatedDisorders, says thegoalofexposure therapy is to“scare the hell out of thepatient” in order to teachhimthathecanhandlethefear. Barlow’s exposuretechniques may soundcruel and unusual, but heclaims a phobia cure rateofup to85percent (oftenwithinaweekorless),andan ample number of

studiessupportthisclaim.*TheideabehindDr.M.’s

notion of trying tocombine my exposures topublic speaking and tovomitingwastoratchetupmy anxiety as high aspossible—the better to“expose” me to it, and tothethingsthatIfeared,sothat I could begin theprocess of “extinguishing”those fears. The problem

was that these simulationswere too artificial togeneratetherequisitelevelofanxietyinme.SpeakingtoafewgraduatestudentsinDr.M.’sofficemademenervous anduncomfortable, but itnever generated anythinglike the all-consumingdread that a real publicspeakingengagementdoes—especially since I knew

that the graduate studentswere all studying anxietydisorders. I didn’t feelcompelled,asIusuallydo,totrytohidemyanxiety;Ialready assumed Dr. M.’scolleagues saw me asdamaged, and therefore Ididn’t have to go to suchanxiety-producing lengthsto hide my damagedness.So although even smallmeetings at work could

still throw me into anagony of panic—to saynothing of the large-scalepublic speakingengagements that I woulddread for months inadvance—the fauxpresentations I’d make inmy weekly sessions withDr. M. felt like clammyfacsimilesoftherealthing.Awkward and unpleasant,yes, but not sufficiently

anxiety provoking to beeffectiveexposuretherapy.Similarly, while theexperienceofwatchingthevomit videos wasdiscomfiting andunpleasant, it producednothing close to the levelof limb-trembling, soul-shakinghorrorthatfeelingabout to vomit does; Iknew the videos couldn’tinfect me, and I knew I

could always simply lookaway, or turn them off, ifmy anxiety became toomuch to bear. Crucially—and fatally, as far aseffective exposure therapywent—escape was alwayspossible.†Determining—as anumberofothertherapists,beforeandsince,alsohave—thatmyfearofvomitinglayatthecoreofmyother

fears (for instance, I’mafraid of airplanes partlybecause I might getairsick), Dr. M. proposedthat we concentrate onthat.“Makes sense to me,” Iconcurred.“There’sonlyonewaytodothatproperly,”shesaid.“Youneed to confront thephobia head-on, to exposeyourselftothatwhichyou

fearthemost.”Uh-oh.“We have to make youthrowup.”No. No way. Absolutelynot.She explained that acolleague had justsuccessfully treated anemetophobe by giving heripecac syrup, whichinduces vomiting. Thepatient,afemaleexecutive

who had flown in fromNew York to be treated,had spent a week visitingtheCenterforAnxietyandRelated Disorders. Eachday she’d take ipecacadministered by a nurse,vomit, and then processthe experience with thetherapist—“decatastrophizing” it,asthecognitive-behavioraltherapists say. After a

week, she flew back toNew York—cured, Dr. M.reported,ofherphobia.Iremainedskeptical.Dr.M. gave me an academicjournalarticlereportingona clinical case ofemetophobia successfullytreated with the ipecacexposuremethod.“This is just a singlecase,” I said. “It’s from1979.”

“Therehavebeenlotsofothers,” she said, andremindedme again of hercolleague’spatient.“Ican’tdoit.”“You don’t have to do

anythingyoudon’twanttodo,”Dr.M.said.“I’llneverforce you to do anything.But the only way toovercomethisphobiaistoconfront it. And the onlyway to confront it is to

throwup.”We had many versionsof this conversation overthe course of severalmonths. I trusted Dr. M.despite the inane-seemingexposures she cooked upforme.(Shewaskindandpretty and smart.) So oneautumndayIsurprisedherby saying I was open tothinking about the idea.Gently, reassuringly, she

talkedmethroughhowtheprocess would work. Sheand the staff nurse wouldreserve a lab upstairs formy privacy and would bewith me the whole time.I’deatsomething,taketheipecac,andvomit in shortorder(andIwouldsurvivejust fine, she said). Thenwe would work on“reframingmy cognitions”about throwing up. I’d

learn that it wasn’tsomething to be terrifiedof,andI’dbeliberated.She tookme upstairs to

meet the nurse. Nurse R.showed me the lab andtoldme that taking ipecacwas a standard form ofexposure therapy; shesaidshe’dhelpedpresideoveranumber of exposures forerstwhile emetophobes.“Just the other week, we

had a guy in here,” shesaid. “He was verynervous,butitworkedoutjustfine.”We went backdownstairs to Dr. M.’soffice.“Okay,”Isaid.“I’lldoit.Maybe.”Over the next fewweeks, we’d keepscheduling the exposure—and then I’d show up on

the appointed day anddemur, saying I couldn’tgo through with it. I didthis enough times that Ishocked Dr. M. when, onan unseasonably warmThursday in earlyDecember, I presentedmyselfatherofficeformyregular appointment andsaid,“Okay.I’mready.”The exercise was star-crossed from the

beginning. Nurse R. wasoutofipecac,soshehadtoruntothepharmacytogetsomemorewhile Iwaitedfor an hour in Dr. M.’soffice. Then it turned outthat the upstairs lab wasbooked, so the exposurewould have to take placeina smallpublic restroomin the basement. I wasconstantly on the vergeofbacking out; probably the

only reason I didn’t wasthatIknewIcould.What follows is aneditedexcerptdrawnfromthe dispassionate-as-possible account I wroteup afterward on Dr. M.’srecommendation. (Writingan emotionally neutralaccount is a commonlyprescribedwayoftryingtoforestall post-traumaticstress disorder after a

traumatic experience.) Ifyou’re emetophobicyourself, or even just alittlesqueamish,youmightwanttoskipoverit.

We met up withNurse R. in thebasement restroom.Aftersomediscussion,Itooktheipecac.Having passed thepoint of no return, I

felt my anxiety surgeconsiderably. I begantoshakealittle.Still,I was hopeful thatsickness would strikequickly and be overfast and that Iwoulddiscover theexperiencewasnotasbadasI’dfeared.Dr.M.hadattached

a pulse and oxygen-level monitor to my

finger. As we waitedfor the nausea to hit,sheaskedmetostatemyanxietylevelonascale of 1 to 10.“Aboutanine,”Isaid.By now I wasstartingtofeelalittlenauseated.SuddenlyIwasstruckbyheavingand I turned to thetoilet. I retched twice—butnothingfeltlike

it was coming up. Ikneltonthefloorandwaited, still hopingtheeventwouldcomequickly and then beover with. Themonitoronmy fingerfelt like anencumbrance, so Itookitoff.After a time, Iheaved again, mydiaphragm

convulsing. Nurse R.explained that dry-heaving precedes themain event. I wasnowdesperateforthistobeover.The nausea began

coming in intensewaves, crashing overmeandthenreceding.I kept feeling like Iwas going to vomit,but then I would

heave noisily againand nothing wouldcome up. Severaltimes Icouldactuallyfeel my stomachconvulse.ButIwouldheaveand…nothingwouldhappen.Mysenseoftimeatthispointgetsblurry.During each bout ofretching, I wouldbegin perspiring

profusely, and whenthe nausea wouldpass, I would bedrippingwithsweat.Ifelt faint, and Iworried that I wouldpass out and vomitand aspirate and die.When I mentionedfeeling light-headed,NurseR.saidthatmycolor looked good.ButIthoughtsheand

Dr. M. seemedslightlyalarmed.Thisincreased my anxiety—becauseiftheywereworried,thenIshouldreally be scared, Ithought. (On theother hand, at somelevel Iwanted topassout, even if thatmeantdying.)After about fortyminutes and several

more bouts ofretching, Dr. M. andNurse R. suggested Itakemoreipecac.ButIfearedaseconddosewould subject me toworse nausea for alongerperiodoftime.IworriedImight justkeep dry-heaving forhours or days. Atsome point, Iswitchedfromhoping

that I would vomitquickly and have theordeal over with tothinkingthatmaybeIcouldfighttheipecacand simply wait forthe nausea to wearoff. I was exhausted,horribly nauseated,andutterlymiserable.In between bouts ofretching, I lay on thebathroom tiles,

shaking.A long periodpassed. Nurse R. andDr.M. kept trying toconvince me to takemore ipecac, but bynow I just wanted toavoid vomiting. Ihadn’t retched for awhile, so I wassurprised to bestricken by anotherbout of violent

heaving. I could feelmy stomach turningover, and I thoughtforsurethatthistimesomething wouldhappen. It didn’t. Ichoked down somesecondarywaves,andthenthenauseaeasedsignificantly.Thiswasthe point when Ibegan to feel hopefulthat I would manage

to escape the ordealwithoutthrowingup.Nurse R. seemed

angry. “Man, youhave more controlthananyoneI’veeverseen,” she said. (Atone point, she askedpeevishly if I wasresisting because Iwasn’t prepared toterminate treatmentyet.Dr.M.interjected

that this was clearlynot the case—I’dtaken the ipecac, forGod’s sake.)Eventually—severalhours had nowelapsed since Iingested the ipecac—Nurse R. left, sayingshe had never seensomeone take ipecacandnotvomit.‡After some more

time passed, andsome moreencouragement fromDr. M. to try to“complete theexposure,” wedecided to “end theattempt.” I still feltnauseated,but lesssothan before. Wetalked briefly in heroffice,andthenIleft.Driving home, I

became extremelyanxious that I wouldvomit and crash. Iwaitedatredlightsinterror.WhenIgothome,Icrawled into bed andslept for severalhours. I felt betterwhen I woke up; thenauseawasgone.Butthat night I hadrecurring nightmares

of retching in thebathroom in thebasement of thecenter.Thenextmorning Imanaged to get towork for ameeting—butthenpanicsurgedandIhadtogohome.For the next severaldays, I was tooanxious to leave thehouse.

Dr.M.called thenextdayto make sure I was okay.She clearly felt bad abouthaving subjected me tosuch a miserableexperience. Though I wastraumatized by the wholeepisode, her sense of guiltwas sopalpable that I feltsympathetic toward her.AttheendoftheaccountIcomposed at her request,whichwas accurate as far

as it went, I masked theemotionalrealityofwhatIthought (which was thatthe exposure had been anabject disaster and thatNurse R. was a fatuousbitch) with an antisepticclinical tone. “Given myhistory,Iwasbravetotakethe ipecac,” I wrote. “Iwish that I had vomitedquickly. But the wholeexperience was traumatic,

and my general anxietylevels—and my phobia ofvomiting—are moreintense than they werebeforetheexposure.Ialso,however, recognize that,basedonthisexperienceinresisting the effects of theipecac, my power toprevent myself fromvomitingisquitestrong.”Stronger, it seems, thanDr. M.’s. She told me she

had to cancel all of herafternoonappointmentsonthe day of the exposure—watching me gagging andfighting with the ipecacevidentlyhadmadehersonauseated that she spentthe afternoon at home,throwing up. I confess Itook some perversepleasure from the ironyhere—the ipecac I tookmadesomeoneelsevomit—

but mainly I felttraumatized and intenselyanxious. It seems I’m notvery good at getting overmyphobiasbutquitegoodat making my therapistsandtheirassociatessick.I continued seeing Dr.

M. fora fewmoremonths—we “processed” thebotched exposure andthen,bothofuswantingtoforget the whole thing,

turned from emetophobiato various other phobiasand neuroses—but thesessions now had anelegiac,desultory feel.Webothknewitwasover.§

That sphincter whichserves to discharge ourstomachs has dilationsand contractionsproper to itself,independent of our

wishes, and evenopposedtothem.—MICHELDEMONTAIGNE,“ONTHEPOWEROFTHEIMAGINATION”(1574)

The mind, as theneurophilosophers say, isfully embodied; it is, asAristotle put it,“enmattered.” The bodilyclichés of nervous

excitement (“butterflies inthe stomach”), anxiousanticipation (“a looseningof the bowels,” “scaredshitless”),ordread(felt“inthe pit of the stomach”)are not in fact clichés oreven metaphors buttruisms—accuratedescriptions of thephysiological correlates ofanxious emotion. Doctorsand philosophers have

observed formillennia thepotency of what themedical journals call thebrain-gutaxis.“Theremayeven be some connectionbetween a phobia and abeef-steak, so intimatelyrelated are the stomachand the brain,” WilfredNorthfieldwrotein1934.Nerve-disordered belliesare a bane of modernexistence. According to a

Harvard Medical Schoolreport, as many as 12percentofallpatientvisitstoprimarycarephysiciansintheUnitedStatesareforirritable bowel syndrome,or IBS, a conditioncharacterized by stomachpainandalternatingboutsof constipation anddiarrhea thatmost expertsbelieve to be wholly orpartly caused by stress or

anxiety. First identified in1830 by the Britishphysician John Howship,IBS has since then beenreferred to as “spasticcolon,” “spastic bowel,”“colitis,” and “functionalbowel disease,” amongother names. (Physiciansin the Middle Ages andRenaissance referred to itas “windy melancholy”and “hypochondriache

flatulence.”) Because noone has ever definitivelyidentifiedanorganiccauseof IBS, most doctorsattribute its appearance tostress, emotional conflict,or some otherpsychological source. Inthe absence of a clearmalfunction in the nervesand muscles of the gut,doctors tend to assume amalfunctioninthebrain—

perhaps a hypersensitizedawarenessof sensations inthe intestine. In one well-known set of experiments,when balloons wereinflated in the colons ofboth IBS patients andhealthy control subjects,theIBSpatientsreportedamuch lower threshold forpain, suggesting that theviscera–brain connectionmay be more sensitive in

patients with irritablebowels.This isconsistentwithatrait called anxietysensitivity,which researchhas shown to be stronglycorrelated with panicdisorder. Individuals whorate high on the so-calledAnxiety Sensitivity Index,orASI,haveahighdegreeof what’s known asinteroceptive awareness,

meaning they are highlyattuned to the innerworkings of their bodies,to the beepings andbleatings, the blips andburps, of theirphysiologies; they aremore conscious of theirheart rate, bloodpressure,body temperature,breathing rates, digestiveburblings, and so forththanotherpeopleare.This

hyperawareness ofphysiological activitymakes such people moreprone to “internally cuedpanic attacks”: theindividualwithahighASIratingpicksuponasubtleincrease inheart rateor aslight sensation ofdizziness or a vague,unidentifiable fluttering inthe chest; this perception,in turn,producesa frisson

ofconsciousanxiety(AmIhaving a heart attack?),which causes thosephysical sensations tointensify. The individualimmediatelyperceives thisintensificationofsensation—which in turn generatesmore anxiety, whichproduces still moreintensified sensations, andbefore long the individualisinthethroesofpanic.A

number of recent studiespublished in periodicalslike the Journal ofPsychosomatic Researchhave found a powerfulinterrelationship amonganxiety sensitivity,irritable bowel syndrome,worry, and a personalitytrait known asneuroticism, whichpsychologistsdefineasyouwould expect—a tendency

todwellonthenegative;ahigh susceptibility toexcessive feelings ofanxiety, guilt, anddepression; and apredispositiontooverreactto minor stress.Unsurprisingly, peoplewho score high oncognitive measures ofneuroticism aredisproportionately proneto developing phobias,

panic disorder, anddepression. (People whoscore low on theneuroticism scale aredisproportionatelyresistant to thosedisorders.)Evidence suggests thatpeople with irritablebowels have bodies thatare more physicallyreactive to stress. Irecently came across an

article in the medicaljournalGut that explainedthe circular relationshipbetween cognition (yourconscious thought) andphysiological correlates(what your body does inresponse to that thought):people who are lessanxious tend to haveminds thatdon’toverreactto stress and bodies thatdon’t overreact to stress

when their mindsexperience it, whileclinically anxious peopletend to have sensitivemindsinsensitivebodies—smallamountsofstresssetthem to worrying, andsmallamountsofworryingset their bodies tomalfunctioning. Peoplewithnervousstomachsarealso more likely thanpeople with settled

stomachs to complain ofheadaches, palpitations,shortness of breath, andgeneral fatigue. Someevidence suggests thatpeoplewithirritablebowelsyndrome have greatersensitivity to pain, aremore likely to complainabout minor ailments likecolds, and aremore likelytoconsiderthemselvessickthanotherpeople.

Most cases of stomachupset, the physiologistWalterCannonwrotebackin 1909, are “nervous inorigin.” Inhisarticle“TheInfluence of EmotionalStates on the Functions ofthe Alimentary Canal,”Cannon concluded thatanxious thoughts haddirecteffects—throughthenerves of the sympatheticnervous system—on both

thephysicalmovementsofthe stomach (that is, onperistalsis, the process bywhichthedigestivesystemmoves food through thealimentary canal) andgastric secretions.Cannon’s theory has beenborne out by modernsurveys conducted atprimary care centers,which find that mostroutine stomach trouble

emanates from mentaldistress: between 42 and61 percent of all patientswith functional boweldisorders have also beengiven an officialpsychiatricdiagnosis,mostoften anxiety ordepression; one study hasfounda40percentoverlapbetween patients withpanic disorder andfunctionalGIdisease.‖

“Fear brings aboutdiarrhea,” Aristotle wrote,“because the emotioncauses an augmenting ofheat in the belly.”Hippocrates attributedboth bowel trouble andanxiety (not to mentionhemorrhoids and acne) toa surplus of black bile.Galen, the ancient Romanphysician, blamed yellowbile. “People attacked by

fear experience no slightinflow of yellow bile intothestomach,”heobserved,“whichmakes them feel agnawing sensation, andthey do not cease feelingboth distress of mind andthe gnawing until theyhavevomitedupthebile.”Butitwasonlyin1833,

with the publication of amonograph calledExperiments and

Observations on the GastricJuice and the Physiology ofDigestion, that the linkbetween emotional statesand indigestion began tobe understood with anykindofscientificprecision.OnJune6,1822,AlexisSt.Martin,ahunteremployedby the American FurCompany,wasaccidentallyshot in the stomach atclose range by a musket

loadedwithbuckshot.Hewas expected to die—butunder the care ofWilliamBeaumont, a physician inupstate New York, hesurvived, albeit with anunusual condition: anunhealed open hole, orfistula, in his stomach.Beaumontrealizedthatthehunter’s fistula provided aremarkable opportunityfor scientific observation:

he could literally see intoSt.Martin’s stomach.Overthenextdecade,Beaumontconducted manyexperiments using thehunter’s fistula as awindow into his digestiveworkings.Beaumont noticed thatSt. Martin’s emotionalstates had a powerfuleffectonhis stomach,onereadily observable to the

naked eye: the mucosallining of the hunter’sstomach would changecolor dramatically, like amoodring,intandemwithhis emotional states.Sometimes the stomachlining was bright red; atother times, such aswhenSt. Martin was anxious, itturnedpale.“Ihaveavailedmyselfof

the opportunity afforded

by an occurrence ofcircumstances which canprobably never occuragain,” Beaumont wrote.Buthewaswrong.Medicalliterature records at leasttwo subsequent instancesof digestion researchconductedonpatientswithholes in their stomachsoverthecourseofthenextcentury. And then, in1941, Stewart Wolf and

HaroldWolff,physiciansatNew York Hospital inManhattan, discoveredTom.One day in 1904, when

Tom was nine years old,hetookaswigofwhathethought was beer (it wasin his father’s beer pail)but turned out to beboiling hot clam chowder.The chowder seared hisupper digestive tract and

knocked him unconscious.By the time his motherdelivered him to thehospital, his esophagushad fused shut. For therest of his life, the onlyway for him to receivenourishment was throughasurgicallyopenedholeinthestomachwall.Theholewas ringed on the outsideby a segment of hisstomach lining. He fed

himself by chewing hisfood and then inserting itdirectly into his stomachthroughafunnelplacedintheholeinhisabdomen.Tom came to theattentionofDrs.Wolf andWolff in 1941, when,while working as a sewerlaborer, hewas compelledto seekmedical assistanceafter his wound becameirritated. Recognizing the

unusual researchopportunityrepresentedbyTom’s condition, thedoctorshiredhimasa labassistant and conductedmultiple experiments onhim over the course ofseven months. The resultswere published in their1943 book,HumanGastricFunction, a landmark ofpsychosomaticresearch.Building on Beaumont’s

findings, the doctorsobservedthattheliningofTom’s stomach variedsignificantlyincolorbasedon its level of activity—from “faint yellowish redto adeep cardinal shade.”Greater levels of digestiveactivitytendedtocorrelatewith deeper shades of red(suggesting increasedblood flow to thestomach), while lesser

levels, including thoseinduced by anxiety,correlated with palercolors(suggestingtheflowof blood away from thestomach).Thedoctorswereableto

chartcorrelationsthathadlong been assumed butwere never scientificallyproved. One afternoonanotherdoctorbargedintothe lab, swearing to

himself and rapidlyopening and closingdrawers, looking fordocuments that had beenmislaid.Tom,whosejobitwas to keep the lab tidy,became alarmed—hefeared he would lose hisjob. The lining of hisstomach went instantlypale, dropping from “90percent redness” on thecolor scale to 20 percent.

Acid secretion nearlystopped. When the doctorfoundthemissingpapersafew minutes later, acidsecretion resumedand thecolorgraduallyreturnedtoTom’sstomach.Atsomelevel,all this isunsurprising; everyoneknows that anxiety cancause gastrointestinaldistress. (My friend Annesaysthatthemosteffective

weight-loss program sheevertriedwastheStressfulDivorce Diet.) But HumanGastric Functionrepresented the first timethat the connections hadbeen charted in suchprecise and systematicdetail. The relationshipbetween Tom’s mentalstateandhisdigestionwasnot vague and diffuse; hisstomach was a concrete

and direct register of hispsychology. Summing uptheir observations, Wolfand Wolff concluded thattherewasa strong inversecorrelation between whatthey called “emotionalsecurity” and stomachdiscomfort.That’s certainly true in

my case. Being anxiousmakes my stomach hurtandmybowelsloosen.My

stomach hurting and mybowels loosening makesme more anxious, whichmakes my stomach hurtmoreandmybowelsevenlooser,andsonearlyeverytrip of any significantdistance from home endsupthesameway:withmescurrying frantically fromrestroom to restroomonakind of grand tour of thelocallatrines.Forinstance,

I don’t have terribly vividrecollectionsoftheVaticanor the Colosseum or theItalian rail system. I do,however, have searingmemories of the publicrestrooms in the Vaticanand at the Colosseum andin various Italian trainstations.Oneday,Ivisitedthe Trevi Fountain—or,rather, my wife and herfamily visited the Trevi

Fountain. I visited therestroom of a nearbygelateria,wherea seriesofimpatient Italians bangedon the door while Ibivouackedthere.Thenextday, when the familydrove to Pompeii, I gaveup and stayed in bed, areassuringly shortdistancefromthebathroom.Some years earlier,

following the fall of the

Berlin Wall and thedissolution of the WarsawPact, I traveled to EasternEuropetovisitagirlfriend,Ann,whowas studying inPoland. She had beenthereforsixmonthsbythetime I visited; I hadplanned and aborted(because of anxiety)severalprevious trips, andonly the fear that Annwould finally break up

withmeifIdidn’tvisitherimpelled me to fightthrough my tremendousdread of a transatlanticflight to meet her inWarsaw. Drugged to nearunconsciousness, I flewfrom Boston to Londonand then to Warsaw.Befogged by sedatives,antiemetic medications,and jet lag, I stumbledthroughourfirstdayanda

half together. My bowelspercolatedtolifeaboutthetime the rest of me did,when the Dramamine andXanaxworeoff.Weendedup traipsing aroundEastern Europe fromrestroomtorestroom.Thiswasfrustratingforherandharrowing for me—because, among otherreasons, many EasternEuropean public

commodes were at thattime rather primitive; youoften had to pay anattendant in advanceon aper sheet basis forscratchy, ill-constructedtoiletpaper.Bytheendofthe trip, I’dgivenup;Annwent sightseeing while Iretreated to our hotelroom, where at least Ididn’t have to gauge mytoilet tissue use in

advance.Ann, understandably,

grew peevish about this.After visiting the home ofFranz Kafka (who, I note,suffered from chronicboweltrouble),wewalkedacrossWenceslasSquareinPrague while I gripedabout my aching belly.Ann could no longercontain her exasperation.“Maybeyoushouldwritea

dissertation about yourstomach,” she said,mocking mypreoccupation. Apreoccupation, you mayhave noticed, that I haveyettoovercome.But when your stomachgovernsyourexistence,it’shardnottobepreoccupiedwith it. A few searingexperiences—soilingyourself on an airplane,

say, or on a date—willfocus you passionately onyour gastrointestinal tract.You need to devote effortto planning around it—because itwill not alwaysplanaroundyou.Case in point: Fifteenyears ago, whileresearchingmy first book,Ispentpartofthesummerliving with the extendedKennedy family on Cape

Cod. One weekend, then–presidentBillClinton,whowas vacationing onMartha’s Vineyard, cameacrossNantucketSoundtogo sailing with TedKennedy. Hyannis Port,where the Kennedys havetheir vacation homes,wascrawling with presidentialaides and Secret Serviceagents.With some time tokill before dinner, I

decided to walk aroundtowntotakeinthescene.Bad idea. As is so often

the case with irritablebowelsyndrome, itwasatprecisely the moment Ipassed beyond EasilyAccessible BathroomRange that my cloggedplumbing came unglued.Sprinting back to thehousewhereIwasstaying,I was several times

convinced I would notmakeitand—teethgritted,sweating voluminously—was reduced to evaluatingvariousbushesandstoragesheds along the way fortheir potential as ersatzouthouses.Imaginingwhatmight ensue if a SecretService agent were tohappenuponmecrouchedin the shrubbery lent akind of panicked,

otherworldly strength tomy efforts at self-possession.As I approached the

entrance, I wassimultaneously reviewingthe floor plan inmy head(Which of the manybathroomsinthemansionisclosest to the front door?Can I make it all the wayupstairs to my room?) andpraying that Iwouldn’tbe

fatally waylaid by a strayKennedy or celebrity(Arnold Schwarzenegger,Liza Minnelli, and thesecretary of the navy,among others, werevisitingthatweekend).Fortunately, I made itintothehouseunaccosted.Then a quick calculation:Can I make it all the wayupstairs and down the hallto my suite in time? Or

should I duck into thebathroom in the front hall?Hearing footsteps aboveand fearing a protractedencounter, I opted for thelatter and slipped into thebathroom, which wasseparated from the fronthall by an anteroom andtwo separate doors. Iscampered through theanteroomandflungmyselfontothetoilet.

My relief wasextravagant and almostmetaphysical.But then I flushed

and … somethinghappened. My feet weregettingwet.Ilookeddownandsawtomyhorrorthatwater was flowing outfromthebaseofthetoilet.Somethingseemedtohaveexploded.Thefloor—alongwith my shoes and pants

and underwear—wascovered in sewage. Thewaterlevelwasrising.Instinctively, I stood up

and turned around. Couldthe floodingbe stopped? Iremoved theporcelain topof the toilet tank,scattering the flowers andpotpourri that sat atop it,and frantically beganfiddlingwith its innards. Itriedthingsblindly,raising

this and lowering that,jiggling this and wigglingthat, fishingaround in thewater for something thatmight stem the swellingtide.Somehow,whetherofits

own accord or as a resultof my haphazard fiddling,the flooding slowed andthen stopped. I surveyedthescene.Myclothesweredrenched and soiled. So

was the bathroom rug.Withoutthinking,Islippedoutofmypantsandboxershorts, wrapped them inthe waterlogged rug, andjammed the whole messinto the wastebasket,which I stashed in thecupboard under the sink.Havetodealwith this later,Ithoughttomyself.It was at thisunpropitious moment that

the dinner bell rang,signaling that it was timeto muster for cocktails inthelivingroom.Which was right acrossthe hall from thebathroom.Where I was standingankle-deepinsewage.I pulled all the handtowels off the wall anddropped them on thegroundtostartsoppingup

someof the toiletwater. Igotdownonmyhandsandknees and, unraveling thewhole roll of toilet paper,began dabbing frenziedlyatthewateraroundme.Itwas like trying to dry alake with a kitchensponge.What I was feeling at

thatpointwasnot,strictlyspeaking, anxiety; rather,it was a resigned sense

that the jig was up, thatmy humiliation would becomplete and total. I’dsoiled myself, destroyedthe estate’s septic system,and might soon bestandinghalfnakedbeforeGod knows how manymembers of the politicalandHollywoodelite.In the distance, voices

were moving closer. Itoccurred tome that I had

two choices. I couldhunker down in thebathroom, hiding andwaiting out the cocktailparty and dinner—at therisk of having to fend offanyone who might startbanging on the door—andusethetimetotrytocleanup the wreckage beforeslippinguptomybedroomaftereveryonehadgonetobed.OrIcouldtrytomake

abreakforit.I took all of the soiled

towels and toilet paperand shoved them into thecupboard, then set aboutpreparing my escape. Iretrieved the least soiledtowel (which wasnonetheless dirty andsodden) and wrapped itgingerly aroundmywaist.I crept to the door andlistened for voices and

footsteps, trying to gaugedistance and speed ofapproach. Knowing I hadscarcely any time beforeeveryoneconvergedonthecenter of the house, Islipped out the bathroomdoor and through theanteroom, sprint-walkedacross the hallway, anddarted up the stairs. I hitthe first landing, made ahairpin turn, and headed

up the next flight to thesecond floor—where Inearly ran headlong intoJohn F. Kennedy Jr. andanotherman.“Hi, Scott,” Kennedy

said.a“Uh, hi,” I said, racking

my brain for a plausibleexplanation for why Imight be running throughthehouse at cocktail hourwith no pants on,

drenched in sweat,swaddled in a soiled andreeking towel. But he andhisfriendappearedutterlyunfazed—as though half-nakedhouseguestscoveredin their own excrementwere frequent occurrenceshere—andwalkedpastmedownthestairs.I scrambled down thehallway to my room,where I showered

vigorously, changed, andgenerallytriedtocomposemyself as best I could—which was not easybecause I was continuingto sweat terribly, rightthrough my blazer, theresult of anxiety, exertion,andsummerhumidity.If someonehadsnappeda photo of the scene atcocktails that evening,here’swhatitwouldshow:

various celebrities andpoliticians and priests allglowing with grace andeasy bonhomie as theymingle effortlessly on theveranda overlooking theAtlantic—while, justoff tothe side, a sweaty youngwriter stands awkwardlygulpingginandtonicsandthinkingabouthow farheis from fitting inwith thisillustrious crowd and

about how not only is henot rich or famous oraccomplished orparticularly good-lookingbuthecannotevencontrolhis own bowels andtherefore is better suitedfor the company ofanimals or infants than ofadults, let alone adults asluminous and significantasthese.Thesweatyyoungwriter

is also worrying aboutwhat will happen whensomeone tries to use thehallwaybathroom.Late that night, after

everyone had gone off tobed, I sneaked back downto the bathroom with agarbage bag and papertowels and cleaningdetergent I’d purloinedfromthepantry.Icouldn’ttell whether anyone had

beentheresinceI left,butI triednot toworry aboutthat and concentrated onstuffing thesoiledrugandtowels and clothes andtoilet paper I’d stashedunder the sink into thetrashbag.ThenIusedthepaper towels to scrub thefloors,andIputthoseintothetrashbagaswell.Outside the kitchen,

between the main house

and an outbuilding,was aDumpster.Myplanwastodispose of everythingthere. Naturally, I wasterrifiedof getting caught.What, exactly, would ahouseguest be doingdisposing of a large trashbag outside in the middleof the night? (I worriedthat there might still beSecret Service afoot, whomight shoot me before

allowingmetoplantwhatlooked like a bomb or abodyintheDumpster.)Butwhat choice did I have? Islunk through the houseand out to the Dumpster,whereIdepositedthetrashbag. Then I went backupstairstobed.No one ever said

anything to me about thehallway bathroom orabout themissing rugand

towels. But for the rest ofthe weekend, and on mysubsequent visits there, Iwas convinced that thehousehold staff wereglaring at me andwhispering.“That’shim,”Iimaginedtheyweresayingin disgust. “The one whobrokethetoiletandruinedour towels. The one whocan’t control his ownbodilyfunctions.”b

Most persons with asore colon are of atense,sensitive,nervoustemperament. Theymay be calmexternally, but theyusually seetheinternally.—WALTERC.ALVAREZ,Nervousness,

Indigestion,andPain(1943)

Of course, I know thatsuch shame should notattach to what is,officially, a medicalcondition. Irritable bowelsyndrome is a commongastrointestinal complaintfrequently associated withmood and anxietydisorders, as has beenobserved since ancienttimes. In 1943, theeminent gastroenterologist

Walter Alvarez noted inhis delightfully titledNervousness, Indigestion,and Pain that there is nomore reason a personshouldfeelashamedabouta nervous stomach thansomeone should feelashamed at blushing at acompliment orweeping ata sad play. Thenervousness andhypersensitivity that such

physicalreactionsproduce,Alvarez wrote, areassociatedwithpersonalitytraits that, if “properlyused and controlled,” can“do much to help a mansucceed.”cButanervousstomachisbad enough—what’s mostdisablingtome is thatmynervous stomach itselfmakes me nervous. That’sthe infernal thing about

being an anxiousemetophobe: the very factofone’sstomachhurtingisitself often themost acutesource of fear. Any timeyour stomach hurts, youworry you might vomit.Thus being anxiousmakesyour stomach hurt, andyour stomach hurtingmakes you anxious—which in turnmakes yourstomachhurtmore,which

makes you more anxious,andsoonandsoforthinavicious cycle that hurtlesrapidly toward panic. Thelives of emetophobes arelargely built around theirphobia—some have notworkedorlefttheirhousesfor years because of theirfearsandcannotbearevento sayorwrite “vomit”orrelated words. (Onlineemetophobia communities

usually have rulesrequiring that such wordsbe rendered as, forinstance,“v**.”)Until recent years,

emetophobia rarelyappeared in the clinicalliterature. But the arrivalof the Internet provided ameans for emetophobes,many of whom hadpreviously believed theywere alone in their

affliction, to find oneother.d Onlinecommunities and supportgroups sprouted. Theappearanceofthesevirtualcommunities, some ofwhich are quite large (byoneestimate,theforumofthe InternationalEmetophobia Society hasfive times as manymembers as the largestflying phobia forum),

came to the attention ofanxiety researchers, whohave started to study thisphobia moresystematically.Like all anxiety

disorders, emetophobiapresents with elevatedlevels of physiologicalarousal, avoidancebehavior (and also whatexperts call safety, orneutralizing, behavior, by

which they mean doingwhat I do: carryingstomach remedies andantianxietymedications incase of emergency),attention disruption(meaning that in thepresence of a phobicstimulus, such as a virusgoingaround theofficeorthroughthefamily,wecanconcentrate on little else),and, typically, problems

with self-esteem and self-efficacy. We emetophobestend to think poorly ofourselves and to believewe have trouble copingwith the world, andespecially with somethingas catastrophic-seeming asvomiting.eAs we’ve seen, both

patients with panicdisorder andpatientswithirritable bowel syndrome

(whomuchofthetimearethe same patients) havewhatmentalhealthexpertscall “high somatizationvulnerability” (that is, atendency to convertemotional distress intophysical symptoms) and“cognitive biases in thediscrimination andinterpretation of bodilysymptoms” (that is, theyareespeciallyconsciousof

even minor changes inphysiology and have anattendantpredispositiontointerpret those symptomsin a catastrophic, worst-case-scenario way). Butwhereas the primaryconcern for most panicpatients tends to be thatanxious bodily symptomsaugur a heart attack orsuffocation or insanity ordeath, emetophobes are

afraid that the symptomsforetellimminentvomiting(and also insanity anddeath). And whereas thefears of the panic patientsare,exceptinrarecasesofanxiety-induced suddencardiac death, extremelyunlikely to be realized,emetophobes are quitecapable of bringing on,through their anxioussymptoms, the very thing

they fear most. Which, ofcourse, is another reasonto be constantly afraid ofbeing constantly afraid. Isit any wonder thatsometimes I feel like mybrainisturninginsideout?Psychologists havedeveloped severalstandardized scales formeasuring control-freakiness—there is, forinstance, Rotter’s Locus of

Control Scale andalso theHealth Locus of ControlScale. That anxiety anddepression are bound uptightly not only with self-esteem issues but withcontrol issues (anxietydisorderpatientstendbothtofeelliketheydon’thavemuch control over theirlives and to be afraid oflosing control of theirbodiesor theirminds)has

been thoroughlyestablished by generationsof researchers—but thatconnection seems to beespecially pronounced inpeople with emetophobia.A study published in theJournal of ClinicalPsychology observed that“emetophobics appearcompletely unable tonegate their insatiabledesireforthemaintenance

ofcontrol.”fDr. W. has pointed out

what he believes is theobvious multilayeredsymbolism of myemetophobia. Vomitingrepresentsalossofcontrolandalsomyfearoflettingmy insides out, ofrevealingwhat’sinsideme.Most of all, he says, itrepresents my fear ofdeath. Vomiting, and my

unruly nervous stomachgenerally, are inarguableevidence of myembodiedness—andconsequently of mymortality.gSomeday I’m going to

vomit; someday I’m goingtodie.Am I wrong to live in

quiveringterrorofboth?

I find the noodle and

the stomach areantagonistic powers.Whatthoughthastodowith digesting roastbeef, I cannot say, butthey are brotherfaculties.—CHARLESDARWINTOHISSISTERCAROLINE

(1838)

Itrytodrawsolacefrom

the knowledge that I amhardly alone in havingbothamindandabellysoeasily perturbed byanxiety. Observers goingback to Aristotle havenoted that nervousdyspepsia and intellectualaccomplishment often gohand in hand. SigmundFreud’s trip to the UnitedStates in 1909, whichintroduced psychoanalysis

to this country, wasmarred (as hewould laterfrequently complain) byhis nervous stomach andboutsofdiarrhea.Manyofthe letters betweenWilliamandHenryJames,first-class neurotics both,consist mainly of theexchange of variousremediesfortheirstomachtrouble.But for debilitating

nervous stomachcomplaints, nothingcompares to that whichafflicted poor CharlesDarwin, who spentdecades of his lifeprostrated by his upsetstomach.In 1865, he wrote a

desperate letter to aphysician named JohnChapman,listingthearrayof symptoms that had

plagued him for nearlythirtyyears:

Age 56–57.—For 25years extremespasmodic daily &nightly flatulence:occasional vomiting,on two occasionsprolonged duringmonths. Vomitingpreceded byshivering, hysterical

crying[,] dyingsensations or half-faint. & copious verypalid urine. Nowvomiting & everypassage of flatulencepreceded by ringingof ears, treading onair & vision.… Nervousness whenE[mma Darwin, hiswife]leavesme.

Eventhis listof symptomsis incomplete. At theurging of another doctor,Darwin had from July 1,1849,toJanuary16,1855,kept a “Diary of Health,”which eventually ran todozensofpagesand listedsuchcomplaintsaschronicfatigue, severe stomachpain and flatulence,frequent vomiting,dizziness (“swimming

head,” as Darwindescribed it), trembling,insomnia, rashes, eczema,boils, heart palpitationsandpain,andmelancholy.Darwin was frustrated

that dozens of physicians,beginning with his ownfather, had failed to curehim.Bythetimehewroteto Dr. Chapman, Darwinhadspentmostofthepastthree decades—during

which time he’d struggledheroically to writeOn theOrigin of Species—housebound by generalinvalidism. Based on hisdiariesand letters, it’s fairtosayhespentafullthirdofhisdaytimehours sincethe age of twenty-eighteithervomitingorlyinginbed.Chapman had treated

many prominent Victorian

intellectuals who were“knockedup”withanxietyatonetimeoranother;hespecializedin,asheputit,thosehigh-strungneurotics“whose minds are highlycultivated and developed,and often complicated,modified, and dominatedby subtle psychicalinfluences,whoseintensityand bearing on thephysical malady it is

difficulttoapprehend.”Heprescribed the applicationoficetothespinalcordforalmost all diseases ofnervousorigin.Chapman came out to

Darwin’s country estate inlate May 1865, andDarwinspentseveralhourseach day over the nextseveralmonths encased inice; he composed crucialsectionsofTheVariationof

Animals and Plants UnderDomesticationwithicebagspackedaroundhisspine.The treatment didn’t

work. The “incessantvomiting” continued. Sowhile Darwin and hisfamily enjoyed Chapman’scompany (“We liked Dr.Chapmansoverymuchwewere quite sorry the icefailed for his sake as wellas ours,” Darwin’s wife

wrote), by July they hadabandoned the treatmentandsentthedoctorbacktoLondon.Chapman was not the

first doctor to fail to cureDarwin,andhewouldnotbe the last. To readDarwin’s diaries andcorrespondence is tomarvelatthemoreor lessconstant debilitation heendured after he returned

fromthefamousvoyageofthe Beagle in 1836. Themedical debate aboutwhat, exactly, was wrongwithDarwinhasraged for150 years. The listproposed during his lifeandafterhisdeathislong:amoebic infection,appendicitis, duodenalulcer, peptic ulcer,migraines, chroniccholecystitis,“smouldering

hepatitis,” malaria,catarrhal dyspepsia,arsenic poisoning,porphyria, narcolepsy,“diabetogenichyperinsulism,” gout,“suppressed gout,”hchronic brucellosis(endemic to Argentina,which the Beagle hadvisited), Chagas’ disease(possibly contracted froma bug bite in Argentina),

allergic reactions to thepigeons he worked with,complications from theprotracted seasickness heexperiencedon theBeagle,and“refractiveanomalyoftheeyes.”I’vejustreadanarticle, “Darwin’s IllnessRevealed,” published in aBritishacademicjournalin2005, that attributesDarwin’s ailments tolactoseintolerance.i

But a careful reading ofDarwin’s life suggests thatthe precipitating factor inevery one of his mostacuteattacksofillnesswasanxiety. According toRalph Colp, a psychiatristand historian who in the1970s combed through allthe available Darwinjournals, letters, andmedical accounts, theworst periods of illness

corresponded with stresseither about his work onthe theory of evolution orabout his family. (Theanticipation of hiswedding produced a “badheadache,whichcontinuestwo days and two nights,so that I doubtedwhetherit evermeant toallowmetobemarried.”)Ina1997articlefromTheJournalofthe American Medical

Association called “CharlesDarwin and PanicDisorder,” two doctorsargue that, according tohis own account of hissymptoms, Darwin wouldeasilyqualifyfortheDSM-IV’s diagnosis of panicdisorder with agoraphobiasince he demonstratednine of the thirteensymptoms associated withit. (Only four symptoms

arerequiredtoreceivethediagnosis.)jThe voyage of the

Beagle,fouryearsandninemonthslong,wasapivotalexperience, enablingDarwin to develop hisscientific work.k Themonthsinportpriortothelaunchof theBeaglewere,as Darwin would write inhis old age, “the mostmiserable which I ever

spent”—and that’s sayingsomething, given theterrible physical sufferinghewouldlaterendure.“I was out of spirits at

the thought of leaving allmy family and friends forso long a time, and theweather seemed to meinexpressibly gloomy,” herecalled. “I was alsotroubled with palpitationsand pain about the heart,

and like many a youngignorant man, especiallyone with a smattering ofmedical knowledge, wasconvinced I had heartdisease.” He also sufferedfromfaintnessandtinglinginhisfingers.Theseareallsymptomsofanxiety—andin particular of thehyperventilationassociated with panicdisorder.

Darwinforcedhimselftoovercome his low spiritsandembarkonthevoyage,and though he was besetby both claustrophobia(which put him in“continual fear”) andgrievous seasickness, hewasmostlyhealthyon thetrip, gathering theevidence on which hewouldmakehisnameandbuild his life’s work. But

after theBeagle docked inFalmouth, England, onOctober 2, 1836, Darwinwouldneveragainsetfootoutside England. Afternearly five years oftraveling, Darwin foundhis geographical ambitincreasinglycircumscribed. “I dreadgoing anywhere, onaccount ofmy stomach soeasily failing under any

excitement,” he told hiscousin.It’s remarkable that On

the Origin of Species evergotwritten.Soonafterhismarriage, when Darwinwas beginning in earnesthis work on evolution, hesuffered the first of hismanyepisodesof“periodicvomiting,”stretcheswherehe would vomit multipletimes daily and be

bedridden for weeks—or,inseveralcases,years—onend. Excitement orsocializing of any kindcouldthrowhimintogreatphysical upheaval. Partiesor meetings would leavehim “knocked up” withanxiety, bringing on“violent shivering andvomitingattacks.”(“Ihavetherefore been compelledformanyyears to giveup

all dinner-parties,” hewrote.) He installed amirror outside his studywindow so he could seeguestscomingupthedrivebefore they saw him,allowinghimtimetobracehimselfortohide.In addition to Dr.

Chapman’s ice treatment,Darwin tried the “watercure” of the famous Dr.James Gully (who also

treated Alfred Tennyson,Thomas Carlyle, andCharles Dickens aroundthis time), exercise, asugar-freediet,brandyand“Indian ale,” chemicalconcoctions (scores ofthem), metal platesstrapped to his torsomeant to galvanize hisinsides and “electricchains”(madeofbrassandzinc wires) meant to

electrify him, anddrenching his skin withvinegar. Whether theresultoftheplaceboeffect,distraction, or actualefficacy,someofthesesortof worked some of thetime. But always theillnessreturned.Adaytripto London or any milddisturbance in his well-ordered routine wouldbringon“averybadform

of vomiting” that wouldsend him to bed for daysor weeks. Any work,especially on Origin—“myabominable volume,” asDarwin called it—couldlayhimlowformonths.“Ihavebeenbad,havingtwodays of bad vomitingowing to the accursedProofs,” he wrote to afriend inearly1859whilegoing over printer’s

corrections.He installed aspecial lavatory in hisstudy where he couldvomitbehindacurtain.Hefinished with the proofsamid fits of vomiting onOctober1,1859,endingafifteen-month periodduring which he hadrarely been able to workfreeofstomachdiscomfortfor more than twentyminutesatatime.

When On the Origin ofSpecies, more than twentyyears in gestation, wasfinally published inNovember 1859, Darwinwas laid up in bed at ahydropathy spa inYorkshire, his stomach inas much tumult as ever,his skin aflame. “I havebeen very bad lately,” hewrote. “Had an awful‘crisis’—onelegswelledup

like elephantiasis—eyesalmostclosedup—coveredwith a rash and fieryBoils… it was like livinginHell.”lDarwin continued in

poorhealth evenafter thebook’spublication.“Ishallgotomygrave,Isuppose,grumbling and growlingwith daily, almost hourly,discomfort,” he wrote in1860. Those who argue

that Darwin suffered fromsome germ-based orstructural disease point tothe severity and durationof his symptoms. (“I musttellyouhowillCharleshasbeen,”hiswifewrote toafamilyfriendinMay1864.“He has had almost dailyvomiting for 6 months.”)But in rebuttal there isthis: When Darwin wouldstopworkingandgoriding

or walking in the ScottishHighlandsorNorthWales,his health would berestored.

Charles is too muchgiventoanxiety,asyouknow.—EMMADARWINTOAFRIEND(1851)

If I seem unduly

preoccupiedwithDarwin’sstomach, perhaps you canunderstand why. It seemsboth apt and ironic thatthe man responsible forlaunching the modernstudy of fear—and foridentifying it as anemotion with concretephysiological, andespecially gastrointestinal,effects—was himself somiserably afflicted by a

nervousstomach.Thenthereisthematter

of his excessivedependence on his wife,Emma. “Without you,whenIfeelsickIfeelmostdesolate,” hewrote to heratonepoint.“OMammyIdo long to bewith you&underyourprotectionandthen I feel safe,”hewroteatanother.Mammy? No wonder

some Freudians wouldlater argue that Darwinhad dependency issues, aswell as Oedipal ones. Isupposethisistheplacetosay that—based on myburdensome overrelianceon my wife and, beforethat, on my parents—Dr.W.hasdiagnosedmewithdependent personalitydisorder, which is,according to the DSM-V,

characterized by excessivepsychological dependenceon other people (mostoften a loved one orcaretaker) and the beliefthatoneisinadequateandhelpless to cope on one’sown.Finally, of course, thereis the matter of Darwin’sdecades of constantvomiting. For anemetophobe like me, this

holdsamorbidfascination.His anxiety producedvomiting,yethisvomitingdid not (or so it seems)produce additionalanxiety.Moreover,Darwinlived, despite his years ofvomiting, to the old-for-the-time age of seventy-three. Shouldn’t Darwin’saccomplishments indefiance of such adebilitating

gastrointestinal afflictionprovide reassurance thatif,say,Iweretothrowupjust once, or even fivetimes,orevenfivetimesina day—or even, likeDarwin, five times a dayfor years on end—Imightnot only survive butperhaps even remainproductive?If you’re not an

emetophobe, this question

surely seems impossiblystrange—patent evidenceof the irrational obsessionat the core of my mentalillness. And you’re right.But if you are anemetophobe—well, then,youknowexactlywhatI’mtalkingabout.

* On the other hand, a lot of theevidence suggests that phobic

anxiety is much more easilyformedthanextinguished.Barlowhimself has a phobia of heightsthat he admits he has beenunabletocurehimselfof.

†Incidentally,theveryexistenceofthesevomitvideos—andI’venowseen several—is evidenceofhowcommon emetophobia is; usingthem has become commonpracticeintreatingphobics.Sometherapists also try to graduallydecondition their emetophobic

patientsbyexposingthemtofakevomit. (In caseyou’re interested,here’s a recipe recommended bytwo Emory Universitypsychologists I met at aconference in2008:Mixonecanofbeefandbarleysoupwithonecanofcreamofmushroomsoup.Add small quantities of sweetrelish and vinegar. Pour into aglass jar, seal, and leave on awindowsillforoneweek.)

‡ I’ve since read that up to 15

percent of people—adisproportionatenumberof thememetophobes—don’t vomit fromasingledoseofipecac.

§ Eventually, she moved away,accepting a tenure-track facultyposition at a university in theSouthwest. I run into heroccasionally at academicconferences on anxiety. Despiteeverything, I like her. But Ialwayswonder:doesitfeelweirdto her to be talking to a former

patient who’s now at theseconferences with a notebook,posingasa journalistandakindof lay expert on anxiety? Howoften does she think, That’s theguy I gave ipecac to, the guy Iwatched retching and weeping andshaking on the floor of a publicrestroomforhours?

‖ As further evidence that a greatdeal of stomach trouble starts inthe brain, not in the gut, nostomachmedicationhasyetbeen

proved consistently effectiveagainst thesymptomsof irritablebowel syndrome—but substantialevidence suggests that certainantidepressant medications canbe effective. (Before the 1960s,one of the most frequentprescriptions for IBS was acocktail of morphine andbarbiturates.) In a recent study,IBS patients injected with theSSRI antidepressant Celexareported reduced “visceral

hypersensitivity.”

MichaelGershon,aprofessorofpathology and cell biology atColumbia University, says thatthereasonantidepressantsreduceIBS symptoms is not that theyaffect neurotransmitters in thebrain but that they affectneurotransmittersinthestomach.Some95percentoftheserotonininourbodiescanbefoundinourstomachs. (When serotonin wasdiscovered in the 1930s, it was

originally called enteraminebecauseof itshighconcentrationin the gut.) Gershon calls thestomach “the second brain” andobserves that stomach trouble isas likely to beget anxiety as theotherway around. “The brain inthe bowel has got to work rightornoonewillhavetheluxurytothink at all,” he says. “No onethinks straight when hismind isfocusedonthetoilet.”

aI’djustmethimforthefirsttime

the day before. “I’m JohnKennedy,” he had said when heextended his hand inintroduction. I know, I hadthought as I extended mine,thinking it funny that he had topretend courteously that peoplemight not know his name,wheninfactonlyahermitoraMartianwouldn’t have known who hewas, so ubiquitous was his faceonthecoverofcheckoutcountermagazines.

b As bad as my own agoraphobicbelly sometimes seems to me,others have itworse.One of themore alarming case studies I’vecome across was of a forty-five-year-oldmanwhoshowedupatamental health clinic inKalamazoo, Michigan, in 2007.Hehadbeensufferingfromacutetravel anxiety for twenty years,eversincethetimeapanicattackcaused him to vomit and losecontrolofhisbowels.Sincethen,

the man had not been able totravel more than ten miles fromhome without experiencinguncontrollable vomiting anddiarrhea.Clinicians latermappedhis comfort zone by hissymptoms:thefartherfromhomehe went, the more dramatic hiseruptions. So violent were hisgastrointestinal reactions that onseveral occasions he had to berushed to emergency roomsbecause he was vomiting blood.

After physicians ruled out ulcersand stomach cancer, he wasfinallyreferredtothepsychologyclinic, and he was, his therapisttold me when I met him at aconference in 2008, successfullytreated with a combination ofexposure therapy and cognitive-behavioraltherapy.

c Alvarez observed that the mostcommon source of his patients’chronic stomach discomfort wasthe “challenges of modern

living”: “The stomach specialisthas tobeapsychiatristof sorts,”hewrote. “Hemust spend hourseach week trying to teachneurotic persons to live moresensibly.”

One young woman wasreferredtoAlvarezaftervomiting“dayandnightforaweek.”Whenhe learned that she had recentlyreceived an ominous letter fromthe Internal Revenue Service, hetreated her by paying her back

taxes—it turned out she owedonly $3.85—and she wasinstantly cured. Another patient,whom Alvarez described as “atense,high-pressure typeof salesmanager,” came to him becausehe lovedpokerbut couldn’t playit: If he got a good hand, hewould become “nauseated andchilly” and his face would turnred. Bluffing was impossiblebecauseany timehewasdealt afull house or better, he would

immediately have to get up andvomit.But“thecruelestprankofnature”Alvarezeversawwastheway nervous stomachs coulddestroy the love lives of theanxious. He treated one womanwho would get stomach crampsand have to move her bowelswhenever she was touched by aman, another who belcheduncontrollably whenever a datebecame intimate, and numerousotherswhowouldbreakwindor

vomit in romantic moments. (Inhismemoirs, the legendary loverCasanova reported on hisescapades with a woman who,whenever she became sexuallyexcited, would pass largequantities of gas.) Alvarez alsotreated “several men who weredivorced by outraged wivesbecause of their having to stopand run to the toilet whenevertheybecamesexuallyexcited.”

d According to emerging research

data, emetophobes also tend todemonstrate “a heightenedsensitivity to the opinions ofothers.”

e Among celebrities who havereported themselves to beemetophobic are the actressNicole Kidman, the musicianJoan Baez, and Matt Lauer, thehostoftheTodayshow.

fIoncedatedawomanwhoseaunthadfordecadesbeenafull-blownbulimic. From her teens into

sometime in her thirties, mygirlfriend’saunthadmadeherselfvomit after most meals. To me,this was as fascinating as it wasunfathomable. Someone wouldactually choose to make herselfvomit? I had known aboutanorexiaandbulimiasincejuniorhigh, when I’d watched after-schoolspecialsaboutthemonTV,buthadn’ttomyknowledgeevermet anyone who voluntarilyregurgitated on a regular basis.

My whole life was built aroundtrying not to vomit—and herewas someone who vomited, allthe time, by choice? True, thisperson was mentally ill, easilydiagnosable according to theDSM: “Bulimia: Eating, in adiscrete period of time, anamount of food that is definitelylarger than most people wouldeat during a similar period oftime and under similarcircumstances [combined with]

recurrent inappropriatecompensatory behavior topreventweight gain [such as] 1.Self-induced vomiting.” Butwasn’t I also, according to theverysameauthority,ill?“Phobia:A. Marked and persistent fearthatisexcessiveorunreasonable,cued by the presence oranticipationofaspecificobjectorsituation. B. Exposure to thephobicstimulusalmostinvariablyprovokes an immediate anxiety

response, which may take theform of a situationally bound orsituationally predisposed panicattack.”

Even at the time, it struckmethat our disorders were oddlyself-canceling. If I could get mymind to embrace the idea thatsomepeoplevomitedbychoicetomakethemselvesfeelbetter,couldthatmaybeleadmetoacceptthatvomitingwasnotsocatastrophic?And if bulimics could assimilate

someofmyhorrifiedaversion tovomiting, mightn’t that help todecondition them away from thepractice?

Amodestproposal:Whynotfilla grouphomewith bulimics andemetophobes and hope that theymodel themselves out of theirpathologies? The emetophobes,watching the bulimics makethemselves vomit routinely, willlearnthatthrowingupisnotthatbig a deal; the bulimics, seeing

the terror and disgust of theemetophobes, might beconditioned against such casualregurgitation.

And anyway, aren’t wefundamentallyboth,bulimicsandemetophobes alike, afraid of thesame thing: the loss of control?It’s not so much being fat thatanorexics fear—it’s feelingoutofcontrol, a feeling that purginghelpsthemperverselytocombat.Theybingeand then,not feeling

incontroloftheirownappetites,seektoexertdominionovertheirbodies by purging. But lockedintothiscycleofbingeandpurge,they are not really in control atall.

g As the British physician andphilosopher Raymond Tallis hasput it, “One sure-fire curefor … any whimsical orphilosophicalstanceonone’sownbody…isvomiting.…Yourbodyhasyouinitsentiregrip.…There

isakindof terror invomiting: itisashoutedreminderthatweareembodiedinanorganismthathasitsownagenda.”

h“Whatthedevilisthis‘suppressedgout’ upon which doctors fastenevery ill they cannot name,”Darwin’s friend Joseph Hookerwrote to him when informed ofthis diagnosis. “If it is suppressedhowdotheyknowitisgout?Ifitis apparent, why the devil dotheycallitsuppressed?”

i The authors, two Welshbiochemists, studied Darwin’sjournalsandhealthdiarytodrawcorrelationsbetweenhisdietandhisboutsofupsetstomach.

j In 1918, Edward J. Kempf, anearly American psychoanalyst,suggested in The PsychoanalyticReview that the trembling andeczema that afflicted Darwin’shandswereevidenceof“neurotichands”—which would, Kempfconcluded, “lead one strongly to

suspect an auto-erotic difficultythat had not been completelymastered.” Less outlandishpsychological explanationsventured in the years sinceinclude hypochondriasis,depression, repressed feelings ofguilt about his hostility towardhis father, “severe anxietyneurosis in an obsessionalcharacter, certainly muchcomplicated by genius,” and“bereavement syndrome”

produced by the loss of hismother at a very young age.(Creationistshaveseizeduponallthis with zealous aplomb,implying in one pseudoscholarlypaper I came across that theevidence of mental illnesssuggests Darwin was “psychotic”and that therefore his theory ofevolution was the product ofdelusion.)

k Darwin’s discovery of variantspecies of finches in the

Galápagos Islands wouldeventuallyprompthis realizationthatspecieswerenotfixedforalltime but rather transmuted—or,as hewould later say, evolved—overtime.

l One of Darwin’s biographers, theBritish psychoanalyst JohnBowlby, noted in the 1980s thatthesortsoferuptionsofboilsandrashesthatDarwinenduredwerethought by dermatologists to beassociated with people who

“strive to suppress their feelingsand who are given to low self-esteem and overwork.” Bowlby,like other biographers, alsoobserved that any stress or“increase in arousal, howevertrivial,” would produce physicalsymptomsinDarwin.

CHAPTER4

PerformanceAnxiety

Many lamentableeffectsthisfearcausethin men, as to be red,pale, tremble, sweat; itmakessuddencoldand

heat to come over allthebody,palpitationoftheheart,syncope,etc.It amazeth many menthat are to speak orshow themselves inpublic assemblies, orbefore some greatpersonages; as Tullyconfessed of himself,thathetrembledstillatthe beginning of hisspeech; and

Demosthenes, thatgreat orator ofGreece,beforePhilippus.—ROBERTBURTON,The

AnatomyofMelancholy(1621)

All public speaking ofmerit is characterizedbynervousness.—CICERO(FIRSTCENTURYA.D.)

I’ve finally settled on apretalk regimen thatenables me to avoid theweeks of anticipatorymisery that the approachof a public speakingengagement wouldotherwiseproduce.Let’ssayI’mspeakingtoyouatsomesortofpublicevent. Here’s what I’velikely done to prepare.Four hours or so ago, I

took my first halfmilligram of Xanax. (I’velearned that if I wait toolong to take it, mysympathetic nervoussystem goes so far intooverdrive that medicationis not enough to yank itback.)Then,aboutanhourago,Itookmysecondhalfmilligram of Xanax andperhaps twentymilligramsof Inderal. (I need the

whole milligram of XanaxplustheInderal,whichisabloodpressuremedication,or beta-blocker, thatdampens the response ofthe sympathetic nervoussystem, to keep myphysiological responses tothe anxious stimulus ofstanding in front of you—the sweating, trembling,nausea, burping, stomachcramps,andconstrictionin

mythroatandchest—fromoverwhelmingme.)Ilikelywashed those pills downwith a shot of scotch or,more likely, of vodka.Even two Xanax and anInderal are not enough tocalm my racing thoughtsand to keepmy chest andthroatfromconstrictingtothe point where I cannotspeak; I need the alcoholtoslowthingsdownandto

dampen the residualphysiological eruptionsthat the drugs areinadequate to contain. Infact, I probably drankmysecond shot—yes, eventhough I might bespeaking to you at, say,nine in the morning—between fifteen and thirtyminutesago,assumingthepretalk proceedingsallowed me a moment to

sneak away for a quaff.And depending on howintimidatinganaudience Ianticipated you would be,I might have made thatsecond shot a double or atriple. If the usual patternhas held, as I stand uphere talking to you now,I’vegotsomeXanaxinonepocket (in case I felt theneed to pop another onebefore being introduced)

and a minibar-size bottleor two of vodka in theother. I have been knownto take a discreet last-secondswigwhilewalkingonstage—because even asI’m still experiencing theanxiety that makes mewant to drink more, myinhibition has beenlowered,andmyjudgmentimpaired, by the liquorand benzodiazepines I’ve

already consumed. If I’vemanaged to hit the sweetspot—that perfectcombinationoftiminganddosage where thecognitiveandpsychomotorsedatingeffectofthedrugsand alcohol balances outthe physiologicalhyperarousal of theanxiety—then I’mprobably doing okay uphere: nervous but not

miserable; a little fuzzybut still able to conveyclarity; the anxiogeniceffects of this situation(me, speaking in front ofpeople) counteracted bythe anxiolytic effects ofwhat I’ve consumed.* Butif I’ve overshot on themedication—too muchXanax or liquor—I mayseem loopy or slurring orotherwiseimpaired.Andif

I didn’t self-medicateenough?Well, then,eitherI’m miserable andprobably sweatingprofusely, with my voicequavering weakly and myattention folding in uponitself,or,morelikely,Iranoffstage before I got thisfar.I know. My method ofdealing with my publicspeaking anxiety is not

healthy. It’s evidence ofalcoholism; it’s dangerous.But itworks.Onlywhen Iam sedated to nearstupefaction by acombination ofbenzodiazepines andalcohol do I feel(relatively) confident inmy ability to speak inpublic effectively andwithoutmisery.AslongasIknowthatI’llhaveaccess

to my Xanax and liquor,I’ll suffer only moderateanxiety for days before aspeech, rather thanmiserable, sleepless dreadformonths.Self-medicating,

sometimesdangerously so,is a time-honored way ofwarding off performanceanxiety. Starting when hewas thirty, WilliamGladstone, the long-

serving British primeminister, would drinklaudanum—opiumdissolved in alcohol—withhis coffee before speechesin Parliament. (Once, heaccidentallyoverdosedandhad togo toa sanatoriumto recover.) WilliamWilberforce, the famouseighteenth-century Britishantislaverypolitician,tookopium as a “calmer of

nerves” before all hisspeeches in Parliament.“Tothat,”Wilberforcesaidof his prespeech opiumregimen, “I owe mysuccess as a publicspeaker.”† LaurenceOlivier, convinced that hewas about to be driven towhathewassurewouldbereported as a “mystifyingand scandalously suddenretirement” by his stage

fright, finally confided hisdistress to the actressDameSybilThorndikeandherhusband.“Take drugs, darling,”

Thorndike told him. “Wedo.”‡

I try to draw solace fromwhat Ihave learnedaboutGladstone, Olivier, andother successful and

exalted people who havebeen debilitated by theirstagefright.Demosthenes, a Greek

statesman renowned forhis oratorical skills, was,early in his career, jeeredfor his anxious,stammering performances.Cicero, the great Romanstatesman andphilosopher, once frozewhile speaking during an

important trial in theForumandranoffstage.“Iturnpaleattheoutsetofaspeechandquakeineverylimb and in all my soul,”hewrote.Moses,accordingto various interpretationsofExodus4:10,hadafearofpublicspeakingorwasastutterer;heovercamethistobecomethevoiceofhispeople.Every era of history

seemstoofferupexamplesof prominent,accomplished figures whomanaged—or didn’tmanage—to overcomecrippling public speakinganxiety. On the morningbefore William Cowper,the eighteenth-centuryBritishpoet,wastoappearbefore theHouse of Lordsto discuss hisqualifications for a

government position, hetried to hang himself,preferring to die ratherthan endure a publicappearance. (The suicideattempt failed, and theinterview was postponed.)“They…towhomapublicexamination of themselveson any occasion is mortalpoison may have someidea of the horrors of mysituation,” Cowper wrote.

“Otherscanhavenone.”In1889,ayoungIndian

lawyer froze during hisfirst case before a judgeand ran from thecourtroom in humiliation.“Myheadwas reelingandI felt as though thewholecourtwasdoing likewise,”the lawyer would writelater,afterhehadbecomeknown as MahatmaGandhi. “I could think of

no question to ask.”Another time, whenGandhi stood up to readremarks he had preparedfor a small gathering of alocalvegetariansociety,hefound he could not speak.“MyvisionbecameblurredandItrembled,thoughthespeech hardly covered asheet of foolscap,” herecounted. What Gandhicalled “the awful strainof

publicspeaking”preventedhim for years fromspeaking up even atfriendlydinnerpartiesandnearly deterred him fromdeveloping into thespiritual leader heultimately became.ThomasJefferson,too,hadhislawcareerdisruptedbya fear of public speaking.One of his biographersnotes that if he tried to

declaim loudly, his voicewould“sinkinhisthroat.”HeneverspokeduringthedeliberationsoftheSecondContinental Congress and,remarkably, he gave onlytwo public speeches—hisinaugural addresses—during his years asPresident. After reviewingJefferson’s biographies,psychiatrists at DukeUniversity, writing in the

Journal of Nervous andMental Disease, diagnosedhim posthumously withsocialphobia.The novelist HenryJames dropped out of lawschoolaftergivingwhathefelt was an embarrassingperformance in a mootcourtcompetitioninwhichhe “quavered andcollapsed into silence”;thereafter, he avoided

making formal publicpresentations, despitebeing known for hiswittydinner party repartee.Vladimir Horowitz,perhaps the most talentedconcert pianist of thetwentieth century,developed stage fright soacutethatforfifteenyearshe refused to perform inpublic. When he finallyreturned to the stage, he

did so only on thecondition that he couldclearly see his personalphysician sitting in thefront row of the audienceatalltimes.Barbra Streisand

developed overwhelmingperformanceanxietyattheheight of her career; fortwenty-seven years sherefused to perform formoney, appearing live

only at charity events,where she believed thepressure on her was lessintense. Carly Simonabandoned the stage forseven years aftercollapsing from nervesbeforeaconcertinfrontoften thousand people inPittsburgh in 1981. Whenshe resumed performing,shewouldsometimesdriveneedles into her skin or

askherband to spankherbefore going onstage todistract her from heranxiety. The singerDonnyOsmond quit performingfor a number of yearsbecause of panic attacks.(He is now a spokesmanfor the Anxiety andDepression Association ofAmerica.) The comedianJay Mohr tells a storyabout frantically trying to

pop a Klonopin on livetelevisiontostaveoffwhathe feared would be acareer-ending panic attackwhileperformingaskitonSaturdayNight Live. (Whatsaved Mohr on thatoccasion was not theKlonopin but thedistracting hilarity of hissketchmate Chris Farley.)A few years ago, HughGrant announced his

semiretirementfromactingbecause of the panicattacks he’d get when thecamerasstartedrolling.Hesurvived one film only byfilling himself “full oflorazepam,” the short-acting benzodiazepinewith the trade nameAtivan. “I had all thesepanic attacks,” he said.“They’re awful. I freezelike a rabbit. Can’t speak,

can’tthink,sweatinglikeabull. When I got homefromdoingthatjob,Isaidtomyself,‘Nomoreacting.End of films.’ ” RickyWilliams, who won theHeisman Trophy in 1998,retired from the NationalFootballLeagueforseveralyears because of hisanxiety; social interactionsmade him so nervous thathe would give interviews

only while wearing hisfootball helmet.§ ElfriedeJelinek, the Austriannovelist who won theNobelPrizeinLiteraturein2004,refusedtoacceptheraward in person becauseher acute social phobiamadeitimpossibletobearbeinglookedatinpublic.Cicero, Demosthenes,

Gladstone. Olivier,Streisand, Wilberforce.

Physicians and scientistsand statesmen. Oscarwinners and Heismanwinners and Nobellaureates. Gandhi andJefferson and Moses.Shouldn’t I drawconsolation from theknowledge that so manypeople so much greaterthan I am have been, attimes, undone by theirstagefright?Andshouldn’t

their ability to persevereand, in some cases, toovercome their anxietygive me hope andinspiration?

Why should thethought that others arethinkingaboutusaffectour capillarycirculation?—CHARLESDARWIN,The

ExpressionoftheEmotionsinManandAnimals(1872)

The symptoms ofperformance anxietycansometimestaketheform of what seems tobe a terrible jokecustom-designed tohumiliate.—JOHNMARSHALL,

SocialPhobia(1994)

The DSM officiallydivides social anxietydisorderintotwosubtypes:specificandgeneral.Thosepatients diagnosed withspecific social anxietydisorder have anxietyattachedtoveryparticularcircumstances, almostalways relating to someform of public

performance. By far themost common specificsocialphobiaisthefearofpublicspeaking,butothersinclude the fear of eatingin public, the fear ofwriting in public, and thefear of urinating in apublic restroom. Astartlinglylargenumberofpeople arrange their livesaroundnot eating in frontof people, or are filled

withdreadattheprospectof having to sign a checkinfrontofotherpeople,orsuffer what’s known asparuresiswhenstandingataurinal.Patients suffering fromthe general subtype ofsocialanxietydisorderfeeldistress in any socialcontext. Routine eventssuch as cocktail parties,business meetings, job

interviews, and dinnerdates can be occasion forsignificant emotionalanguish and physicalsymptoms. For the moreseverely afflicted, life canbe an unremitting misery.The most mundane socialinteraction—talking to astore clerk or engaging inwatercooler chitchat—induces a kind of terror.Many social phobics

endure lives of terriblelonelinessandprofessionalimpairment. Studies findstronglinksbetweensocialphobia and bothdepression and suicide.Social phobics are also,unsurprisingly, highlyprone to alcoholism anddrugabuse.‖The terrible irony of

socialphobiaisthatoneofthethingspeoplesuffering

fromitfearmostishavingtheir anxiety exposed—which is precisely whatthe symptoms of thisanxietyserve todo.Socialphobics worry that theirinterpersonalawkwardnessor the physicalmanifestations of anxiety—their blushing andshaking and stammeringand sweating—willsomehow reveal them to

be weak or incompetent.So they get nervous, andthen they stammer orblush, which makes themmore nervous, whichmakes them stammer andblushmore,whichpropelsthem into a vicious cycleof increasing anxiety anddeterioratingperformance.Blushing is infernal inthis regard. The first casestudy of erythrophobia

(the fear of blushing inpublic) was published in1846 by a Germanphysicianwhodescribedatwenty-one-year-oldmedical student driven tosuicide by shame over hisuncontrolled blushing. Afew years later, Darwinwould dedicate a fullchapter of The ExpressionoftheEmotionsinManandAnimals to his theory of

blushing,observinghowatthe moment of mostwanting to hide one’sanxiety, blushing betraysit.“Itisnotasimpleactofreflecting on our ownappearance but thethinkingofothersthinkingof us which excites ablush,” Darwin wrote. “Itis notorious that nothingmakes a shy person blushso much as any remark,

however slight, on hispersonalappearance.”Darwin was right: I’vehad colleagues prone tonervous blushing, andnothing makes them glowredder than to have theirblushing publiclyremarkedupon.Beforeherwedding, one suchcolleague tried multiplecombinations of drugtreatments, and even

contemplated surgery, inhopes of sparing herselfwhat she believed wouldbe intolerablehumiliation.(Every year thousands ofnervous blushers undergoan endoscopictransthoracicsympathectomy, whichinvolves destroying theganglion of a sympatheticnerve located near the ribcage.)I,whoamfortunate

not to count blushingamong one of my regularnervous symptoms,observeherandthinkhowsilly she is to believe thatblushing at her weddingwouldbehumiliating.Andthen I thinkhowashamedI was of sweating andtrembling at my ownwedding and wonder if Iam not any less silly thanshe.

Shame, perhaps, is theoperative emotion here—the engine that underliesboth the anxiety and theblushing.In1839,ThomasBurgess, a Britishphysician, argued in ThePhysiologyorMechanismofBlushing that God haddesigned blushing so that“the soul might havesovereign power ofdisplaying in the cheeks

the various internalemotions of the moralfeelings.” Blushing, hewrote, can “serve as acheckonourselves,andasa sign to others that[we’re] violating ruleswhich ought to be heldsacred.”ForBurgessasforDarwin, blushing isphysiological evidence ofbothourself-consciousnessand our sociability—a

manifestation of not onlyourawarenessofourselvesbut our sensitivity to howothersperceiveus.Later work by Darwin,as well as by modernevolutionary biologists,posits that blushing is notonly a signal from ourbodies to ourselves thatwe’re committing somekind of shameful socialtransgression(youcanfeel

yourself blush by thewarmingofyourskin)butalsoasignaltoothersthatwearefeelingmodestandself-conscious.It’sawayofshowing social deferencetohigher-rankingmembersofthespecies—anditis,asBurgess would have it, acheck on our antisocialimpulses, keeping us fromdeviating from prevailingsocial norms. Social

anxietyandtheblushingitproduces can beevolutionarily adaptive—the behavior it promotescanpreservesocialcomityand can keep us frombeing ostracized from thetribe.Though social anxietydisorder as an officialdiagnosis is relativelynewinthehistoryofpsychiatry—it was born in 1980,

when the diseasewas oneof the new anxietydisorderscarvedoutoftheold Freudian neuroses bythe third edition of theDSM—the syndrome itdescribes is age-old, andthe symptoms areconsistent from age toage.aWritingin1901,PaulHartenberg, a Frenchnovelist and psychiatrist,described a syndrome

whose constellation ofphysical and emotionalsymptoms correspondsremarkably to the DSM-Vdefinitionofsocialanxietydisorder.Thesocialphobic(timide)fearsotherpeople,lacks self-confidence, andeschews socialinteractions, Hartenbergwrote in Les timides et latimidité. In anticipation ofsocial situations,

Hartenberg’s social phobicexperiences physicalsymptomssuchasaracingheart, chills,hyperventilation,sweating,nausea, vomiting,diarrhea, trembling,difficulty speaking,choking, and shortness ofbreath, plus a dulling ofthe senses and “mentalconfusion.” The socialphobic also always feels

ashamed.Hartenbergevenanticipates the moderndistinctionbetweenpeoplewho feel anxious in allsocial situations and thosewho experience anxietyonly before publicperformances—aparticularized emotionalexperience he called trac,which he described asafflictingmanyacademics,musicians, and actors

before a lecture orperformance. (Thisexperience, Hartenbergwrites, is like vertigo orseasickness—it descendssuddenly, often withoutwarning.)Yet despite what seemsto be the consistency indescriptions of socialanxiety across themillennia, thediagnosisofsocial anxiety disorder

remains controversial insome quarters. Even afterthesyndromewasformallyinscribed in the DSM in1980, diagnoses of socialphobiaremainedrareforanumber of years. Westernpsychotherapiststendedtosee it as a predominantly“Asian disorder”—acondition that flourishedin the “shame-basedcultures” (as

anthropologists describethem) of Japan and SouthKorea,wherecorrectsocialbehavior is highly valued.(In Japanese psychiatry, acondition called Taijin-Kyofu-Sho, roughlycomparable to what wecall social anxietydisorder, has long beenone of the most frequentdiagnoses.) A cross-cultural comparison

conducted in 1994suggested that the relativeprevalenceofsocialphobiasymptoms in Japan couldbe related to “the sociallypromoted show of shameamong Japanese people.”Japanesesocietyitself, thelead researcher of thesurvey argued, could beconsidered “pseudo-sociophobic” becausefeelingsandbehaviorsthat

in the West would beconsidered psychiatricsymptoms—excessiveshame, avoidance of eyecontact, elaborate displaysof deference—are culturalnormsinJapan.bIn the United States,social anxiety disorderfound an early championin Michael Liebowitz, apsychiatrist at ColumbiaUniversitywhohadserved

on theDSM subcommitteethat brought the diseaseinto official existence. In1985, Liebowitz publishedanarticleintheArchivesofGeneral Psychiatry called“Social Anxiety—theNeglected Disorder,” inwhich he argued that thedisease was woefullyunderdiagnosed andundertreated.c After thearticle appeared, research

on social phobia began toaccreteslowly.Asrecentlyas 1994, the term “socialanxiety disorder” hadappeared only fifty timesin the popular press; fiveyears later, it hadappeared hundreds ofthousands of times. Whataccounts for thedisorder’scolonizationofthepopularimagination? Largely thissingleevent: theFoodand

Drug Administration’sapproval of Paxil for thetreatmentofsocialanxietydisorder in 1999.dSmithKline Beechamquickly launched amultimillion-dollaradvertising campaignaimedatbothpsychiatristsandthegeneralpublic.“Imagine you wereallergic to people,” wentthe text of one widely

distributed Paxil ad. “Youblush, sweat, shake—evenfind it hard to breathe.That’s what social anxietydisorder feels like.”Propelled by the suddencultural currency of thedisease—that same adclaimed that “over tenmillion Americans” weresuffering from socialanxiety disorder—prescriptions of Paxil

exploded.ThedrugpassedProzac and Zoloft tobecome the nation’s best-sellingSSRIantidepressantmedication.Before1980,noonehad

ever been diagnosed withsocial anxiety disorder;twenty years later, studieswere estimating that someten million to twentymillion Americansqualifiedforthediagnosis.

Today, the officialstatisticsfromtheNationalInstitute of Mental Healthsay that more than 10percent of Americans willsuffer from social anxietydisorder at some point intheir lifetimes—and thatsome 30 percent of thesepeople will suffer acuteforms of it. (Studies inreputablemedical journalspresentsimilarstatistics.)

No wonder there’scontroversy: from zeropatientstotensofmillionsof them in the course oflessthantwentyyears.It’seasytolayoutthecynicalplot: A squishy newpsychiatric diagnosis isinvented;initiallyveryfewpatients are deemed to beill with it. Then a drug isapproved to treat it.Suddenly diagnoses

explode. Thepharmaceutical industryreapsbillions of dollars inprofit.Moreover, these critics

say, there’s another namefor the syndromeostensibly afflicting thosewith social anxietydisorder. It’s calledshyness, a commontemperamental dispositionthat should hardly be

considered a mentalillness. In 2007,Christopher Lane, aprofessor of English atNorthwestern University,published a book-lengthversion of this argument,Shyness: How NormalBehaviorBecameaSickness,claimingthatpsychiatrists,in cahoots with thepharmaceutical industry,had succeeded in

pathologizing an ordinarycharactertrait.eOn the one hand, the

sudden explosion indiagnosesofsocialanxietydisorder surelydoes speakto the power of thepharmaceutical industry’smarketing efforts tomanufacturedemandforaproduct. Besides, somequotient of nervousnessaboutsocialinteractionsis

normal. How many of usdon’t feel some discomfortat the prospect of havingto make small talk withstrangers at a party?Whodoesn’t feel some measureof anxiety at having toperform inpublicor tobejudged by an audience?Such anxiety is healthy,even adaptive. To definesuch discomfort assomethingthatneedstobe

treated with pills is tomedicalizewhat ismerelyhuman.Allofwhichlendsweighttotheideaofsocialanxietydisorderasnothingmore thanaprofit-seekingconcoction of thepharmaceuticalindustry.Ontheotherhand,Icantell you, both fromextensive research andfrom firsthand experience,that as convincing as the

casemadebyLaneandhisfellow antipharma criticscanbe, thedistress feltbysomesocialphobicsisrealand intense. Are theresome “normally” shypeople, notmentally ill orin need of psychiatricattention, who get sweptup in thebroaddiagnosticcategory of social anxietydisorder, which has beenswollen by the profit-

seeking imperatives of thedrug companies? Surely.But are there also sociallyanxious people who canlegitimately benefit frommedication and otherforms of psychiatrictreatment—who in somecases are saved bymedication fromalcoholism, despair, andsuicide?Ithinkthereare.A few years ago, the

magazine I work forpublished an essay aboutthechallengesofbeinganintrovert. Not long afterthat, this letter arrived atmyoffice:

Ijustreadyourarticleon introversion. Ayear agomy 26-year-oldsonbemoanedthefact he was anintrovert. I assured

him he was fine, weare all quietintroverts in ourfamily. Three monthsagohe leftusanote,bought a shotgun,and killed himself. Inhis note he said hewasn’t wired right.…Hefeltanxiousandawkward aroundpeople and hecouldn’t go on.… He

wassmart,gentleandvery educated. Hehad just started aninternship dealingwith the public and Ithink it pushed himover the edge. Iwishhe had saidsomething before hebought the gun. Itseems he thought itwas his only option.This was a guy who

got nervous beforegetting his blooddrawn. You can’timagine howhorribleithasbeen.

One study has foundthat up to 23 percent ofpatients diagnosed withsocial anxiety disorderattempt suicide at somepoint.Whowantstoarguethat they are just shy or

that a drug that mighthave mitigated theirsufferingwaspurelyaplayforprofit?

No passion soeffectively robs themind of acting andreasoningasfear.—EDMUNDBURKE,APhilosophicalInquiryintotheOriginofOur

IdeasoftheSublimeandBeautiful(1756)

As best I can recall,myperformance anxietyblossomed when I waseleven. Before then, I hadmade presentations inclassandinfrontofschoolassemblies and hadexperienced only nervousexcitement. So I wasblindsided when, standing

onstageinthestarringrolein my sixth-grade class’sholiday performance ofSaint George and theDragon, IsuddenlyfoundIcouldnotspeak.It was an evening in

mid-December, and theauditoriumwasfilledwitha few dozen parents,siblings, and teachers. Iremember standingbackstage beforehand,

awaiting my cue to enterstageleft,andfeelingonlymildly nervous. Thoughit’shardformetoimaginenow, I think I was evenenjoying myself, lookingforward to the attention Iwould receive as star ofthe play. But when Iwalkedtocenterstageandlooked out into theauditoriumtoseeallthoseeyes upon me, my chest

constricted.f After a fewseconds, I foundmyself inthe grip of both physicalandemotionalpanic,andIcouldbarely speak. I ekedout a few quavering lineswithadiminishingvoice—andthenarrivedatapointwhere I could make nomore words emerge. Istopped, midsentence,feelingthatIwasabouttovomit. A few agonizing

seconds of silence tickedby until my friend Peter,whowasplayingmyvalet,bailed me out by sayinghis next line.g This surelyseemed to the audiencelike a non sequitur, but itmoved the scene to itsconclusion and mercifullygot me off the stage. Bymy next scene, thephysical symptoms of myanxietyhadabatedalittle;

at the end of the play Islew the dragon asdirected. Afterward,peoplesaid theyhad likedmyfightscene,and(outofpoliteness, I was sure)nobody remarked on myfirst scene, where it musthavelooked,atbest,likeIhad forgotten my line or,atworst, like Ihad frozeninterror.A trapdoor opened

beneath me that night.After that, publicperformances were neverthe same. At the time, Iwas singing in aprofessional boys’ choirthat appeared in churchesand auditoriums all overNew England. Concertsweretorture.Iwasnotoneof the better singers, so Ineverhadsolos;Iwasjustone of twenty-four

prepubescent boysstanding anonymouslyonstage. But everymoment was misery. I’dhold my score in front ofmy face so the audiencecouldn’tseemeandmouththewordssilently.I’dhavethat horrible chokingfeeling, and my stomachwould hurt, and I wouldfear that if I made anysound,I’dvomit.h

I quit the choir, but Icouldn’t completely avoidpublic performances—especially as my anxietiesworsened and mydefinition of public gotbroader. The next year, Iwasmakingapresentationin Mr. Hunt’s seventh-grade science class. Trueto my phobicpreoccupations, I hadchosen to do a report on

the biology of foodpoisoning. Standing at thefrontoftheclass,Ibecameoverwhelmed by dizzinessandnausea.Imadeitonlya few halting sentencesinto my presentationbefore pausing and thensqueaking plaintively, “Idon’t feel well.”Mr. Hunttold me to go sit down.“Maybe he’s got foodpoisoning!” a classmate

joked. Everyone laughedwhile I burned withhumiliation.Acoupleofyearslater,I

won a junior tennistournamentatalocalclub.Afterward, there was aluncheon banquet, wheretrophies were to be givenout. All that was requiredofmewastowalkontothedais when my name wascalled, shake the hand of

the tournament director,smile for the camera, andwalk off the dais again. Iwouldn’t even have tospeak.But as the tournament

organizers proceededdownthroughthedifferentage groups, I started totremble and sweat. Theprospect of having allthose eyes upon me wasterrifying—I was sure I

would humiliatemyself insome indeterminate way.Severalminutesbeforemyname was announced, Islipped out the back doorand ran down to abasement restroom tohide, emerging onlyseveralhourslater,whenIwassuretheluncheonhadended. (This sort ofextremeavoidantbehavioris common among social

phobics. I once cameacross a report in theclinical literature of awoman who, feigningillness,skippedacompanybanquetwhere shewas tobe given an award foroutstanding performance,because the prospect ofbeing the center ofattention made her sonervous. After she missedthe dinner, a small group

of colleagues planned amoreintimatereceptioninherhonor.Shequitherjobratherthanattend.)Once, in college, Iapplied for a fellowshipthat requiredme to sit foran interview with acommitteeofhalfadozenfaculty members, most ofwhom I was alreadyfriendlywith.Webanteredeasily before the official

proceedings began. Butwhentheinterviewstartedandtheyaskedmethefirstformal question, my chestconstricted and I couldmake no sound emergefrom my trachea. I satthere, mouth silentlygaping open and thenshutting like somekindoffish or suckling mammal.WhenfinallyIwasabletoget my voice to work, I

excused myself andscurried out, feeling thecommittee’s befuddledeyesonmyback,andthatwasthat.The problem, alas, has

persisted into adulthood.There have beenhumiliating minorcatastrophes (walkingoffstage midsentenceduring publicpresentations) and scores

of near misses (televisionshows where I’ve felt thechest constriction begin;lectures and interviewswhere the room started toswim, nausea rose in mygullet, and my voicediminished to a sicklywarble). Somehow, inmany of those near-missinstances, I’vemanaged tofight through andcontinue. But in all these

situations, even whenthey’re apparently goingwell, I feel I am living onthe razor’s edge betweensuccess and failure,adulation and humiliation—between justifying myexistenceandrevealingmyunworthinesstobealive.

People are notdisturbed by things butby the view they take

ofthem.—EPICTETUS,“ON

ANXIETY”(FIRSTCENTURYA.D.)

Why does my bodybetray me in thesesituations?Performance anxiety isnot some ethereal feelingbut rather a vivid mentalstate with concrete

physical aspects that aremeasurable in alaboratory: acceleratedheart rate, heartpalpitations, increasedlevels of epinephrine andnorepinephrine in thebloodstream, decreasedgastric motility, andelevated blood pressure.Almost everyoneexperiences a measurableautonomic nervous

responsewhileperformingin public: most peopleregisteratwo-tothreefoldincrease in the level ofnorepinephrine in theirbloodstream at thebeginning of a lecture, arushofadrenalinethatcanimproveperformance—butin social phobics thisautonomic response tendsto be more acute, and ittranslates into debilitating

physical symptoms andemotional distress. Studiesat the University ofWisconsinhavefoundthatin the run-up to a speech,socially anxiousindividuals show highactivation of their rightcerebral hemispheres,which seems to interferewith both their logicalprocessingandtheirverbalabilities—the sort of brain

freeze that young Gandhiexperienced in thecourtroom.Theexperienceof struggling to think orspeak clearly in momentsof social stress has clearbiologicalsubstrates.Cognitive-behavioral

therapistsarguethatsocialanxiety disorder is aproblem of disorderedlogic,orfaultythinking.Ifwe can correct our false

beliefs and maladaptiveattitudes—our“cognitions” or “schema,”as they say—we can curethe anxiety. Epictetus, aGreek slave and StoicphilosopherlivinginRomein the first century A.D.,was the prototype of thecognitive-behavioraltherapist. His essay “OnAnxiety,” in addition tobeing one of the earliest

contributions to theliterature of self-help,seems to be the firstattempt to connectperformance anxiety towhatwewould today callissuesofself-esteem.“When I see anyoneanxious, I say, ‘what doesthis man want?’ ”Epictetus writes. “Unlesshe wanted something orother not in his own

power, how could he stillbe anxious? A musician,for instance, feels noanxietywhileheissingingby himself; but when heappearsupon the stagehedoes, even if his voice beever so good, or he playsever so well. For what hewishes is not only to singwell but likewise to gainapplause.Butthisisnotinhis own power. In short,

wherehisskilllies,thereishis courage.” In otherwords, you can’tultimatelycontrolwhetherthe audience applauds ornot,sowhatuseisthereinworrying about it? ForEpictetus, anxiety was adisorder of desire andemotion to be overcomeby logic. If you can trainyour mind to perform thesame way whether you’re

alone or being observed,you’ll not get derailed bystagefright.Two influential

twentieth-centurypsychotherapists, AlbertEllis and Aaron Beck, thefounders of rationalemotive behavioraltherapy (REBT) andcognitive-behavioraltherapy (CBT)respectively, each argued

thatthetreatmentofsocialanxiety boils down toovercoming fear ofdisapproval. To overcomesocial anxiety, they say,youneedtoinureyourselftoneedlessshame.To this end, when Dr.

M., a practitioner in theCBTmold,wastreatingmeat Boston University’sCenter for Anxiety andRelated Disorders, she

aimed, as a therapeuticexercise, to intentionallyembarrass me. She wouldescortmetotheuniversitybookstorenextdoortotheCenter and lurk discreetlynearby while I askedpurposely dumb questionsoftheclerksortoldthemIneeded a bathroombecause I was going tothrow up. I found thisexcruciatingly awkward

and embarrassing (whichwas thewholepoint), andit didn’t really help. Butthis is standard exposuretherapy for socialphobics;a growing body ofcontrolled studies supportits effectiveness. The idea,in part, is to demonstrateto the patient thatrevealing imperfection, ordoing something stupid,need notmean the end of

the world or theunravelingoftheself.iTherapists of a more

psychoanalytic bent tendto focus on the socialphobic’s firmly held viewof himself as a deeplyflawed or disgustinghuman being devoid ofintrinsic value. KathrynZerbe, a psychiatrist inPortland, Oregon, haswritten that the social

phobic’s biggest fear isthat other people willperceive his true—andinadequate—self. For thesocial phobic, any kind ofperformance—musical,sporting, public speaking—can be terrifyingbecause failurewill revealthe weakness andinadequacywithin.Thisinturn means constantlyprojecting an image that

feels false—an image ofconfidence, competence,even perfection. Dr. W.calls this impressionmanagement, and heobserves that while it canbe a symptom of socialanxiety,it’sanevenbiggercause. Once you’veinvested in theperpetuation of a publicimage that feels untrue toyour core self, you feel

always in danger of beingexposed as a fraud: onemistake, one revelation ofanxiety or weakness, andthe façade of competenceand accomplishment isexposed forwhat it is—anartificial persona designedtohide thevulnerable selfthat lies within. Thus thestakes for any givenperformance becomeexcruciatingly high:

success means preservingthe perception of valueand esteem; failure meansexposure of the shamefulselfoneistryingsohardtohide. Impressionmanagement is exhaustingand stressful—you live inconstant fear that, as Dr.W. puts it, the house ofcards that is yourprojected self will comecrashing down around

you.

A stammering man isnever a worthless one.Physiologycantellyouwhy. It is an excess ofsensibility to thepresence of his fellowcreature, that makeshimstammer.—THOMASCARLYLE,

FROMALETTERTORALPHWALDOEMERSON

(NOVEMBER17,1843)

As early as 1901, PaulHartenberg anticipatedone of the key findings ofmodern research on socialphobics. While socialphobics are unusuallyattentive to other people’sfeelings, he wrote in Lestimides et la timidité,scrutinizing the verbalintonations, facial

expressions, and bodylanguage of theirinterlocutors for signs ofhowpeoplearereactingtothem,theyarealsoundulyconfident about theconclusions they drawbased on thoseobservations—andspecifically about thenegative conclusions theydraw. That is, socialphobics are better at

pickinguponsubtlesocialcuesthanotherpeopleare—but they tend tooverinterpretanythingthatcould be construed as anegative reaction. Sincethey are predisposed tobelieve that people won’tlike them or will reactbadly to them (they tendtohaveobsessivethoughtslike I’mboringor I’m goingtomakea foolofmyselfby

saying something stupid),they’re always seekingconfirmation of this beliefby interpreting, say, asuppressed yawn or aslight twitchof themouthas disapproval. “Highlyanxious people read facialexpressionsfasterthanlessanxious people,” says R.ChrisFraley,aprofessorofpsychology at theUniversity of Illinois,

Urbana-Champaign, “butthey are also more likelyto misread them.”Alexander Bystritsky, thedirector of the AnxietyDisorders Program atUCLA, says that whileanxiouspeopledohave“asensitive emotionalbarometer” that allowsthem to detect subtlechanges in emotion, “thisbarometer can cause them

to read too much into anexpression.”Socialphobicsare, inat

least this one respect,gifted—fasterandbetteratpickingupbehavioralcuesfrom other people, withsocial antennae sosensitive that they receivetransmissions that“normal”peoplecan’t.Puttheotherwayaround, theperception of healthy

people may be adaptivelyblunted;theymaynotpickup on the negative cues—that yawn of boredom ortwitchofdisdain—thatareinfactpresent.ArneÖhman, a Swedish

neuroscientist at UppsalaUniversitywhohaswrittenextensively about theevolutionary biology ofphobic behavior, believesthat oversensitive

emotional barometers aregenetically hardwired intosocial phobics, causingthem to be acutely awareof social status ininterpersonal interactions.ConsiderthecaseofNed,afifty-six-year-old dentistwho had been in practicefor three decades. Tooutward appearances,Nedwas successful. But whenhe showed up in a

psychiatrist’s office, Nedsaid his career had beendestroyed by his fear of“doingsomethingfoolish.”jAnxiety about doingsomethingwrong thatwilllead to social humiliationis quite common. ButNed’s fear wasinterestingly specific: hisperformance anxiety wasonly acute when workingon patients whom he

perceived—based on thekind of insurance theycarried—to have socialstatusgreater thanhedid.While he worked onMedicaidpatientsor thosewithout insurance, hisanxietywasnegligible.Butwhile treating patientswith fancy insuranceindicative of a high-statusjob,Nedwasterrifiedthathis hands would shake

visibly or that he wouldsweat excessively,revealinghisanxietytohispatients, who he believedwere immune to anxietyand (as he put it)“completelyathomeintheworld” and thereforepronetojudgeandeventoridicule him for hisweakness.Symptomsofthiskindof

status-based social anxiety

—andparticularlythefearof being exposed as“weak” relative to one’speers—appear regularly inthe psychiatric literaturegoingbackacentury.Andlots of evidence supportsÖhman’s proposition thatpeople like Ned have anawareness of social status,andofsocialslights,thatistoo finely calibrated. ANational Institute of

Mental Health studypublished in 2008 foundthat the brains of peoplewith generalized socialphobia respondeddifferently to criticismthan the brains of otherpeople. When socialphobics and healthycontrol subjects readneutral comments aboutthemselves, their brainactivity looked the same.

But when the two groupsread negative commentsabout themselves, thosediagnosed with socialanxiety disorder hadmarkedly increased bloodflow to the amygdala andthe medial prefrontalcortex—two parts of thebrain associated withanxiety and the stressresponse. The brains ofsocial phobics appear

physiologically primed tobe hyperresponsive tonegativecomments.This finding aligns withthe many studies showingthat social phobicsdemonstrate a morehyperreactive amygdalaresponsetonegativefacialexpressions. When socialphobics see faces thatappear angry, frightened,or disapproving, the

neurons in theiramygdalae fire faster andmore intensively thanthose of healthy controlsubjects. As the NIMHresearchers put it,“Generalized-social-phobia-related dysfunctionmay at least partly reflectanegativeattitude towardthe self, particularly inresponse to social stimuli,as instantiated in the

medial prefrontal cortex.”What this means, in plainEnglish, is thatshameandlow self-esteem have abiological address: theyreside, evidently, in theinterconnections betweenthe amygdala and themedialprefrontalcortex.There’s now a wholesubgenre of fMRI studiesthat demonstrate that theamygdala reacts vividly to

social stimuli notperceivedbytheconsciousmind. When individualsare placed in an fMRImachine and shownimages of faces displayingfear or anger, theiramygdalae flare withactivity. This is notsurprising: we know thattheamygdalaistheseatofthe fear response. It’s alsonotsurprisingthatneurons

in the amygdalae ofdiagnosed social phobicstend to fire morefrequently and intensivelythanthoseofotherpeoplein response to frightenedor angry faces. What issurprisingisthatallpeople—social phobics andhealthy control subjectsalike—show a markedamygdala response tophotos they are not

consciously aware ofseeing. That is, if youwatch a slide show ofinnocuous images offlowers interspersed withpicturesofscaredorangryfaces flashed so quicklyyou are not consciouslyawareofseeingthem,youramygdala will flare inresponse to the emotionalfaces—even though youdon’tknowyousawthem.

Ask the test subjects intheseexperimentswhetherthey saw the scared orangry faces and they willsay they did not; theimages flashed by tooquickly for the consciousbraintoregisterthem.Butthe amygdala, operatingwith lightning-fast acuitybeneath the level ofconscious awareness,perceives the distressing

faces and flares in thefMRI.Somesubjectsreportfeeling anxiety at thesemoments—but they can’tidentify its source. Thiswould seem to beneuroscientific evidencethatFreudwasrightaboutthe existence of theunconscious: the brainreacts powerfully tostimuli that we are notexplicitlyawareof.

Hundreds of studiesreveal an unconsciousneurobiological stressresponse to social stimuli.To cite just one, a 2008study published in theJournal of CognitiveNeuroscience found thatpeople shown images ofemotional faces for thirtymilliseconds—faster thanthe conscious mind canperceive them—

demonstrated “marked”brain responses. (Thesocially anxious had thestrongest brain responses.)Fascinatingly, when testsubjects were asked tojudge whether images ofsurprised faces werepositive or negative, theirjudgments werepowerfully affectedby thesubliminal images flashedjust beforehand:when the

imageofthesurprisedfacewas preceded by asubliminal image of anangry or scared face,subjects were much morelikely to say that thesurprised face they werelooking at was negative,expressing fear or anger;when the image of thesame surprised face waspreceded by a flashedhappy face, the test

subjects were more likelyto say the same surprisedfacewasexpressingjoy.Asone of the researchers putit, “Unconsciouslyperceived signals ofthreat … bubble up andunwittingly influencesocialjudgments.”What’s the point of

having such finely tunedsocial perceptionequipment? Why do our

brains make judgmentswe’re not consciouslyawareof?One theory is that such

“quick social judging”historically enhanced ourodds of survival. In ababoontroopora tribeofhunter-gatherers, youdon’twant tomake socialimpressionsthatwillinviteattacksfromyourpeersorcause you to be banished.

For baboons, being kickedout of the troop is oftentantamount to death: alone monkey found byanother group is likely tobesetuponandkilled.Tobe an early humanbanished from the tribewas to be both deniedaccess to communal foodsupplies and renderedvulnerable to animalpredators. Thus a certain

social sensitivity—a keenattunement towhat groupnorms demand, anawareness of socialthreats, a sense of how tosignal the deference thatwillkeepyoufromgettingpummeled by a higher-status member of yourtroop or banished fromyour tribe—is adaptive.(This is where blushingcan be helpful as an

automatic signal ofdeferencetoothers.)Beingaware of how your socialbehavior—your“performance”—is beingperceived by others canhelpyoustayalive.Callingattention to yourself andbeing judged negatively isalways risky: you’re indanger of having yourstatus challenged or ofbeing kicked out of the

tribe for making a badimpression.kMurray Stein, a

psychiatrist at theUniversity of California,San Diego, has observedthat social submissivenessin baboons and otherprimates has strikingparallels with socialphobia in humans. Thestress that social phobicsfeel in anticipation of

normal humaninteractions,andespeciallyof public performances,Stein says, produces thesamehypercortisolism—anelevation in the levels ofstress hormones and anactivation of thehypothalamic-pituitary-adrenal (HPA) axis—thatsubordinate status does inbaboons.Hypercortisolism,in turn, kindles the

amygdala, which has theeffect of both intensifyinganxietyinthemomentandtying social interactionsmore deeply to a stressresponseinthefuture.lStein’s research builds

on the work of RobertSapolsky, a neurobiologistat Stanford who has donefascinating researchshowing a directcorrelation between a

baboon’s status in histroop and the quantity ofstress hormones in hisblood.Baboonpopulationshave strictly orderedmalehierarchies: there is thealphamale,whoisusuallythe biggest and strongestandhasthemostaccesstofood and females and isdeferredtobyalltheothermale monkeys, then thereis the second-highest-

ranking monkey, who isdeferredtobyalltheothermonkeys except for thealphamale—andsoon,allthe way down to thelowest-rankingmaleatthebottom of the socialladder. If a fight breaksout between two baboonsandthehigher-rankingonewins, the social order ispreserved; if the lower-ranking onewins, there is

a re-sorting, with thevictorious baboon movingup the social ladder.Through carefulobservation, Sapolsky’steam has been able todetermine the socialhierarchies of particularbaboonpopulations.Usingblood tests from theseprimates, Sapolsky hasfound that testosteronelevels correlate directly

with social standing: thehigherrankingthebaboon,themoretestosteronehe’llhave. Moreover, when ababoon rises in the socialhierarchy, the amount oftestosterone he producesincreases; when a baboondeclines in status, histestosterone levels fall.(The causation seems towork in both directions:testosterone produces

dominance, anddominance producestestosterone.)Butjustashigherrankis

associated withtestosterone, lower rank isassociated with stresshormoneslikecortisol:thelower a baboon’s standingin the hierarchy, thegreater the concentrationof stress hormones in hisblood.Asubordinatemale

not only has to workhardertoprocurefoodandaccess to females but alsohastotreadcarefullysoasnot to get beaten up by adominant animal. It’sunclear whether highlevels of cortisol cause ababoon to becomesubmissive orwhether thestress of being low statuscauses cortisol levels torise.Mostlikelyit’sboth—

the physical andpsychological pressures ofbeing a subordinatebaboon lead to elevatedlevels of stress hormones,which produce moreanxiety, which producesmore stress hormones,which produce moresubmissiveness andgeneralillhealth.While findings fromanimal studies can be

applied to ourunderstanding of humannature only indirectly (wecan reason in ways otherprimates cannot), Ned’sanxious response topracticing dentistry on“higher-status” patientsmaywellhave its roots inprimitive concerns aboutoversteppingboundsinthestatus hierarchy. Low-ranking baboons and

orangutans that fail tolowertheireyes—tosignaltheir submissiveness—inthe presence of higher-ranking ones risk invitingattack. A baboon’s statusin the social hierarchy—and, beyond that, hisskillfulness at behaving inaccord with his rank,whatever that may be—doesalottodeterminehisphysicalwell-being.m

Both low-rankingbaboonsandhumanswithsocial anxiety disorderresort easily to submissivebehavior.Likelow-rankinganimals, people with thegeneral subtype of socialanxiety disorder tend tolookdownward,avoideyecontact,blush,andengageinbehaviorsthatadvertisetheir submissiveness,eagerly seeking to please

their peers and superiorsand actively deferring toothers to avoid conflict.For low-ranking baboons,this behavior is aprotective adaptation. Itcan be adaptive inhumans,too—butinsocialphobics it is more oftenself-defeating.Low-statusmonkeysand

socially phobic humansalso tend to have notable

irregularities in theprocessing of certainneurotransmitters. Studieshave found that monkeyswith enhancedserotonergic function (inessence, higher levels ofserotonin in their brainsynapses) tend tobemoredominant, more friendly,andmorelikelythanthosewith normal serotoninlevels to bond with their

peers. In contrast,monkeys with unusuallylow serotonin levels aremore likely to displayavoidant behavior: theykeep to themselves andavoid social interactions.Recent studies of humanshave found alteredserotonin function incertain brain regions ofpatients diagnosed withsocial anxiety disorder.

These findings helpexplain why selectiveserotonin reuptakeinhibitors like Prozac andPaxil can be effective intreating social anxiety.(Studies have also foundthat when nonanxious,nondepressed people takeSSRIs, they become morefriendly.)Dopaminehasalsobeen

implicated in shaping

social behavior. Whenmonkeys who have beenhoused alone are takenfrom their cages andplaced into a groupsetting, the monkeys thatrise the highest in thedominance hierarchy tendtohavemoredopamineintheir brains—which isinteresting in light ofstudiesfindingthatpeoplediagnosed with social

anxiety disorder tend tohave lower-than-averagedopamine levels. Somestudieshavefoundstrikingcorrelationsbetweensocialanxiety and Parkinson’sdisease, a neurologicalcondition associated witha deficit of dopamine inthebrain.One2008 studyfound that half ofParkinson’spatientsscoredhigh enough on the

Liebowitz Social AnxietyScaletobediagnosedwithsocial phobia. Multiplerecent studies have found“altereddopaminebindingpotential” in the brains ofthe socially anxious.nMurray Stein, amongothers, has hypothesizedthat the awkwardness andinterpersonalclumsinessofsocial phobics are directlyconnected to problems in

dopamine functioning; thedopamine“reinforcement/reward”pathways that help guidecorrect social behavior inhealthy people maysomehow be askew in thebrainsofsocialphobics.My sister, who has foryears suffered from socialanxiety, strongly endorsesthis view. Withoutknowing anything about

neurobiology,shehaslonginsisted that her brain is“wiredwrong.”“Social situations that

normal people breezethrough unthinkinglycause my brain to shutdown,” she says. “I cannever think of what tosay.”Though her brain

otherwise functions well(she’s a successful

cartoonist, editor, andchildren’s book authorwho graduated fromHarvard), she has, eversincejuniorhigh,wrestledwith what she calls her“talkingproblem.”Neitherdecades of psychotherapynor dozens of drugcombinations have muchalleviated it. Shehasbeenevaluated for Asperger’ssyndrome and other

disorders on the autismspectrum, but she doesn’tlack empathy the wayAsperger’spatientsdo.oThe association of

dopamine and serotoninwith social phobia doesn’tprove thatneurotransmitter deficitscausesocialanxiety—thoseirregularities could be theeffectsofsocialanxiety,theneurochemical“scars”that

develop when a brainbecomesoverstressedfromhavingtobesovigilantallthe time, constantlyscanning the environmentfor social threats. Butemergingresearchsuggeststhat the efficiency withwhich dopamine andserotoningetferriedacrossthe synapses is geneticallydetermined. Researchershave found that which

variant of the serotonintransporter gene you havedetermines the density ofserotoninreceptorsinyourneurons—and that therelative density of yourserotonin receptors helpsdetermine where you fallon the spectrum betweenshyandextroverted.pThe introduction of

social uncertainty into agroup of baboons does

interesting things to ratesof anxiety. Low-rankingbaboons are alwaysstressed. But RobertSapolsky has found thatwheneveranewmalejoinsthe troop, theglucocorticoid levels ofallthe baboons—not just thelow-rankingones—becomeelevated. With theintroduction of newmembers into a social

hierarchy, appropriaterules of conduct, such aswho should defer towhom, become unclear;there are more fights andgeneralagitation.Oncethenew baboon has beenassimilated into the tribe,stress levels andglucocorticoidconcentrations decline,andsocialbehaviorreturnstonormal.

This also happens inhumans.Inthelate1990s,Dirk Hellhammer, aGerman psychobiologist,coded sixty-three armyrecruits at boot campaccording to their relativeposition in the socialhierarchy (as determinedby anthropologicalobservation) and thenmeasured their cortisollevels every week. During

stable periods, the moredominant recruits hadlower baseline levels ofsalivary cortisol than thesubordinateones—justlikebaboons. But duringperiods of experimentallyinduced psychological andphysical stress, cortisollevels increased in all thesoldiers—markedly in thedominant subjects andmodestly in the

subordinate ones. Whileit’salwaysstressfulbeingalow-ranking member ofthe tribe, disruptions tothe social order seem tomake everyone, even thehigh-ranking members,stressed.q

Many of us havestrivedforperfectioninorder to try to controlour world.… There is

generallyadeep-seatedfeeling of not beinggood enough, of beingdeficientordefectiveinsome way, or of beingdifferentfromothersinaway thatwill not beaccepted by others.Thiscreatesafeelingofshame and a fear ofembarrassment andhumiliation inexposingyour true self in front

ofothers.—JANETESPOSITO,IntheSpotlight(2000)

Recently, while siftingthrough the records frommy treatment with Dr.M.nearly a decade ago, Icame across a documentI’d written at her request.Shehadaskedmetowritedownwhattheoutcomeof

a worst-case-scenariopublic speakingcatastrophe would be forme. The idea behind thissort of exercise is to fullyimagine the worst thingthat could happen (totalfailure, completehumiliation) and then,onceyou’vereallythoughtabout it, to conclude that,first, the worst-casescenario was unlikely to

unfoldand,second,evenifitdid,maybeitwouldnotbe so shatteringlycatastrophic. Reachingthat conclusion, andassimilating itintellectually andemotionally,issupposedtolower the stakes of theperformanceand thereforediminishanxiety.That’s the theory

anyway. But when I

showed up at mylunchtime appointmentoneThursdayafterhavinge-mailed hermy imaginedworst-casepublicspeakingscenario (humiliation andphysical collapse followedby unemployment,divorce, and ostracismfrom society), Dr. M.lookedstricken.“Your write-up,” she

said. “It’s the most

negative thing I’ve everread.”Shetoldmeshehadbeen horrified at what I’dwritten and had feltcompelled to show myaccounttoherdepartmentsupervisor in search ofmore experienced counsel.As she looked at me withsympathy, concern, and, Ibelieve, no small alarm, Isuspected she’d raised thequestion of whether I

might be gravelydepressed and possiblypsychotic.Perhaps I have an

overactive imagination;perhaps I’m undulypessimistic. But I nowknow that negativity andpoor self-image—alongwith a desperate desire toconceal that poor self-image—are textbook for asocialphobic.Nearlyevery

book on the subject, bothpopular and academic,observes that socialanxiety disorder isassociatedwith feelingsofinferiority and withextreme sensitivity to anykind of criticism ornegativeevaluation.r“Jeez,” Dr. W. said to

me one day when I wasexplainingtohimthehighstakes I ascribed to an

upcomingpubliceventandhowimportantIthoughtitwastomaintainmyfaçadeofefficacyandtohidemysense of fraudulence andweakness. “Do you realizehowpotentlyyoursenseofshame contributes to youranxiety?”BothDr.M. andDr.W.

—nottomentionEpictetus—would say that the bestcureforthiskindofsocial

anxiety is to diminish thepower of shame. Theembarrassing exposuresthat Dr. M. subjected meto were designed to inureme somewhat to feelingsofshame.“Go ahead, put it out

there,” Dr. W. says,speaking of my anxiety.“Youmay be surprised byhowpeoplerespond.“Stop caring so much

about what other peoplethink,” he says, echoingthe advice of a hundredself-helpbooks.Ifonlyitwerethateasy.

The day I’m notnervous is the day Iquit.Tome,nervesaregreat.That means youcare, and I care aboutwhatIdo.

—TIGERWOODS,ATAPRESSCONFERENCEBEFORETHE2009WGC-ACCENTUREMATCHPLAY

CHAMPIONSHIP

Idon’tgiveashitwhatyou say. If I go outthere and miss gamewinners and peoplesay, “Kobe choked” or“Kobe is seven forwhatever in pressure

situations,” well, fuckyou. Because I don’tplay for your fuckingapproval.Iplayformyown love andenjoymentofthegame.And to win. That’swhat I play for. Mostof the time,when guysfeel the pressure,they’re worried aboutwhat people might sayabout them. I don’t

have that fear, and itenables me to forgetbad plays and to takeshots and play mygame.—KOBEBRYANT,DURINGANINTERVIEWFOLLOWINGGAME3OFTHE2012NBAWESTERNCONFERENCE

SEMIFINALS

One day in seventh

grade, while playing myclassmate Paul in a tennismatch, I becomeoverwhelmed withanxiety. My stomach isdistended; I am burpinguncontrollably. Before thematch started, the mostimportantthingwasthatIwin.Butnowthat Iaminthe middle of the matchandmystomachhurtsandIamafraidofthrowingup,

the most important thingisthatIgetoffthecourtasquickly as possible. Andthequickestwaytodothatistolose.AndsoIhitballsout. I hit them into thenet. I double-fault. I lose6–1, 6–0, and when Ishake hands and get offthe court, the first thing Ifeel is relief. My stomachsettles.Myanxietyrelents.AndthenextthingIfeel

is self-loathing. Because Ihave lost to theoverweightandoleaginousPaul,whoisnowstruttingaround proudly, crowingabout how badly he hasbeatenme. The stakes arelow: it is a challengematchforoneofthelowerladder positions on themiddle-school juniorvarsity.Buttometheyfeelexistentially high. I have

lost to Paul, who is not aparticularly good player—hisskills,hisquickness,hisfitness are manifestlyworse thanmine—andtheresultisthereonthescoresheet and on the ladderhanging on the lockerroom wall and radiatingfrom Paul’s puffed-outchest,foralltosee:hehaswon, so he is superior tome. I have lost; I am

therefore, by definition, aloser.This sort of thing—

purposely losing matchesto escape intolerableanxiety—happened dozensof times throughout myschool sports career. Notevery thrown match wasas egregious as the oneagainstPaul(whosename,by the way, I havechanged here)—I often

tanked matches againstplayers who would likelyhave beaten me even if Ihadn’t sufferedananxiousmeltdown—but some ofthem were. My coacheswerebaffled.Howcoulditbe, they wondered, that Icould look so skillful inpractice and yet so rarelywinasignificantmatch?Theexceptionwastenth

grade, when I played for

the junior varsity squashteamandwentundefeated:17–0 or something.What,you might ask, accountsforthat?Valium.Squash matches, even

squash practices, weremaking me so miserablethatthechildpsychiatristIwas seeing then, Dr. L.,prescribed a small dose ofthe benzodiazepine. Every

day during squash seasonthat year, I took the pillsurreptitiously with mypeanut butter sandwich atlunch. And I didn’t lose amatch.Iwasstillunhappyduring squash season: myagoraphobia andseparation anxiety mademe hate traveling tomatches, and mycompetitive anxieties stillmade me hate playing in

them.ButtheValiumtookenough of the physicaledge off my nerves that Icould focus on trying toplay well instead of ontrying to get off the courtas quickly as possible. Ididn’t feel compelled tolose matches on purposeanymore. Drugs got meinto the zone ofperformance whereanxietyisbeneficial.

In 1908, twopsychologists, Robert M.Yerkes and JohnDillingham Dodson,publishedanarticleinTheJournal of ComparativeNeurology and Psychologydemonstrating thatanimalstrainedtoperformataskperformeditslightlybetter if they were made“moderately anxious”beforehand. This led to

what has become knownas theYerkes-Dodson law,whose principles havebeen experimentallydemonstrated in bothanimalsandhumansmanytimes since then. It’s kindof a Goldilocks law: toolittle anxiety and youwillnot perform at your peak,whether on a test or in asquash match; too muchanxiety and you will not

performwell;butwithjustthe right amount ofanxiety—enough toelevate your physiologicalarousal and to focus yourattention intensely on thetask,butnotsomuchthatyouaredistractedbyhownervousyouare—you’llbemore likely to deliver apeakperformance.Forme,evidently,gettingfromthetoo-anxious part of the

curve to the optimum-performance part requiredasmalldoseofValium.sI wish I could say

competitive anxiety wasmerely an adolescentphase.Butabouttenyearsago, I found myselfplaying in the finals of asquashtournamentagainstmy friend Jay, apersonable youngphysician. It was

championship night at thesquash club, and a coupleof dozen people hadturned out to watch. Wewere two just-better-than-average club players;absolutely nothing ofsignificance (no money,hardly a trophy to speakof)wasontheline.In this tournament,

matches were best of fivegames;towinagameyou

needed nine points. Ijumped out confidently toan early lead in the firstgame, but I let it slipaway. I won the secondgame; Jay won the third.Mybackagainstthewall,Iwon the fourth, and Jaysaggedvisibly. I could seethat he was tired—moretired than I was. In thefifth and deciding game, Ipulled steadily ahead and

got to 7–3, two pointsaway from victory. Jaylooked defeated. Victorywasmine.Exceptitwasn’t.The prospect of

imminent victory sentanxiety cascading throughmybody.Mymouthwentdry. My limbs grewimpossiblyheavy.Worstofall, my stomach betrayedme. Overwhelmed with

nausea and panic, I hitweak shots, desperateshots. Jay, momentsearlier disconsolate andresigned to losing, perkedup. I’d givenhima rayofhope. He gainedmomentum. My anxietymounted, and suddenly itwas like I was back inseventh grade, playingtennis against Paul: all Iwant is out. I withered

before everyone’s eyes. Ibegan,onpurpose,tolose.Jay seized his

opportunity, Lazarus fromthe grave, and beat me.Afterward, I tried to begracious in defeat, butwhen everyone inevitablycommented on howdramatically I had blownmy near victory, Iattributed my collapse toback trouble.Mybackdid

hurt—butitwasnotwhyIlost. I had thechampionship in myclutches, and I let it slipaway because I was tooanxioustocompete.Ichoked.Just about the worstepithetonecanslingatanathlete—worse, in someways, than “cheater”—is“choker”: to choke is towiltunderpressure,tofail

to perform at themomentof greatest importance. (Atechnicaldefinition,aslaidout by Sian Beilock, aUniversity of Chicagocognitivepsychologistwhospecializes in the topic, is“suboptimal performance—worse performance thanexpected given what aperformer is capable ofdoing and what thisperformerhasdone in the

past.”) The etymologicalstem of “anxious”—anx—comes from the Latinangere, which means “tochoke”; the Latin wordanxiusprobablyreferredtothe feeling of chestconstriction experiencedduring a panic attack. Tochoke, in an athletic orany other kind ofperformance context,implies an absence of

fortitude, a weakness ofcharacter. The mostcommon explanation forchokinginasportingeventis, in the shorthandof thesports reporter, “nerves.”Choking,inotherwords,isproduced by anxiety—andin the sporting arena, aswell as on the field ofbattleorintheworkplace,anxietyisipsofactoasignofweakness.

Sincemycollapseintheclub finals that year, Ihavelearnedthebeneficialeffects of prematchmeditation and havegotten better at titratingmydosagesofprophylacticantianxiety medication.Mywifehasalsoborneustwo children, whichshould have put intoperspective the existentialinsignificance of a

recreational sportingevent. And yet theproblempersists.Not long ago, I found

myself in thesemifinalsofanother squashtournament.“Why do you play in

these tournaments if theymake you so miserable?”Dr. W. had asked meseveral years earlier. “Ifyou can’t learn to enjoy

them, stop torturingyourself by playing inthem!”AndsoIhadstoppedfor

a while. And when Istartedagain,Ididsowitha conscious lack ofemotional investment. I’mjustdoingitfortheexercise,Itellmyself.Icanenjoythecompetition without makingmyself anxious andmiserable about the

outcome. And through thefirst rounds of thistournament, I do. Sure,there are tense moments;at times I feel pressure,which fatigues me anddiminishes the quality ofmyplay.Butthat’snormal,the vicissitudes ofcompetition; it doesn’tdebilitate me. And I keepwinning.SowhenI stepoutonto

the court for thesemifinals, I tell myself, Istill do not care. Only fivepeoplearewatching.Ilosea close first game.But it’sfun. No big deal. I don’tcare.Myopponentisgood.Ishould lose this match. Noexpectations,nopressure.But then I win the next

game. Wait a minute, Ithink. I’m in this match. Icould win it. The moment

my competitive impulsesurges, the familiarheavinessdescendsandmystomachinflateswithair.C’mon, Scott, I tell

myself. Have fun. Whocareswhowins?I try to relax but my

breathing is gettingheavier.I’msweatingmoreprofusely. And as wordspreadsthatthematchisaclose one, more people

begingatheringbehindthecourttowatch.I try to slow everything

down—my breathing, thepace of my play. As myanxietyrises,thequalityofmygamedeteriorates.ButI am still, for themomentanyway,focusingontryingto play well, on trying towin. To my surprise, myslowing-the-pace-downstrategy works: I come

from behind to win thethird game. One moregame and Iwill be in thechampionship.At which point I find Iam so enervated by myanxiety that I can nolonger play. My opponentwins the next gamequickly,eveningthematchat 2–2.Whoever wins thenextgamewillbeintothefinals.

I use the allotted two-minute break betweengames to retreat to themen’s room to try tocollect myself. I am paleand shaking—and, mostterrifying to me,nauseated.As Iwalk backout on the court, therefereeasksifIamokay.(Iclearlydonotlookwell.)Imumble that I am. Thefifthgamebegins,andIno

longer care at all aboutwinning; as in my matchagainst Paul thirty yearsearlier, I care only aboutgetting off the courtwithout vomiting. Onceagain,Istarttryingtoloseas quickly as possible: Istoprunningfortheball;Ishank balls on purpose.My opponent is puzzled.After I fail to run for aneasy drop shot, he turns

and asks me if I’m okay.Mortified,InodthatIam.ButIamnotokay.Iam

terrified that Iwill not beable to loseenoughpointsquickly enough to get offthe court before retchingandhumiliatingmyself. Inseventh grade, at least, Ihad been able to stay onthe court until the end ofthe match with Paul; thistime, with so many eyes

upon me and my gorgerising, I cannot do eventhat. Two points later,with the match manypoints from conclusion, Iraisemyhandindefeat.“Iconcede,”Isaytomy

opponent.“I’msick.”AndIscurry off the court indefeat.I have not just lost. I

havegivenup.Foldedlikea cheap lawn chair. I feel

mortifiedandpathetic.Friends in the audience

murmur words ofconsolation in mydirection. “We could tellyou weren’t feeling well,”they say. “Somethingwasn’tright.”Ishakethemoff(“Badfishfor lunch,”Imumble)andretreattothelockerroom.Asever,onceIamoutofthecompetitivemoment,andoutofpublic

view,myanxietyrecedes.But I have lost to

another opponent I mightwellhavebeaten.Intruth,I don’t really care aboutthe losing. What bothersme is that, yet again, myanxiety has defeated me,reduced me to a helplessmassofquiveringjellyandexposed me to what feelslike minor publicembarrassment.

I know: the reality isthat no one cares. Whichsomehow just makes thisallthemorepathetic.

Never in my careerhave I experiencedanything like whathappened.Iwastotallyout of control. And Icouldn’tunderstandit.—GREGNORMAN,TOGOLFMAGAZINEON

BLOWINGALARGELEADATTHE1996MASTERS

The list of elite athleteswho have chokedspectacularly,orwhohavedeveloped bizarre andcrippling performanceanxieties,isextensive.Greg Norman, the

Australian golfer, cameunglued at the 1996Masters, nervously

frittering away aseemingly insurmountablelead over the final fewholes;heendedupsobbingin the arms of the manwhobeathim,NickFaldo.Jana Novotna, the Czechtennisstar,wasfivepointsaway from winningWimbledon in 1993 whenshe disintegrated underpressure and blew a hugelead over Steffi Graf; she

ended up sobbing in thearms of the Duchess ofKent. On November 25,1980,RobertoDurán,thenthe reigning worldwelterweight boxingchampion, squared offagainstSugarRayLeonardinoneof themost famousbouts ever. With sixteenseconds left in the eighthround—and millions ofdollarsontheline—Durán

turned to the referee,raised his hands insurrender, and pleaded,“Nomás,nomás[Nomore,no more]. No more box.”He would later say hisstomach hurt. Until thatmoment, Durán wasperceived tobe invincible,the epitome of Latinomachismo. Since then, hehas lived in infamy—considered one of the

greatest quitters andcowardsinsportshistory.These are all classicchokes—mental andphysical collapses inisolated moments of highanxiety.Morepuzzlingarethose professional athleteswho, in an excruciatinglypublic manifestation ofperformance anxiety, gointo a kind of chronicchoke. In the mid-1990s,

Nick Anderson was aguard for the OrlandoMagic. He entered the1995NBAfinalsasasolidfree-throw shooter, havingmade about 70 percent ofhis foul shots throughouthis career. But in the firstgameof thechampionshipseries against theHoustonRockets that year,Anderson had fourconsecutive opportunities

to secure a victory forOrlandowithafoulshotinthe final seconds ofregulationtime:allhehadtodowashitoneshot.He missed all four. The

Magicwentontolosethatgame in overtime, andthentolosetheseriesinafour-game sweep. Afterthat, Anderson’s free-throw percentageplummeted; for the

remainderofhiscareer,hewas a disaster at the foulline. This caused him toplay less aggressively onoffense because he wasafraid he’d get fouled andhave to shoot free throws.The missed championshipfree throws, Andersonrecalledlater,were“likeasong that got inmyhead,playingoverandoverandover.” He was driven to

earlyretirement.In 1999, Chuck

Knoblauch lost the abilityto throw a baseball fromsecond to first base. Thiswould not have been aproblem had he nothappened to be, at thetime, the starting secondbasemanfortheNewYorkYankees. Knoblauch hadno physical injury thatwould have impeded him

—he could throw to firstjust fine during practice.During games, however,with forty thousand fanswatching him in thestadiumandmillionsmorewatching him ontelevision, he repeatedlyoverthrew the base,launchingtheballintothestands.Twodecadesearlier,just

ayearremovedfrombeing

named the NationalLeague’s rookie of theyear,SteveSax,thesecondbaseman for the LosAngeles Dodgers,developed the sameafflictionasKnoblauch.Hehadnotroubleinpractice,though, even successfullythrowingblindfoldedinanefforttobreakthehabit.Mostinfamouslythereis

Steve Blass, an All-Star

pitcher for the PittsburghPirateswho,inJune1973,following a stretch whenhe was perhaps the bestpitcher in baseball, wassuddenly unable to throwtheball throughthestrikezone.Inpractice,hecouldthrowaswellasever.Butduring games, he couldn’tcontrolwheretheballwasgoing. Afterpsychotherapy,

meditation, hypnotism,and all manner ofcockeyed home remedies(including wearing looserunderwear) failed to curehim,heretired.Odder still are the

examplesofMike IvieandMackey Sasser, catchersfor the San Diego Padresand New York Mets,respectively. Both becameso phobic about throwing

theballbacktothepitcher—the sort of thing LittleLeaguers do withouttrouble—that they endedup having to leave theirpositions. (The sportspsychiatristAllanLanshalfjokingly coined the term“disreturnophobia” todescribethisaffliction.)The explicit monitoring

theoryofchoking,derivedfrom recent findings in

cognitive psychology andneuroscience, holds thatperformance falters whenathletes concentrate toomuch attention on it.Thinking too much aboutwhat you are doingactually impairsperformance. This wouldseemto runcounter toallthe standard bromidesabout how the quality ofyourperformanceistiedto

theintensityofyourfocus.But what seems to matteris the type of focus youhave. Sian Beilock, whostudies the psychology ofchoking at her lab at theUniversityofChicago,saysthat actively worryingabout screwing up makesyou more likely to screwup. To achieve optimalperformance—what somepsychologists call flow—

parts of yourbrain shouldbeon automaticpilot, notactivelythinkingabout(or“explicitly monitoring”)what you are doing. Bythislogic,thereasonIvie’sand Sasser’s“disreturnophobia”becamesoseverewasthatthey were thinking toomuch about what shouldhave been the mindlessmechanicsofthrowingthe

ball back to the pitcher.(AmIgrippingtheballright?Am I following through intherightarmposition?Do Ilook funny? Am I going toscrew thisupagain?What’swrong with me?) Beilockhas found that she candramatically improveathletes’ performance (atleast in experimentalsituations)bygettingthemto focus on something

other than the mechanicsof their stroke or swing;havingthemreciteapoemor sing a song in theirhead, distracting theirconscious attention fromthe physical task, canrapidly improveperformance.But anxious people

generally can’t stopthinkingabouteverything,all the time, in all the

wrong ways.What if this?What if that? Am I doingthis right?Do I lookstupid?What if I make a fool ofmyself? What if I throw itinto the standsagain?Am Iblushing visibly?Canpeopleseeme trembling? Can theyhear my voice quavering?AmIgoingtolosemyjoborgetdemotedtotheminors?When you look at brain

scans of athletes pre- or

midchoke, says the sportspsychologist BradleyHatfield, you see a neural“traffic jam”ofworry andself-monitoring. Brainscans of nonchokers, onthe other hand—the TomBradys and PeytonMannings of the world,who exude grace underpressure—reveal neuralactivity that is “efficientand streamlined,” using

only those parts of thebrain relevant to efficientperformance.In a sense, the anxiety

exhibited by all thesechoking athletes is aversion of the blushingproblem: their fear ofembarrassing themselvesin public leads them toembarrass themselves inpublic. Their anxietydrivesthemtodothevery

thing they most fear. Themore self-conscious youare—the more susceptibleto shame—the worse youwillperform.

If you are a man youwill not permit yourself-respecttoadmitananxiety neurosis or toshowfear.—SIGNSPOSTEDONALLIEDGUNSITESIN

MALTADURINGWORLDWARII

In 1830, Colonel R.Taylor, the British consulinBaghdad,wasexploringan archaeologicalexcavation on the site ofanancientAssyrianpalacewhenhecameacrossasix-sided clay prism coveredwith cuneiform. TheTaylorprism,which today

is housed in the BritishMuseum, tells of themilitarycampaignsofKingSennacherib, who ruledAssyria in the eighthcenturyB.C. Theprismhasbeen of great value tohistorians and theologiansbecause of thecontemporaneousaccountsit provides of eventsdescribed in the OldTestament. To me,

however, the mostinteresting passage on theprism describes Assyria’sbattle with two youngkings of Elam(southwestern Iran on amodernmap).“Tosavetheirlivestheytrampled over the bodiesof their soldiersand fled,”the prism reads,recountingwhathappenedwhen Sennacherib’s army

overwhelmed them. “Likeyoung captured birds theylost their courage. Withtheir urine they defiledtheir chariots and let falltheirexcrements.”Here, in one of theearliest written recordsever discovered, is thedamningjudgmentcastonthe weak stomach andmoral character of theanxiouswarrior.

Many of the sportstropes about heroism,courage, and “graceunderpressure” are also appliedto war. But the stakesattending a sportingperformance pale besidethose attendingperformanceinwar,wherethe difference betweensuccessandfailureisoftenthedifferencebetweenlifeanddeath.

Societies grant thehighest approbation tosoldiers(andathletes)whodisplay grace underpressure—and harshlydisparage thosewho falterunder it. The anxious areinconstant and weak; thebrave are stolid andstrong. Cowards aregoverned by their fears;heroesareunperturbedbythem. In his Histories,

Herodotus tells ofAristodemus, an eliteSpartan warrior whose“heart failed him” at theBattle of Thermopylae in480 B.C.; he remained intherearguardanddidnotjoin the fight.ThenceforthAristodemus becameknown as the Trembler,and he “found himself insuch disgrace that hehangedhimself.”

Militaries have alwaysgone to considerablelength to inure theirsoldiers to anxiety. TheVikings used stimulantsmade from deer urine toprovide chemicalresistance to fear. Britishmilitary commandershistorically girded theirsoldiers with rum; theRussian army used vodka(and also valerian, a mild

tranquilizer). ThePentagon has beenresearchingpharmacological means ofshuttingdownthefight-or-flight response, with aneye toward eradicatingbattlefield fear.Researchers at JohnsHopkins Universityrecentlydesignedasystemthat would allowcommanders to monitor

their soldiers’ stress levelsin real time bymeasuringthe hormonehydrocortisone—the ideabeing that if a soldier’sstress hormones exceed acertainlevel,heshouldberemovedfrombattle.Militaries denigrate

fearful behavior for goodreason: anxiety can bedevastating to the soldierand to the army he fights

in. The Anglo-SaxonChronicle recounts thebattle between Englandand Denmark that tookplace in 1003, in whichÆlfric, the Englishcommander, became soanxious that he began tovomitandcouldnolongercommand his men, whoended up beingslaughteredbytheDanes.Anxiety can spread by

contagion, so armies seekaggressively to contain it.During the Civil War, theUnion army tattooed orbranded soldiers foundguilty of cowardice.During World War I, anyBritish soldier whodeveloped neurosis as aresult of war trauma wasdeclared to be “at best aconstitutionally inferiorhuman being, at worst a

malingererandacoward.”Medicalwritersofthetimedescribed anxious soldiersas“moralinvalids.”(Someprogressive doctors—includingW.H.R.Rivers,who treated the poetSiegfried Sassoon, amongothers—argued thatcombat neurosis was amedical condition thatcould affect even soldiersof stern moral stuff, but

such doctors were in theminority.) A 1914 articleinThe American Review ofReviewsarguedthat“panicmaybecheckedbyofficersfiring on their ownmen.”Until the Second WorldWar, the British armypunished deserters withdeath.The Second World Warwas the first conflict inwhich psychiatrists played

a significant role, both asscreenersofsoldiersbeforecombat and as healers oftheir psychic woundsafterward. More than amillion U.S. soldiers wereadmitted to hospitals forpsychiatric treatment ofbattle fatigue. But somesenior officers frettedabout what this morehumane treatment ofsoldiers meant for combat

effectiveness. GeorgeMarshall, the U.S. Armygeneral who later becamesecretary of state,lamentedthatsoldierswhoonthefrontlineswouldbeconsidered cowards andmalingerers wereconsideredbypsychiatriststo be patients. The“hyperconsiderateprofessional attitude” ofthe psychiatrist, Marshall

complained,wouldleadtoan army of cossetedcowards. British generalsstatedinreputablemedicaljournals that men whopanicked during combatshould be sterilized“because only such ameasure would preventmen from showing fearand passing on to anothergeneration their mentalweakness.” High-ranking

officers on both sides ofthe Atlantic argued thatsoldiers diagnosed with“war neurosis” should notbe allowed to poison thegene pool with theircowardice.“It isnowtimethat our country stoppedbeing soft,” one Britishcolonel declared, “andabandoned its program ofmollycoddling no-goods.”For his part, General

George Patton of the U.S.Army denied there wassuch a thing as warneurosis. He preferred theterm “combat exhaustion”and said it was a mere“problem of the will.” Inorder to prevent combatexhaustionfromspreading,Patton proposed to thecommanding general,DwightEisenhower,thatitbe punishable by death.

(Eisenhower declined toimplementthesuggestion.)Modern armies stillstruggle with what to doabout soldiers undone bytheir combat-shatterednerves. During the Iraqwar, The New York Timesreported on an Americansoldier who had beendishonorably dischargedfor cowardice. The soldiercontested his discharge,

arguing it should havebeenanhonorableone.Hewasnotacoward,hesaid,but rather a medicalpatient suffering from apsychiatric illness: thestress of war had givenhimpanic disorder,whichcaused him debilitatinganxiety attacks. He wassick, his lawyers argued,not cowardly. Themilitary, in this instance,

initially refused torecognizethedistinction—thoughArmyofficialslaterdropped the cowardicecharges, reducing them tothe lesser offense ofderelictionofduty.Throughout history

there have always beenanxious soldiers, menwhose nerve failed themandwhosebodiesbetrayedthem in crucial moments.

After his first experiencewith combat, in 1862,William Henry, a youngUnionsoldierof theSixty-Eighth PennsylvaniaVolunteers, sufferedhorriblestomachpainsanddiarrhea. Deemed by hisdoctors tobe inotherwisegood physical health,Henrywasthefirstpersonto be formally diagnosedwith “soldier’s heart,” a

syndrome brought on bythe stress of combat.tStudies of “self-soilingrates” amongU.S. soldiersduring World War IIconsistently found that 5to6percentofcombatantslost control of theirbowels,withratesinsomecombat divisionsexceeding 20 percent.Before landing on IwoJima in June 1945,

American troops sufferedrampant diarrhea; somesoldiers used this as anexcuse toavoidcombat.AsurveyofoneU.S. combatdivisioninFrance in1944revealed that more thanhalf of the soldiers brokeout in cold sweats, feltfaint, or lost control oftheirbowelsduringbattle.Another survey of WorldWar II infantrymen found

that only 7 percent saidthey never felt fear—whereas 75 percent saidtheir hands trembled, 85percent said they gotsweaty palms, 12 percentsaid they lost bowelcontrol, and 25 percentsaid they lost bladdercontrol. (Upon hearingthat a quarter of surveyrespondents admitted tolosing control of their

bladdersduringbattle,onearmy colonel said,“Hell… all that proves isthat three out of four aredamned liars!”) Recentfindings issued by thePentagon revealed that ahigh number of soldiersdeployed in Iraq vomitedfrom anxiety before goingout on patrol in combatareas.William Manchester,

who would go on tobecome an eminentAmericanhistorian,foughtat Okinawa during theSecond World War. “Icould feel a twitching inmyjaw,comingandgoinglikeawinkylightsignalingsome disorder,” he wrote,recalling his firstexperience of directcombat, in which heapproached a Japanese

sniper hiding out in ashack. “Various valveswere opening and closinginmystomach.Mymouthwasdry,my legs quaking,andmyeyesoutoffocus.”Manchestershotandkilledthe sniper—and thenvomited and urinated onhimself.“Is thiswhat theymean by ‘conspicuousgallantry’?”hewondered.I would argue that

Manchester’s anxiousphysiological reaction hadanalmostmoralqualitytoit, a sensitivity to theexistential gravity of thesituation. Anxiety, asobservers since Augustinehave noted, can beusefullyallied tomorality;people who have nophysiological reaction inthese situations are theproverbial cold-blooded

killers. As the writerChristopher Hitchens—noone’s idea of a coward—once put it, “Now, thosewho fail to registeremotion under pressureare often apparently goodofficer material, but thatvery stoicism can alsoconceal—as with officerswho don’t suffer frombattle fatigue or post-traumatic stress—a

psychopathic calm thatsends the whole platooninto aditch full of barbedwireandshedsnotears.”Nevertheless, there is a

culturally acceptedconnectionstretchingbackto ancient times betweencourage andmanliness, aswell as an approbativemoral quality assigned totheabilitytocontrolone’sbodily functions when in

extremis. Legend has itthat when Napoleonneeded a man “with ironnerve” for a dangerousmission, he orderedseveralvolunteersbeforeafake firing squad andchose the one who“showed no tendency tomove his bowels” whenfireduponwithblanks.My colleague Jeff, a

journalist who has

reported from war zonesallovertheworldandhasbeen kidnapped byterrorist organizations,says that neophyte warcorrespondents alwayswonder about what willhappen the first time theyfind themselves pinneddown by gunfire. “Untilyou’vebeenunderfire,”hesays,“thequestionyouaskyourself is, Will I shit my

pants? Some do; somedon’t.Ididn’t—andIknewfrom then on I would befine. But until it happens,youjustdon’tknow.”Happily,I’veneverbeen

firedupon.But I suspect Iknow intowhich categoryIwouldfall.

A coward changescolor all the time, andcannot sit still for

nervousness,butsquatsdown,firstononeheel,then on the other; hisheart thumps in hisbreast as he thinks ofdeath in all its forms,and one can hear thechattering of his teeth.But the brave mannever changes color atall and is not undulyperturbed, from themomentwhenhe takes

hisseatinambushwiththerest.—HOMER,THEILIAD(CIRCAEIGHTHCENTURY

B.C.)

Why do some peopleexhibit grace under firewhileothersfallsoreadilyto pieces? Studies showthat almost everyone—allbut themost resilient and

the most sociopathic—hasabreakingpoint,apsychicthresholdbeyondwhichheor she can bear no morecombat stress withoutemotional and physicaldeterioration or collapse.But some people canwithstand lots of stressbefore breaking down andcan recover from combatexhaustion quickly; othersbreak down easily and

recover slowly and withdifficulty—if they recoveratall.There seems to be

remarkable consistencyacrosshumanpopulations:a fixed percentage ofindividuals will crackunder pressure, andanother fixed percentagewill remain largelyimmune to it.Comprehensive studies

conducted during WorldWar II found that in thetypical combat unit, afairly constant proportionof men will emotionallycollapse early on, usuallyeven before getting to thebattlefield; anotherrelatively fixed proportion(someofthemsociopathic)will be able to withstandextraordinary amounts ofstress without ill effect;

and the majority of menwill fall somewherebetweentheseextremes.John Leach, a Britishpsychologist who studiescognition under extremestress, has observed that,on average, 10 to 20percent of people willremaincoolandcomposedin combat situations.“Thesepeoplewillbeableto collect their thoughts

quickly,” he writes inSurvival Psychology. “Theirawareness of the situationwill be intact and theirjudgment and reasoningabilities will not beimpairedtoanysignificantextent.” At the otherextreme, 10 to 15 percentof people will react with“uncontrolled weeping,confusion, screaming andparalyzing anxiety.” But

most people, Leach says,up to 80 percent of them,will in high-stress lethalconditions becomelethargic and confused,waitingfordirection.(Thisperhaps helps account forwhy so many peoplesubmit so readily toauthoritarianisminperiodsof extreme stress ordisruption.)On the other hand,

British psychiatristsobserved that duringWorld War II, as theLuftwafferainedbombsonLondon, civilians withpreexisting neuroticdisorders found that theirgeneral levels of anxietyactually declined. As onehistorian has written,“Neurotics turned out tobe remarkably calm aboutbeing threatened from the

skies”—probably becausethey felt reassured todiscover that “normal”people shared their fearsduring the Blitz. Onepsychiatrist speculatedthat neurotics feltreassured by the sight ofother people “looking asworried as they have feltover the years.”When it’sacceptable to feelanxious,neuroticsfeellessanxious.

One fascinatingstudyofstress duringwartimewasconductedbyV.A.Kral,adoctorwhowasheldintheconcentration campTheresienstadt duringWorldWar II. In1951,hepublishedanarticleinTheAmerican Journal ofPsychiatry reporting thatalthough thirty-threethousand people died atTheresienstadt—and

another eighty-seventhousand were transferredto other Naziconcentration camps tobekilled—no new cases ofphobia, neurosis, orpathological anxietydeveloped there. In fact,Kral, who worked at thecamp hospital, noted thatwhile most detaineesbecame depressed, fewexperienced clinical

anxiety. He wrote thatthose who had before thewar suffered from “severeand long-lastingpsychoneuroses such asphobias and compulsiveobsessive neuroses” foundthat their ailments hadgone into remission.“[Patients’]neuroseseitherdisappeared completely inTheresienstadt orimprovedtosuchadegree

that patients would workand did not have to seekmedicalaid.”Interestingly,those patients whosurvived the war relapsedinto their old neuroticpatterns afterward. It wasas though real fearcrowdedouttheirneuroticanxiety; when the fearrelented, the anxiety creptback.Military psychiatrists

havecollectedalotofdataonwhatkindsofsituationscause soldiers the greatestanxiety.Manystudieshaveshown that the amount ofcontrol a soldier feels hehas strongly determineshow much anxiety heexperiences. As RoyGrinkerandhiscolleaguesfirst described in MenUnder Stress, the classicstudy of combat neuroses

duringWorldWarII,whilefighterpilotswereterrifiedof flak shot from theground, they foundfightingwithenemyplanestobeexhilarating.uCombat trauma is a

powerful psychicdestroyer: many soldiersbreak down emotionallyduring war; still morebreak down afterward.Vietnam produced

thousands of traumatizedsoldiers, many of whomended up homeless andaddicted to drugs. Somefifty-eight thousand U.S.soldiersdiedduringactivecombat in Vietnambetween1965and1975—but an even greaternumber have committedsuicide since then. Suicideis also rampant amongveteransofourrecentwars

in Iraq and Afghanistan.According to numbersfrom the Army BehavioralHealth Integrated DataEnvironment, the suiciderate among active-dutysoldiers increased 80percentbetween2004and2008; a 2012 studypublished in InjuryPrevention reported thatthe number of suicides is“unprecedentedinover30

years of U.S. Armyrecords.” A study in TheJournal of the AmericanMedical Associationconcluded that more than10 percent of Afghanistanveterans and nearly 20percent of Iraq veteranssuffer from anxiety ordepression. Other studieshave found massive ratesof antidepressant andtranquilizer consumption

among Iraq veterans; ABCNews reports that one inthree soldiers is nowtaking psychiatricmedication. The mortalityrates for those who breakdown under combat stressare much higher than forthose who don’t: a recentstudy published in theAnnals of Epidemiologyshowedthatarmyveteransdiagnosed with post-

traumatic stress disorderhave twice the prematuredeath rate of theirunafflictedpeers.Theratesofpostcombatsuicidehavebecome so high in recentyearsthattheU.S.militaryhas made providingprophylactic treatment forpost-traumatic stressdisorderahighpriority.In2012, the suicide ratereachedaten-yearhigh—a

staggering eighteencurrent and formerservicemen are killingthemselves every day inthe United States,accordingtoAdmiralMikeMullen, the formerchairman of the JointChiefsofStaff.Of course, until 1980,

when the diagnosis wasdecreed into existencealongsidetheotheranxiety

disorders with thepublicationoftheDSM-III,there was officially nosuch thing as PTSD.v Aswith social anxietydisorder, there remainssome controversy overwhether such a thing aspost-traumatic stressdisorder really exists innature—andoverwhether,if it does, how broadly itshould be defined. These

debates inevitably getpoliticized because of thebillions of dollars at stakein veterans’ medicalbenefitsanddrugcompanyrevenues and because ofabiding tensions over thedistinction between moralcowardice and a medicalcondition.For itspart, theU.S. military today viewsPTSDasarealandseriousproblem and is dedicating

considerable resources toresearching its causes,treatment,andprevention.The Pentagon underwritesmany studies of NavySEALs, generally thetoughest, most resilientsoldiers in themilitary, touncoverwhatcombinationof genes, neurochemistry,and—especially—trainingmakes them so mentallyformidable. Experiments

have consistently foundthat SEALs think moreclearly, and make fasterand better decisions, thanothersoldiersinchaoticorstressfulsituations.

Asimportantasthenatureof the combat stress asoldier experiences is,recent findings inneuroscience and genetics

suggest that the nature ofthe soldier may be moreimportant in contributingto the likelihood of anervous breakdown.Whether you are morelikelytobreakdownundermodestcombatstressortoremain implacable evenunder extreme wartimeconditions may be largelyattributable to the neuro-chemicalsyoubringtothe

battle,andthesearepartlyaproductofyourgenes.Andy Morgan, apsychiatrist at the YaleSchool of Medicine, hasstudied the SpecialOperations Forces traineesatFortBraggwhoundergothe famous SERE(Survival, Evasion,Resistance, and Escape)program. These aspiringNavy SEALs and Green

Beretsareexposedtothreeweeks of extreme physicaland psychologicalhardship to determinewhether they couldwithstand the stress ofbeing a prisoner of war.They endure pain, sleepdeprivation, isolation, andinterrogation—including“advanced techniques”such as waterboarding.The trainees selected for

the program have alreadymade it through a coupleof years of training atplacessuchasFortBragg’sJohn F. Kennedy SpecialWarfare Center andSchool.Thephysicallyandpsychologically weak getweeded out long beforeSERE. But even for theelite troops who make itthis far, SERE can beastonishinglystressful.Ina

2001 paper, Morgan andhis collaborators notedthat recorded changes inthestresshormonecortisolduring SERE “were someof the greatest everdocumented inhumans”—greater even than thoseassociatedwithopen-heartsurgery.Morgan recently

discoveredthattheSpecialForces recruits who

performedmosteffectivelyduring SERE hadsignificantly higher levels—as much as one-thirdhigher—of a brainchemical calledneuropeptide Y than thepoorer-performing recruitsdid. Discovered in 1982,neuropeptideY(orNPY,asthe researchers call it) isthemostabundantpeptidein the brain, involved in

regulating diet andbalance—and the stressresponse.SomeindividualswithhighNPYlevelsseemcompletely immune todeveloping post-traumaticstress disorder—noamountofstresscanbreakthem. The correlationbetween NPY and stressresistanceissostrongthatMorgan has found he canpredict with remarkable

accuracy who willgraduate from SpecialForces training and whowill not simply byperforming a blood test.Those with high NPYlevelswill graduate; thosewith low levels will not.Somehow, NPY conferspsychological resistanceandresilience.wIt’spossiblethatthosein

the Special Forces who

thriveunderpressurehavelearned to be resilient—that their highNPY levelsare the product of theirtraining or theirupbringing.Resilience is atrait that can be taught;the Pentagon is spendingmillions trying to figureouthowtodo thatbetter.But studies suggest that aperson’s allotment of NPYis relatively fixed from

birth, more a function ofheredity than of learning.Researchers at theUniversity of Michiganhave found correlationsnot only between whichvariation of theNPY geneyouhaveandhowmuchofthe neurotransmitter youproduce but also betweenhow much NPY youproduceandhowintenselyyou react to negative

events. People with lowlevelsofNPYshowedmorehyperreactivity in the“negative emotioncircuits”ofthebrain(suchas the right amygdala)thanpeoplewithhighNPYlevels and were muchslower to return to calmbrain states after astressful event. They werealso more likely to havehad episodes of major

depression—and that wasindependent of anythinghaving to do with theirserotonin systems, whichis where much of theneuroscienceresearchoverthe last few decades hasbeen concentrated.Conversely, having amplequantitiesofNPYseemstoprepare you to thriveunderstress.Other research has

found that soldiers whosebodiesaremorereactivetostress hormones are morelikely to crack underpressure. A 2010 studypublished inTheAmericanJournal of Psychiatryconcluded that soldierswith more glucocorticoidreceptors in their bloodcells were at greater riskfor developing PTSD aftercombat. Studies like this

tend to validate the ideathathow likelyyouare tobreakdownunderpressureis largely determined bythe relative sensitivity ofyour hypothalamic-pituitary-adrenal axis: ifyou have a hypersensitiveHPA axis, you’re muchmore likely to developPTSD or some otheranxiety disorder in theaftermath of a traumatic

experience; if you have alow-reactiveHPAaxis,youwill be much moreresistant, if not largelyimmune, to developingPTSD.Andwhileweknowthat lots of thingsconditionthesensitivityofyourHPA axis—fromhowmuch affection yourparents gave you to yourdiet to the nature of thetrauma itself—your genes

are a major determinant.All of which suggests astrongcorrelationbetweenyour genetically conferredphysiologyandhow likelyyou are to crack understress.But if grace under

pressureislargelyamatterofthequantityofacertainpeptide in thebrain,orofyour inborn level of HPAsensitivity, what kind of

graceisthat?

The hero and thecoward both feel thesame thing, but thehero uses his fear,projects it onto hisopponent, while thecoward runs. It’s thesame thing, fear, butit’swhatyoudowithitthatmatters.

—CUSD’AMATO,BOXINGMANAGERWHOTRAINEDFLOYDPATTERSONAND

MIKETYSON

Are those of us withhypersensitive HPA axes,ourbodiessettoquiveringlike mice in response tothe mildest perturbances,doomed to falter at themoments of greatestimportance?Destined, like

Aristodemus the Tremblerand Roberto Durán, forshame and humiliation?Fatedalwaystobevictimsof our twitchy bodies andunrulyemotions?Notnecessarily.Because

when you begin tountangle the relationshipsbetween anxiety andperformance, and betweengrace and courage, theyturn out to be more

complicated than they atfirst seem. Maybe it’spossible to besimultaneously anxiousand effective, cowardlyand strong, terrified andheroic.Bill Russell is a Hall of

Fame basketball playerwho won elevenchampionships with theBostonCeltics(themostbyanyone in any major

Americansport,ever),wasselected to the NBA All-Star team twelve times,andwasvotedtheleague’smost valuable player fivetimes. He is generallyacknowledged to be thegreatest defender and all-around winner of his era,ifnotofalltime.Heistheonly athlete in history, inany sport, to win anational college

championship,anOlympicgold medal, and aprofessionalchampionship.No one would questionRussell’s toughness or hischampionship qualities orhis courage. And yet, tomy amazement, this is aman who vomited fromanxietybeforethemajorityofthegamesheplayedin.According to onetabulation, Russell

vomited before 1,128 ofhis games between 1956and 1969, which wouldput him nearly in CharlesDarwin territory.“[Russell] used to throwup all the time before agame, or at halftime,” histeammate John Havlicektold the writer GeorgePlimpton in 1968. “It’s awelcome sound, too,because it means he’s

keyedupforthegameandaroundthelockerroomwegrin and say, ‘Man, we’regoing to be all righttonight.’”Like someone with ananxiety disorder, Russellhadtocontendwithnervesthat wreaked havoc withhis stomach. But a crucialdifferencebetweenRusselland the typical anxietypatient (aside, of course,

from Russell’spreternatural athleticism)was that there was apositive correlationbetween his anxiety andhis performance—andtherefore between hisupset stomach and hisperformance. Once, in1960, when the Celtics’coach noted with concernthatRussellhadn’tvomitedyet, he ordered that the

pregame warm-up besuspended until Russellcould regurgitate. WhenRussell stopped throwingupforastretchattheendof the 1963 season, hesuffered through one ofthe worst slumps of hiscareer. Fortunately, whenthe play-offs started thatyearandhesawthecrowdgathering before theopening game, he felt his

nerves jangling, and heresumed his nervousvomiting—and then wentout and gave his bestperformanceoftheseason.For Russell, a nervousstomach correlated witheffective, even enhanced,performance.xNoriscowardicealways

necessarilyan impedimentto greatness. In 1956,FloydPatterson,attheage

oftwenty-one,becametheyoungest worldheavyweight boxingchampion. Then, in aseriesofclassicboutswithIngemar Johanssonbetween 1959 and 1961,he became the first boxerin history to regain thetitle after losing it. Thefollowing year he lost thetitle for good in a matchagainst Sonny Liston, but

he remained anintermittent contender foranother decade, fightingagainst Liston, JimmyEllis,andMuhammadAli.Pattersonwastoughand

fierce and strong—forseveral years, by dint ofbeing heavyweightchampion, probablyamong the toughest andfiercest and strongestmenin the world. Yet he was

also,byhisownaccount,acoward. After his firstdefeat by Liston, he tooktobringingdisguises—fakebeards and mustaches,hats—tohis fights, incasehe lost his nerve andwanted to slip out of thedressing room before thebout or to hide afterwardif he lost. In 1964, thewriter Gay Talese, whowasprofilingPattersonfor

Esquire, asked him abouthis penchant for carryingdisguises.“Youmustwonderwhat

makes a man do thingslike this,” Patterson said.“Well, I wonder too. Andthe answer is, I don’tknow … but I think thatwithin me, within everyhuman being, there is acertain weakness. It is aweakness that exposes

itself more when you’realone. And I have figuredoutthatpartofthereasonI do the things I do, andcannot seem to conquerthat one word—myself—isbecause… isbecause… Iamacoward.”Of course, Patterson’s

definition of cowardicemight be different fromyours or mine; it’s hardlyconventional.y But it

nevertheless suggests thatinner anxiety can becoupled with the outerappearance of physicalbravery, that weakness isnot incompatible withstrength.In rare instances,

anxiety can even be thesource of heroism. Duringthe1940s,GiuseppePardoRoques was the leader ofthe Jewish community in

Pisa, Italy. Hewaswidelyrespected as a spiritualguide—but he was alsoimpaired by cripplinganxiety,inparticularbyanoverwhelming phobia ofanimals. Hoping toconquer his anxiety, hetriedeverything:sedatives,“tonics” (neurophosphatesmeant to strengthen thenervous system),psychoanalysiswithoneof

Freud’s protégés, and—inanendeavorIcanrelateto—reading everything hecould get his hands on,fromHippocratestoFreud,about the theory andscience of phobias.Nothing worked; hisphobia dominated his life.Hewasunable to travel—was barely able to leavehis house—because of theirrational fear that he

would be set upon bydogs.Whenhedidmusterthe courage to walk thestreets, he would swing acanewildlyaroundhimselfatalltimestofendofftheanimals he feared mightattack. After neighborsacquired a pet dog, hecontrived a reason to getthem evicted because hecouldn’t bear to have ananimal so close by. He

spent hours every daycompleting elaborateritualsmeanttoassurehimthere were no animals inhis house. (Today, hewould be diagnosed withOCD.)Roques recognized the

irrationalityofhisfearbutwas powerless toovercome it. “Its intensityis just as great as itsabsurdity,”heoncesaid.“I

am lost. My heart beatsfast; my face no doubtchanges expression. I amno longer myself. Thepanic increases, and thefear of the fear increasesthe fear. A crescendo ofsuffering engulfs me. Ibelieve I will not be ableto hold my own. I searchfor help; I don’t knowwhere to find it. I amashamed to ask for help,

and yet I am afraid thefearwillmakemedie.Idodie, like a coward, athousanddeaths.”Silvano Arieti, a young

man who lived in thecommunity,wasfascinatedby Roques. How was it,Arietiaskedhimself,thataman as brilliant and wiseas Roques could allow hislifetobecircumscribedbyso irrational a fear?

Roqueswasafraidtotravel—hehadneverleftPisainall his sixty years—andthere were days when hisanxietywassobadthathecouldn’t even leave hisbedroom. But—and here’swhatwassofascinatingtoArieti—Roques showedhimself in other ways “tobeanutterlyfearlessman,courageously prepared todefend the

underprivileged, theunderdog,thedistressedinany way.… His almostconstant fear wasaccompanied by aconstantly availablecourage.”Hecouldhandle“real” fears and, in fact,would bravely help othersbesetbythem.Buthisownphobias, “in their fullytragic intensity,” he washelpless to do anything

about. Was there a link,Arieti wondered, betweenRoques’s moral strengthandhismentalillness?Many years later, after

he hadmoved to Americaand become one of theworld’s foremost scholarson mental illness, Arietiwouldpublishabook,TheParnas: A Scene from theHolocaust(1979),inwhichhe recounted what

happened inPisaafter theGermans occupied part ofItaly. Throughout 1943and 1944, as first theItalian Fascists and thenthe Nazis terrorized Pisa’sJewish community, mostJews fled. But Roques,prevented by his anxietyfrom traveling, stayed inPisa.“Theideaofgoingfaraway from home, toanother city, or to the

country, increases myanxiety to the point ofpanic,” Roques told sixfriends who chose forvarious reasons to remainin the city with him. “Iknow that these fears areabsurd to the point ofbeing ridiculous, but it isuseless to tellmyself so. Icannot overcome them.”Whenhisfollowerstriedtoattributehiswillingnessto

brave bombs andNazis tocourage or spiritual grace,Roques demurred. Hisillness, he said, “hascaused such a narrowingofmy life,not tomentiongossip and ridicule, andhas shadowed my wholeexistence.Ilive,trembling,with a totally irrationalfear of animals, especiallyofdogs. I alsohavea fearof the fear itself.… Had I

not felt this sick fearconstantly, Iwouldnotbehere;Iwouldbefaraway.Whatyoucallaspecialgiftisillness.”Butthefactthathis fear of dogs wasgreater than his fear ofbombs and Nazis madehimappearbrave.Earlyon themorningofAugust 1, 1944, theNazisarrived at Roques’s homeand demanded that he

surrender the guests whowerestayingwithhim.Herefused.“Aren’t you afraid ofdying?” the Nazisdemanded. “We will killyou,youfilthyJew.”“I am not afraid,” hetoldthem.And according to thosewho survived and werelaterinterviewedbyArieti,Roquesmanifestlywasnot

afraid, even though heknewtheNaziswereaboutto murder him. As realdanger approached, heappeared to be free offear.zGiuseppe Pardo Roques

was not the only Pisanimprisoned by his anxietyduring thewar.When thebombs started falling,reducing parts of the citytorubble,mostpeopleleft.

But Pietro, a young manwho lived not far fromRoques,couldnotgomorethan a block from hishouse; his agoraphobiawouldnotpermitit.Sohestayedhome.Pietrowouldsooner have had a bombdropped on his head thanendure the terror thatseized him when hewalked too far from hishouse.“Thefearcausedby

the neurosis was strongerthan the fear of thedangersofthewar,”Arietiobserves.Pietro survived the war

—andendedupdecoratedas a hero for his courage.After each bombing, hewould run out into theruins(solongastheywerewithin a block of hishouse) and free peopletrapped in them. In this

way, he saved severallives.Onlybecausehewasconstrained by his phobiawas he available to helpthe bombing victims. “Hisillnessmadehimbecomeahero,”Arietiwrites.To someonewho suffers

fromanxiety,thestoriesofRoques and Pietro, and ofBill Russell and FloydPatterson, hold obviousappeal;intheiranxietylies

not just redemption but asource of moral heroismand even, perhaps, astrangesortofcourage.

* Together, the alcohol and thebenzodiazepines slow the firingof neurons in my amygdala,increase transmission ofdopamine and gamma-aminobutyric acid, boostproduction of beta-endorphins in

my hypothalamus, and decreasetransmissionofacetylcholine.

† Of course, to opiumWilberforcelikely owed many other things,too, among them his horribledepressionandahostofphysicalproblems. After initially beingprescribed the drug for boweltroubles, he became addicted,taking it every day for forty-fiveyearsstraight.

‡ Actually, Olivier seems not tohave resorted to drugs. “There

was no other treatment than thewell-worn practice of wearing it—the terror—out,” he wrote inhisautobiography,“anditwasinthat determined spirit that I gotonwiththejob.”Buthedidquitthestage for fiveyears toescapehisanxiety.

§Foratime,WilliamstookPaxilforhis anxiety, and he brieflybecame a pitchman forSmithKline Beechman—thoughhe later told The Miami Herald

thatmarijuana“worked10timesbetterformethanPaxil.”

‖ Early in his career, SigmundFreud took cocaine to medicatehissocialanxietybeforesalonsatthehomeofoneofhismentors.

a The term “social phobia” firstappeared in 1903, when PierreJanet, an influential Frenchpsychiatrist who was acontemporaryandrivalofFreud,published a taxonomy of mentalillnesses that classified

erythrophobia among what hecalled phobies sociales or phobiesdelasociété.

b Ifnothingelse, thisdemonstratesthe complex ways in whichculture and medicine interact:what’snormal,evenvalorized,inone culture is consideredpathologicalinanother.

c Liebowitz also developed whatbecame the standardpsychological rating scale formeasuring a patient’s degree of

socialanxiety.

d Paxil had earlier been approvedfor the treatment of depression,obsessive-compulsive disorder,andgeneralizedanxietydisorder.

eLane’sbookisrepresentativeofasubstantial and ever-growingliterature that accuses thepharmaceutical-industrialcomplex of creating new diseasecategories for profit. I will havemoretosayaboutthisinpart3.

fResearchhasshownthatbeingtheobject of another’s direct gaze ishighly emotionally andphysiologically arousing. One ofthe surest ways to cause theneurons in the amygdala of ahuman test subject to fire issimply to have someone stare atthe subject. Many studies havedemonstratedthattheamygdalaeof those diagnosed with socialanxiety disorder tend to beconsistentlymore reactive to the

humangazethanthoseofhealthycontrolsubjects.

g Peter, I can only assume, felt nosuch anxiety. He went on tobecome a member of PresidentBarack Obama’s first-termcabinet.

h It didn’t help that the choirdirector was a strange andtyrannical man who lived withhis parents and had a horrificstutter. He’d start screaming atyou during choir practice and

would get stuck on a word, hisfacecontortedintoaparoxysmofanger and frustration, and youwouldhavetowaitmanysecondsfor whatever expletive he wastrying to direct at you to finallyburstout.

i On a number of occasions, I sawother therapists from the centerputting their patients throughsimilar exposures at the samestore,forcingthemtoaskstrangequestionsortomakeobviousand

embarrassingmistakes.The storeemployees must have wonderedwhy they had so many weirdinteractions with apparentlyderangedcustomerseveryday.

j Ned’s case is drawn from JohnMarshall’sbook,SocialPhobia.

k Some social phobics find evenpositive attention to be aversive.Think of the young child whoburstsintotearswhenguestssing“Happy Birthday” to her at aparty—or of Elfriede Jelinek

afraidtopickupherNobelPrize.Social attention—even positive,supportive attention—activatesthe neurocircuitry of fear. Thismakessensefromanevolutionaryperspective. Calling positiveattention to yourself can incitejealousy or generate newrivalries.

l The phobic response gets deeplyconsolidatedintheneuronsoftheamygdalaandthehippocampus—whichisinpartwhatmakesitso

hardtostampoutphobias.Inthisway, anxiety can be wretchedlyself-reinforcing: stress activatesthe amygdala, which increasesanxiety; increased anxietystimulates the HPA axis, whichmakes the amygdala twitchierstill—and all of this neuralactivity deepens the associationof anxiety with the phobicstimulus, whether that’s socialinteraction or a turbulent planeflight. In short, being anxious

conditions you to be moreanxiousinthefuture.

mInterestingly,recentstudieshavefound that the happiest-seemingand least stressed monkeys arewhat we might call the betamales—those monkeys near thetopofthehierarchy,whotendtobeeasygoingandsociallyskillful.Beingthehighest-rankingmaleisa lot healthier and less stressfulthan being the lowest-rankingmale—but being a high-ranking

male who is not the highest-ranking male is even morehealthyandlessstressful,becauseyou’re not always having toworryaboutthepalacecoupthatthreatenstotoppleyou.

n All drugs of abuse elevatedopamine levels in the basalganglia—an area of the brainwheredopamineislowinsociallyanxious patients. A chronicdopamine deficit may helpaccount for why social phobics

are more likely than others tostrugglewithaddiction.

oAlthoughAsperger’s patients andsocial phobics in some wayssuffer from a similar problem—adifficulty in managing socialinteractionsthatputsoffothers—theyarriveatitfrommoreorlessopposite directions: whereas theAsperger’s patient is no good atimagining what’s in otherpeople’sminds, thesocialphobicistoogoodatit.

pIwilldiscusstherelationbetweengenes and anxiety in greaterdepthinchapter9.

q One of the hallmarks ofmodernity is an abidinguncertaintyabout status.Hunter-gatherer societies tended not tobe very socially stratified; formost of human history, peoplelived in fairly egalitariangroups.That changed during the MiddleAges.Fromthetwelfthcenturyorso all the way through the

AmericanRevolution,societywashighlystratified—butalsolargelyfixed: people didn’t movebetween feudal castes. Modernsociety,incontrast,isbothhighlystratified(there’sahighdegreeofincome inequality in manycountries) and highly fluid. Thenotionthatanyonecan,withluckand pluck, rise from poverty tothe middle class, or from themiddle class to great wealth, isintegral to our idea of success.

But not all mobility is upward.Unlike in a society with morefixed socioeconomic strata, thereis always the fear of falling—afear that is heightened ineconomic times like these. ThemanyforcesbearingdownontheAmerican worker—the creativedestruction of free-marketcapitalism; thedisruptions to thelaborforcecausedbytechnology;the changing and uncertainrelations between the sexes and

the accompanying confusionabout gender roles—combine toproduce constant uncertainty.People naturally worry: Am Ibeing overtaken by other peoplewithmorerelevantjobskills?WillIlose my job and fall out of themiddle class? Some have arguedthat this chronic uncertainty isphysically rewiring our brains tobemoreanxious.

r Even, and perhaps especially,psychotherapistsarenotimmune.

Because they feel patients andpeers look to them to be incontrol of their emotions, thepressure psychotherapists put onthemselvesnottoappearanxiousoragitatedcanbegreat—andcanperversely make them feel moreanxiousandoutofcontrol.Ihaveon my shelf several books bytherapistswhohaveat times felthandicapped and humiliated bytheir own anxiety. The AnxietyExpert: A Psychiatrist’s Story of

Panic (2004) was written byMarjorie Raskin, a psychiatristspecializing in anxiety who wastorturedbypanicattacksbroughton by public speaking. Shewentto great lengths to hide heranxiety and, like me, medicatedherself heavily withbenzodiazepines. Painfully Shy:How to Overcome Social AnxietyandReclaimyourLife (2001)wascowritten by a psychologist,BarbaraMarkway,who concedes

that she herself has not, in fact,ever fully “overcome her socialanxietyorreclaimedherlife.”

sTherehavebeeneliteathletesforwhomthishasbeenthecase,too.Reno Bertoia, to name just one,was a young third baseman forthe Detroit Tigers who onceseemedtohaveabrightfutureinthe major leagues—until, in1957,hebecamesooverwhelmedby anxiety that, as the Tigers’trainerobserved,he“couldn’thit

and sometimes bobbled fieldingplays that should have beeneasy.” Themore nervous Bertoiagot, the worse he played; theworse he played, the morenervoushegot—aclassic viciouscycle of ever-increasing anxietyandever-decreasingperformance.Soon,hisplayhadsodeterioratedthat Tigers management was onthe verge of dropping him fromthe team. Desperate andunhappy, Bertoia resorted to

taking Miltown, an early, pre-Valium tranquilizer. Thetransformation was astounding.Bertoia “stopped holding himselfin,” the trainer reported. “He’s adifferent man on the bench—talking and joking—and muchmore relaxed.” On the field,meanwhile,hestarted“poundingthe ball in tremendous fashion.”His batting average rose ahundredpoints.

t This diagnosis had been applied

informally since the FrenchRevolution to men who brokedown during combat, but it wasonly in 1871, when a physiciannamed Jacob Mendes Da Costawrote up a case study on Henryfor The American Journal of theMedical Sciences, that theconditionwas formally inscribedin the scientific literature assoldier’s heart or irritable heartor Da Costa’s syndrome.Historians of psychiatry often

identifythisarticleasthefirst inthemedical literaturetodescribethe conditions we would todaycall panic disorder and post-traumaticstressdisorder.

uThe relationship between lack ofcontrol and anxiety has beendemonstrated many times overthe years in noncombatsituations, too. Researchers haveproduced ulcers in mice simplybydeprivingthemofcontrolovertheir environment, and a raft of

studies have demonstrated thatpeople in jobs where they don’tperceivethemselvestohavealotof control are much moresusceptible todeveloping clinicalanxietyanddepression,aswellasstress-related medical conditionslikeulcersanddiabetes.

vPTSDis thesuccessor tosoldier’sheart, shell shock, battle fatigue,and war neurosis, among otherdiagnoses.

w Researchers are currently

investigating whetheradministering NPY via a nasalspray could help block thedevelopment of post-traumaticstressdisorder.

x Of course, when a nervousstomachimpairsperformance,thecomplexionchangesdramatically.Consider the difference betweenBill Russell and DonovanMcNabb, the quarterback for thePhiladelphia Eagles during the2005 Super Bowl. Like Russell,

McNabb was an elite athlete. Asix-time Pro Bowler and theholder of almost all the Eagles’passingrecords,McNabbwasoneofthemostsuccessfulcollegeandpro quarterbacks of hisgeneration. Yet despite manyplayoff victories,McNabb,unlikeRussell, never won achampionship—andeversincehisteam lost that 2005 Super Bowlgame,hehasbeendoggedbytheclaims of several teammates

(which McNabb denies) that hewas vomiting in the huddle andcouldn’t call plays. (The debateoverwhetherMcNabbdidordidnot vomit in the huddle stillcontinues eight years after thegame, and has been called “oneof the great mysteries in thehistory of sport.”) Theimplication is that McNabb, forall his athletic talent, wasoverwhelmed by the pressure ofthe occasion and succumbed to

nerves, that he lacked theleadership qualities, thetoughness—the literal intestinalfortitude—tokeephisstomachincheck and lead the Eagles tovictory. McNabb has never beenseen the same way since.(Augmenting his reputation as achoker:McNabb’s stats incrucialplayoff games were markedlyworse than his stats in ordinaryregular-seasongames.)

y “When did you first think you

were a coward?” Talese askedhim. “It was after the firstIngemar fight,” Patterson said.“It’s indefeat thatamanrevealshimself. In defeat, I can’t facepeople. I haven’t the strength tosaytopeople, ‘Ididmybest,I’msorry,’andwhatnot.”

z In his book, Arieti elaborates atheory about why this shouldhavebeenthecase.Hisviewwasthat Roques’s phobia of anddisgust at animals was a

displacementofhisdisgustattheevil inherentinman.Asayoungboy,Roqueshadbeenhappyandoptimistic.Butduringhis studiesas an adolescent, he discoveredthe facts of the Crusades, theInquisition,andthemyriadotherhorrorsthatmanhasvisiteduponman across history. He couldn’tbear this. To preserve a lovingview of humankind, and a viewof theworld as a friendly place,Arietitheorizes,Roquesprojected

onto animals the evil that is inman, preferring to fear animalsrather than give up his view ofmankind as essentially good.When Roques was confrontedunavoidablywithevilintheformof the Nazis, his animal phobiadisappeared. This, Arieti argues,gives his phobic anxiety analmost spiritual quality, since itpermitted him to displacerevulsion and anxiety ontoinsentientcreatures,allowinghim

toretainloveforhumankind.

“When the sensitive youngsterhas made these unpleasantrealizations [about the evil inmanandthedangerandhardshipof existence],” Arieti writes, “hehasdifficultiesinfacinglife.Howcanhe trust,howcanhe loveorretain a loving attitude towardsfellow human beings? He mightthen become suspicious andparanoid; he might become adetached person unable to love.

But this is not the casewith thephobic. The phobic is a personwhoretainshisabilitytolove.Asa matter of fact, in my longpsychiatric career I have neverseen a phobic person who wasnot a loving person.” We areborn,itseems,intoaRousseauianstate of innocence, but if weaccurately observe life andhuman nature, we must adopt aHobbesian defensive crouchagainst life’s depredations.

PhobiassublimateourHobbesianhorror into neurotic andirrational fears, Arieti argues,allowing us to preserve a moreinnocent and loving stancetowardtheworld.

PARTIII

Drugs

CHAPTER5

“ASackofEnzymes”

Fromtimeimmemorial,[drugs] have beenmaking possible somedegree of self-transcendence and a

temporaryreleasefromtension.—ALDOUSHUXLEY,INA

MAY9,1957,PRESENTATIONTOTHENEWYORKACADEMYOF

SCIENCE

Wine drunk with anequalquantityofwaterputs awayanxiety andterror.

—HIPPOCRATES,APHORISMS(FOURTHCENTURYB.C.)

In anticipation of thereleaseofmyfirstbook,inthe spring of 2004, mypublisher arranged amodest publicity tour thatentailednationaltelevisionand radio appearances, as

wellasbookstore readingsandpubliclecturesaroundthe country. This shouldhave been a delightfulprospect—the chance topromote my book, totravel on someone else’snickel, to connect withreaders, to achieve a kindof temporary, two-bitcelebrity. But I canscarcely convey whatpowerful dread this book

tourconjuredinme.In desperation, I sought

help from multiplesources. I first went to aprominent Harvardpsychopharmacologistwhohadbeenrecommendedbymyprincipalpsychiatristayearearlier.“Youhaveananxiety disorder,” thepsychopharmacologist hadtold me after taking mycase history at our initial

consultation. “Fortunately,thisishighlytreatable.Wejust need to get youproperly medicated.”When I gave him mystandard objections toreliance on medication(worry about side effects,concerns about drugdependency, discomfortwith the idea of takingpills that might affect mymind and change who I

am), he resorted to theclichéd—but nonethelesspotent—diabetesargument,whichgoes likethis: “Your anxiety has abiological, physiological,and genetic basis; it is amedical illness, just likediabetes is. If you were adiabetic, you wouldn’thave such qualms abouttakinginsulin,wouldyou?Andyouwouldn’tseeyour

diabetesasamoralfailing,would you?” I’d hadversions of this discussionwith various psychiatristsmanytimesovertheyears.I would try to resistwhatever the latest drugwas, feeling that thisresistance was somehownoble or moral, thatreliance on medicationevinced weakness ofcharacter, thatmyanxiety

was an integral andworthwhile component ofwho I am, and that therewas redemption insuffering—until,inevitably, my anxietywould become so acutethat Iwould bewilling totryanything,includingthenew medication. So, asusual,Icapitulated,andasthe book tour loomed, Iresumed a course of

benzodiazepines (Xanaxduring the day, Klonopinatnight)andincreasedmydosageofCelexa,theSSRIantidepressant I wasalreadytaking.Butevendruggedtothe

gills,Iremainedfilledwithdreadabouttheimpendingbook tour, so I went alsoto a young but highlyregarded Stanford-trainedpsychologist who

specialized in cognitivebehavioral therapy, orCBT.“Firstthingwe’vegotto do,” she said in one ofmyearlysessionswithher,“is to get you off thesedrugs.” A few sessionslater, she offered to takemy Xanax from me andlock it in a drawer in herdesk. She opened thedrawer to show me thebottles deposited there by

someofherotherpatients,holding one up andshaking it for effect. Thedrugs, she said, were acrutch that prevented mefrom truly experiencingand thereby confrontingmy anxiety; if I didn’texpose myself to the rawexperience of anxiety, Iwould never learn that Icould cope with it on myown.

She was right, I knew.Exposure therapy is basedon fully experiencingyouranxiety, which is hard todo if you’re takingantianxiety medications.But with the book tourlooming,myfearwas thatImightnot,infact,beabletocopewithit.I went back to theHarvardpsychopharmacologist

(let’scallhimDr.Harvard)and described the courseof action the Stanfordpsychologist (let’s call herDr. Stanford) hadproposed. “It’s your call,”he said. “You could trygiving up the medication.Butyouranxiety isclearlyso deeply rooted in yourbiology that even mildstress provokes it. Onlymedication can control

your biological reaction.And it may well be thatyour anxiety is so acutethattheonlywayyou’llbeable to get to the pointwhere any kind ofbehavioral therapy canbegin to be effective is bytaking the edge off yourphysical symptoms withdrugs.”“What if I get addicted

to Xanax and have to be

onitallmylife?” Iasked.Benzodiazepines arenotorious for inducingdependency. Withdrawingtoo suddenly from themcan produce horrific sideeffects.“Sowhatifyoudo?”he

said. “I have a patientcoming in this afternoonwho’s been taking it fortwentyyears. She couldn’tlivewithoutit.”

Atmynext sessionwithDr. Stanford, I told her Iwas afraid to give up myXanax and related whatDr. Harvard had said tome.Shelookedbetrayed.Ithoughtforamomentthatshemightcry.Afterthat,Istopped telling her aboutmy visits to Dr. Harvard.My continuedconsultationswithhimfeltillicit.

Dr. Stanford was morelikable,andmorepleasantto talk to, than Dr.Harvard; she tried tounderstand what causedmyanxietyandseemedtocare about me as anindividual personality. Dr.Harvard, on the otherhand,seemedtoseemeasa type—ananxietypatient—tobetreatedwithaone-size-fits-allsolution:drugs.

One day I read in thenewspaper that he wastreatingadepressedgorillaat the local zoo. Dr.Harvard’s treatment ofchoice for the gorilla inquestion?Celexa,thesameSSRI he was prescribingforme.I can’t say for certain

whether the drug workedforthegorilla.Reportedly,itdid.Butcouldtherebea

more potentdemonstration that Dr.Harvard’s approach totreatment was resolutelybiological? For him, thecontent of any psychicdistress—and certainly themeaning of it—matteredless than the fact of it:suchdistress,whetherinahuman or some otherprimate, was a medical-biologicalmalfunctionthat

couldbefixedwithdrugs.Whattodo?Dr.Harvardwas tellingme that I, likethe gorilla, had amedicalproblem in need ofpharmaceuticalintervention. Dr. Stanfordwas telling me that myproblem was notprincipally biological butrathercognitive: if Icouldsimply correctdysfunctions in how I

thought (through force ofwill and cognitiveretraining and directexposure to my greatestfears), then my anxietywouldbereduced.Butthedrugs I was on, Dr.Stanford said, wereimpeding my ability toaddress thosedysfunctionsinaneffectiveway.*I kept trying to give up

myKlonopinandXanaxin

order to do propercognitive retraining, and Iwould sometimes evensucceed at this in smallways—only to beoverwhelmedwithanxietyagain and resort tofumbling miserablythroughmypocketsfortheXanax.AsmuchasIwouldhave liked to have curedmyself through fixing mythinking, or achieving

spiritual peace, or simplylearning tocope, I seemedalways to be ending uplike the depressed gorilla,in need of artificialadjustments to myneurotransmitters to fixmyanxious,brokenbrain.

Tranquilizers, byattenuating thedisruptive influence ofanxiety on the mind,

open the way to abetter and morecoordinated use of theexisting gifts. By doingthis,theyareaddingtohappiness, humanachievement, and thedignityofman.—FRANKBERGER,“ANXIETYANDTHEDISCOVERYOF

TRANQUILIZERS,”IN

DiscoveriesinBiologicalPsychiatry

(1970)

To what extent wouldWestern culture bealtered by widespreaduse of tranquilizers?Would Yankeeinitiative disappear? Isthechemicaldeadeningofanxietyharmful?

—STANLEYYOLLES,DIRECTOROFTHE

NATIONALINSTITUTEOFMENTALHEALTH,IN

TESTIMONYGIVENTOTHEU.S.SENATESELECTCOMMITTEEONSMALLBUSINESS,MAY1967

Sigmund Freud, thefather of psychoanalysis,relied heavily on drugs inmanaging his anxiety. Six

of his earliest scientificpapers were on thebenefits of cocaine, whichhe used regularly for atleastadecadebeginninginthe 1880s. “In my lastserious depression I tookcocaine again,” he wrotetohiswifein1884,“andasmalldoseliftedmetotheheights in a wonderfulfashion. I am just nowcollectingtheliteraturefor

a song of praise to thismagical substance.” Hebelieved his research onthe drug’s medicinalproperties would makehim famous. Deeming thedrug to be no moreaddictive than coffee, heprescribed it, to himselfand to others, as atreatment for everythingfrom nervous tension andmelancholy to indigestion

and morphine addiction.Freud called cocaine a“magicdrug”:“I takeverysmall doses of it regularlyagainst depression andagainst indigestion, andwith the most brilliantsuccess.”Healsotookittoalleviatehis social anxietybefore the evening salonshe attended at the Parishome of his mentor Jean-Martin Charcot.† Only

afterheprescribedcocainetoaclosefriendwhowenton to become fatallyaddicted did Freud’senthusiasm for the drugwane.Butby thenFreud’sown experience withcocaine had solidified hisconviction that somemental illnesses have aphysicalbasisinthebrain.It is an irony of medicalhistory that even as

Freud’s later work wouldmake him the progenitorofmodern psychodynamicpsychotherapy, which isgenerally premised on theidea that mental illnessarises from unconsciouspsychologicalconflicts,hispapers on cocaine makehim one of the fathers ofbiological psychiatry,which is governed by thenotionthatmentaldistress

is partly caused by aphysical or chemicalmalfunction that can betreatedwithdrugs.Much of the history of

modernpsychopharmacology hasthesameadhocqualityasFreud’s experimentationwithcocaine.Everyoneofthe most commerciallysignificant classes ofantianxiety and

antidepressantdrugsofthelast sixty years wasdiscovered by accident orwas originally developedfor something completelyunrelated to anxiety ordepression: to treattuberculosis, surgicalshock, allergies; to use asan insecticide, a penicillinpreservative, an industrialdye, a disinfectant, rocketfuel.

Yet despite itshaphazardness, the recenthistory ofpsychopharmacology hasshaped our modernunderstanding of mentalillness. Recall that neither“anxiety” nor“depression”—two termsthat today have becomepart of both the medicaland the popular lexicon—existed as clinical

categories half a centuryago. Before the 1920s, noone had ever beendiagnosedwithdepression;before the 1950s, hardlyanyone was diagnosedwith straightforwardanxiety.So what changed? Oneanswer is thatpharmaceutical companiesin effect created thesecategories.What began as

targets for marketingcampaigns eventuallybecamereifiedasdiseases.BythisIdonotmeantosuggest that before the1950s people were not“anxious” or “depressed”in the senses weunderstand those wordstoday. Some people, somepercentage of the time,have always feltpathologically unhappy

and afraid. This was thecase for millennia beforethe terms “anxiety” and“depression” werepopularized to describeemotionalstatesorclinicaldisorders. (“The tears ofthe world are a constantquantity,” as SamuelBeckett put it.) But notuntilthemiddleofthelastcentury, when new drugsgeared toward mitigating

these emotional stateswere concocted, did thesestates get delimited as the“diseases” we understandthemtobetoday.Before 1906, when thefledgling Food and DrugAdministration startedrequiring drugmakers tolist their products’ingredients, consumersdidn’t realize that intaking some of the most

popular antianxietyremedies of the time—such as Neurosine or Dr.Miles’sNervine(advertisedas “the scientific remedyfor nervous disorders”) orWheller’s Nerve Vitalizersor Rexall’s AmericanitisElixir—theywereingestingalcohol or marijuana oropium.‡ In 1897, theGerman drug companyBayer began marketing

diacetylmorphine, acompound that had beenwidely used on thebattlefields of theAmerican Civil War andthe Franco-Prussian War,as a painkiller and coughsuppressant. This newmedication—under thetrade name Heroin—wasavailable in Americanpharmacies without aprescription until 1914.§

The 1899 edition of TheMerckManual,thenasnowa respected compendiumof the most up-to-datemedical information,recommended opium as astandard treatment foranxiety.The serene confidencewith which The MerckManual—as well as thephysicians andapothecariesof the time—

glibly dispensedrecommendations fordrugswenowknow tobeaddictive, unhealthy, oruseless raises the questionof whether we shouldplace much trust in thesimilarlysereneconfidenceofthephysiciansanddrugmanuals of today. Yes,today’s researchers andclinicians are armed withdata from controlled

studies and findings fromneuroimaging and bloodassays, and they arebuttressed—or held back,depending on yourperspective—by a morecautious FDA thatdemands years’ worth ofanimal testingandclinicaltrialsbeforeadrugcanbeapproved for sale. But ahundred years from now,medical historians may

onceagainbemarvelingatthe addictive, toxic, oruseless substances weconsume in such greatquantitiestoday.For the first half of thetwentieth century,barbiturateswerethemostpopular remedy forstrained nerves. Originallysynthesized in 1864 by aGerman chemist whocombined condensed urea

(found in animal waste)with diethyl malonate(which derives from theacid in apples), barbituricacid seemed, at first, tohave no productive use.But in 1903, whenresearchers at Bayer gavebarbituricacidtodogs,thedogs fell asleep. Withinmonths, Bayer wasmarketing barbital, thefirst commercially

available barbiturate, toconsumers. (Bayer namedthe drug Veronal becauseone of its scientistsbelieved Verona, Italy, tobe the most peaceful cityon earth.) In 1911, thecompany released alonger-acting barbiturate,phenobarbital, under thetrade name Luminal,which would go on tobecome the most popular

drug in the category. Bythe 1930s, barbiturateshad almost completelydisplaced their latenineteenth-centurypredecessors—chloralhydrate and bromides, aswell as opium—as thetreatment of choice for“nervetroubles.”‖As early as 1906, somany Americans weretaking, and sometimes

overdosing on, Veronalthat The New York Timeseditorialized against theoverprescription of such“quick-curenostrums,”butto little effect: in the1930s, The Merck Manualwas still recommendingVeronal for the treatmentof “extreme nervousness,neurasthenia,hypochondria,melancholia,” and other

“conditions of anxiety.”Veronal and Luminal—advertised as “aspirin forthe mind”—dominatedwhat would today becalled the anxietymedication market fordecades. By 1947, therewere thirty differentbarbiturates being soldunder separate tradenames in the UnitedStates; the three most

popular were Amytal(amobarbital), Nembutal(pentobarbital), andSeconal (secobarbital).Since “anxiety” and“depression” didn’tofficially exist yet, thebarbiturates tended to beprescribedfor“nerves”(or“nerve troubles”),“tension,”andinsomnia.Butthebarbiturateshad

two big drawbacks: they

werehighlyaddictive,andaccidental overdoses werecommon and often lethal.In 1950, at least athousandAmericansfatallyoverdosedonbarbiturates.(My great-grandmotherand Marilyn Monroe,amongmanyothers,wouldgo on to do so in the1960s.) In 1951, The NewYork Times calledbarbiturates “more of a

menace to society thanheroin or morphine” anddeclared that “the matronwhoregardsapinkpillasmuch of a bedtimenecessity as brushing herteeth, the tense businessman who gulps a whitecapsule to ease his nervesbefore an importantconference, the collegestudent who swallows ayellow‘goofball’tobreeze

through an examination,and theactorwho takesa‘blue angel’ to bolster hisself-confidence are awarethat excessive use ofbarbiturates is ‘not goodfor the system,’ but areignorant of the extent ofthehazard.”You would think that

suchheavyconsumptionofbarbiturates would havemade drug companies

keen to develop new andbetternostrums.ButwhenFrank Berger, a researchscientist at the WallaceLaboratories subsidiary ofCarter Products, tried tointerest companyexecutives in a newantianxiety medication hehadsynthesizedinthelate1940s, they showed nointerest. For one thing,they argued, therapy for

anxiety was supposed tofocus on psychologicalissues or unresolvedpersonal problems, not onbiology or chemistry—adistinction that from thevantage point of modernbiological psychiatryseems quaint. Besides,psychoactive drugs layoutside Carter’s usualcommercialdomain,whichconsistedofsuchthingsas

laxatives (Carter’s LittleLiver Pills), deodorant(Arrid), and depilatorycream(Nair).Berger had stumbled on

the antianxiety propertiesof this new substanceentirely by accident. Bornin what is now the CzechRepublic in 1913, Bergerhad, after earning hismedical degree at theUniversity of Prague,

conducted immunologyresearch that establishedhim as a promisingscientist. But when Hitlerannexed Austria andseemed poised to claimCzechoslovakia, Berger,who was Jewish, escapedtoLondon.Unable to find workthere, Berger and hiswifebecamehomeless,sleepingon park benches and

eating at soup kitchens.Eventually, Berger got ajobasadoctorinarefugeecamp, where he learnedEnglish, and then movedon to a job as anantibiotics researcher atthe Public HealthLaboratorynearLeeds.By 1941, penicillin hadbeen demonstrated to bean effective treatment forbacterial infections. But

manufacturing andpreserving penicillin inquantities large enough tobe useful in fightinginfections among Alliedsoldiers proved vexing.“The mold is astemperamentalasanoperasinger,” lamented onepharmaceutical executive.So Berger, along withhundreds of otherscientists, went to work

trying to find betterextractionandpurificationtechniques for therevolutionary antibiotic.He was particularlysuccessful in developing amethod for preserving themold long enough todistribute it more widely.After his research waspublished in prestigiousscientific journals, aBritish drug company

offered the once-homelesschemist a high-rankingposition.One of the penicillin

preservativesBergertestedwas a compound calledmephenesin,whichhehadsynthesizedbymodifyingacommercially availabledisinfectant. When heinjected mice withmephenesin to test itstoxicity, Berger observed

somethinghe’dneverseenbefore: “The compoundhad a quieting effect onthe demeanor of theanimals.”Berger had, quite byaccident, discovered thefirst of a revolutionarynew class of drugs. Whenmephenesin was found tohave a similar sedatingeffect on humans, theSquibb Corporation,

recognizing a commercialopportunity, begandistributingmephenesinasadrugtoinducerelaxationbeforesurgery.Soldunderthe trade name Tolserol,mephenesin had by 1949become one of Squibb’smostprescribeddrugs.But mephenesin wasn’tvery potent in pill form,and its effectswere short-lived. Berger resolved to

develop a more powerfulversion. In the summer of1949,hetookajobasthepresident and medicaldirector of Carter’sWallaceLabssubsidiaryinNew Brunswick, NewJersey. There, Berger andhis team set to worksynthesizing and testingcompounds that mightprove more potent thanmephenesin. Eventually,

they identified a dozen(out of the roughly fivehundred they synthesized)that seemed promising;aftermoreexperimentsonanimals, they narrowedthe list down to four andthen to one, calledmeprobamate, which theypatented in July 1950.Berger’s team found thatmeprobamate relaxedmice. The effect on

monkeys was even morevivid. “We had abouttwenty Rhesus and Javamonkeys,” Berger wouldlater tell the medicalhistorian Andrea Tone.“They’re vicious, andyou’ve got to wear thickgloves and a face guardwhen you handle them.”But after they wereinjected withmeprobamate, they

became “very nicemonkeys—friendly andalert.” Further testingrevealed meprobamate tobe longer lasting thanmephenesin and less toxicthanbarbiturates.Meanwhile, two new

papers in top medicaljournals were providingthe first reports of thetherapeutic effects ofmephenesin—which,

remember,waslesspotentthanmeprobamate.Oneofthe studies, conducted bydoctorsattheUniversityofOregon, found that whenmephenesin was given to124 patients who hadsought treatment fromtheir physicians for“anxiety tension states,”more than halfexperienced a significantreduction in anxiety—to

the point where theyresembled,inthewordsofthe researchers,“individuals who arepleasantlyandcomfortablyat ease.” Other reportsfrom mental hospitalsshowed similar results.Soon the first small-scalestudies of meprobamatewere finding the samething: the drugsignificantly reducedwhat

doctorsofthetimetendedtocall“tension.”These studies wereamongthefirsttomeasurein any kind of systematicway the effects of a drugon the mental states ofhuman beings. Today,when reports onrandomized controlledtrials of the efficacy ofvariouspsychotropicdrugsarepublishedby thescore

every month innewspapers and medicaljournals,thiskindofstudyseems routine. But atmidcenturythenotionthatpsychiatric drugs could bewidely and safelyprescribed—let alonescientifically measured—wasnovel.So novel, in fact, that

Carter executives didn’tbelievetherewasamarket

for such a drug. Theyretained a pollingcompany to ask twohundred primary carephysicians whether theywould be willing toprescribeapill thatwouldhelp patients with thestresses of day-to-day life—and a large majority ofthemsaid theywouldnot.Frustrated, Bergerpersisted on his own,

sendingmeprobamatepillsto two psychiatrists heknew, one in New Jerseyand one in Florida, fortesting. The New Jerseypsychiatrist reported backthat meprobamate hadhelped 78 percent of hispatients suffering fromwhatwewould today callanxiety disorders—theybecame more sociable,slept better, and in some

cases returned to workafter being housebound.Thepsychiatrist inFloridagave the drug to 187patientsandfoundthat95percent of those with“tension” improved orrecovered onmeprobamate.“When I first came inhere,Icouldn’tevenlistento the radio. I thought Iwas going crazy,” one of

the Florida psychiatrist’spatients reported after afew months onmeprobamate. “I now goto football games, shows,and even watch TV. Myhusband can’t get overhowrelaxedIam.”Berger showed theseresults—whichTheJournalof the American MedicalAssociation would publishin April 1955—to Henry

Hoyt, the president ofCarter Products, whofinally allowedmeprobamate to besubmitted for FDAapproval. The custom atCarter had been to namecompounds after localtowns, and someprobamate had beeninternally dubbedMilltown, after a smallhamlet about three miles

from Berger’s lab that aguidebookcalled“tranquillittle Milltown.” Sinceplace-names cannot betrademarked, Hoytdropped an l, and whenthepillcametomarket inMay 1955, meprobamatewascalledMiltown.In 1955, barbiturates

werestillthemostpopularantianxiety medication;they were marketed as

sedatives and haddominated the pharmacyshelves for severaldecades.Because theyhada proven sales record,Berger wanted to marketMiltownasasedative,too.But one night over dinnerin Manhattan, his friendNathanKline,theresearchdirector of Rockland StateHospital, advised againstthat.“Youareout of your

mind,” Kline said. “Theworld doesn’t need newsedatives.What the worldreally needs is atranquilizer. The worldneeds tranquility. Whydon’t you call this atranquilizer? You will sellten times more.” Out ofsuch contingencies—anunexpectedsideeffectofapenicillin preservative, astray remark at dinner—is

the history ofpsychopharmacologymade.Miltown was broughtquietly to market on May9, 1955. Carter Productssoldonly$7,500worthofthe drug in each of thefirst two months it wasavailable. But sales of thecompound—which wasadvertised as beingeffective for “anxiety,

tension, and mentalstress”—soon accelerated.In December, Americansbought$500,000worthofMiltown—and before longtheywerespendingtensofmillions of dollars a yearonMiltownprescriptions.In 1956, the drugbecame a culturalphenomenon. Movie starsand other celebrities sangthe praises of the new

tranquilizer. “If there’sanything this moviebusiness needs, it’s a littletranquility,”aLosAngelesnewspaper columnistdeclared.“Onceyou’rebigenough to be ‘somebody’infilmtownyou’vejustgottobeknee-deepintensionandmental and emotionalstress. The anxiety oftryingtomakeittothetopis replaced by the anxiety

of wondering if you’regoingtostaythere.So,bignamesandlittlealikehavebeen loading their trustypillboxes with this littlewonder tablet.” LucilleBall’s assistant kept asupply of Miltown on theset of I Love Lucy to helpthe actress calm downafter spats with herhusband, Desi Arnaz.TennesseeWilliams told a

magazine that he needed“Miltowns, liquor, [and]swimming” to get himthrough the stress ofwritingandproducingTheNight of the Iguana. Theactress Tallulah Bankheadjoked that she ought tohave been paying taxes inNew Jersey, home ofWallace Labs, because shewas consuming so muchMiltown. Jimmy Durante

and Jerry Lewis publiclypraised the drug ontelevised awards shows.ThecomedianMiltonBerletook to beginning themonologues on hisTuesday night televisionshow with “Hi, I’mMiltownBerle.”Withsomanyprominentchampions, Miltown’spopularity spreadnationally. Magazines

wrote about “happy pills”and“peaceofminddrugs”and “happiness byprescription.” Gala Dalí,the wife of the surrealistpainter SalvadorDalí,wassuchadevoteeofMiltownthat she convinced CarterProducts to commission a$100,000 Miltown artinstallation from herhusband.a Aldous Huxley—whom, based on the

drug-addled dystopia hepainted in Brave NewWorld, you might haveexpected to be a sternCassandra about suchthings—proselytized thatthe synthesis ofmeprobamate was “moreimportant,moregenuinelyrevolutionary, than therecent discoveries in thefieldofnuclearphysics.”Within eighteen months

of its introduction,Miltown had become themostprescribedand—withthe possible exception ofaspirin—the mostconsumed drug in thehistory of the world. Atleast 5 percent ofAmericans were taking it.“For the first time inhistory,” the neurologistRichardRestakwouldlaterobserve, “the mass

treatmentofanxietyinthegeneral communityseemedpossible.”Miltown contributed to

awholesaletransformationofthewaywethinkaboutanxiety.Before1955,therewas no such thing as atranquilizer—nomedication that wasdesigned to treat anxietyperse.(Thefirstuseoftheword “tranquilizer” in

English was by BenjaminRush, a physician andsignatory of theDeclaration ofIndependence, who usedthe term to describe achair he had invented torestrain psychoticpatients.)Butwithinafewyears, Americanpharmacies were full ofdozens of differenttranquilizers, and

companies were spendinghundreds of millions ofdollarstodevelopmore.The confidence ofpsychiatrists in the newdrugs could beoverweening. Testifyingbefore Congress in 1957,Frank Berger’s friendNathan Kline enthusedthat the advent ofpsychiatric drugsmay “beofmarkedlygreaterimport

in the history of mankindthan the atombomb sinceif these drugs provide thelong-awaited key whichwill unlock the mysteriesof the relationship ofman’s chemicalconstitution to hispsychological behaviorand provide effectivemeans of correctingpathological needs theremay no longer be any

necessity for turningthermonuclear energy todestructive purposes.”KlinetoldajournalistfromBusinessWeek thatmeprobamatewasgoodforboth economicproductivity (because itrestored “full efficiency tobusiness executives”) andartistic creativity (becauseit helped writers andartists break free of their

neuroses and overcome“mental blocks”). Thisutopian vision of betterliving through chemistrymayhavebeenoverblown,but itwasbroadly shared.By1960, some75percentof all doctors in Americawere prescribing Miltown.The treatment of anxietyhadbeguntomigratefromthe psychoanalyst’s couchto the family doctor’s

office. Soon attempts toresolve conflicts betweenthe id and the superegowere being displaced byefforts to better calibratethe neurochemistry of thebrain.

The deficiencies in ourdescription [of themind] would probablyvanish if we werealreadyinapositionto

replace thepsychological terms byphysiological orchemicalones.—SIGMUNDFREUD,BeyondthePleasurePrinciple(1920)

The insulin of thenervous.—FRENCHPSYCHIATRIST

JEANSIGWALD’S

CHARACTERIZATIONOFTHENEWLYDISCOVEREDDRUGCHLORPROMAZINE

(THORAZINE),1953

Meanwhile, a series ofunexpectedpharmacologicaldiscoveries inFrancewereto have medical andcultural consequences thatwereperhaps even furtherreachingthanMiltown’s.

In1952,HenriLaborit,asurgeon in Paris, decidedto experiment on some ofhis patients with acompound calledchlorpromazine.Chlorpromazine, like somany drugs that wouldfind their way into themodern psychotropicarsenal, had its origins inthe rapid growth of theGerman textile industry in

thelatenineteenthcentury—specifically in theindustrial dyes developedby chemical companiesstarting in the 1880s.bChlorpromazine came intobeing in 1950, whenFrench researcherssynthesized the newcompound fromphenothiazine, intendingto create amore powerfulantihistamine. But

chlorpromazine failed toimprove on existingantihistamines, so theyquicklyput itaside.WhenLaboritaskedthechemicalcompany Rhône-Poulencfor some chlorpromazine,he was hoping he wouldfind that its purportedqualities as anantihistamine would helpmitigate surgical shock byreducinginflammationand

suppressing the body’sautoimmune response tothe trauma of surgery. Itdid—but to Laborit’ssurprise, the drug alsosedated his patients,relaxing some of them tothepointwheretheywere,as he put it, “indifferent”toward the major surgicalprocedures they wereabouttoundergo.“Come look at this,”

Laborit reportedly said toone of the armypsychiatristsonthestaffofthe Val-de-Grâce militaryhospital, pointing out thatthe “tense, anxious,Mediterranean-typepatients” had becomecompletely calm, even inthefaceofmajorthreatstotheirhealth.Word got around thehospital, and one of

Laborit’s surgicalcolleagueswould soon tellhis brother-in-law, thepsychiatristPierreDeniker,about the effects of thisnew compound. Intrigued,Deniker administered thedrug to some of his mostpsychotic patients on theback wards of a Parisianmental hospital. Theresults were astounding:violently agitated patients

calmed down; the crazybecamesane.WhenoneofDeniker’s colleagues gaveit to a patient who hadbeen nonresponsive foryears, the man emergedfrom his stupor andwanted to leave thehospital and return to hiswork as a barber. Thedoctor asked him for ashave, which the patientcarefullygavehim,andso

thedoctordischargedhim.Not every case was asdramatic, but the calmingeffects of the drug werepowerful. Neighborsreported that the noiseemanating from theasylum had droppedsignificantly. Other small-scaleexperimentswiththedrug showed similarlypotent results. In 1953,Jean Sigwald, a

psychiatrist in Paris, gavechlorpromazine to eightpatients suffering from“melancholia withanxiety,”and fiveof themgotbetter.Chlorpromazinewas, Sigwald declared,“the insulin of thenervous.”Chlorpromazinecameto

North America when, oneSunday evening in thespring of 1953, Heinz

Edgar Lehmann, apsychiatrist at McGillUniversity in Montreal,read an article whileluxuriating in his bath.The article, which hadbeenleftinhisofficebyadrug company salesrepresentative,reportedonchlorpromazine’s effect onFrench psychotics. (“Thisstuff is so good that theliterature alone will

convince him,” thesalesman had toldLehmann’s secretary.)WhenLehmanngot out ofthe bath, he ordered ashipment of thecompound, and he used itto launch the first NorthAmerican trial ofchlorpromazine,administeringittoseventymentally ill patients atnearby Verdun Protestant

Hospital, where he servedas clinical director. Theresultsamazedhim:withinweeks, patients who hadbeen suffering fromschizophrenia, majordepression, and what wewould today call bipolardisorder, among otherpsychiatric ailments,seemed effectively cured.Many found themselvescompletely symptom-free;

someofthosewhodoctorshad thought would beconfined to asylums forlife left the hospital. Itwas,Lehmannwould latersay, “the most dramaticbreakthrough inpharmacology since theadvent of anesthesiamorethanacenturybefore.”Smith, Kline & French

Laboratories, an Americandrug company, licensed

chlorpromazine and in1954brought it tomarketwith the trade nameThorazine. Its arrivaltransformedmental healthcare. In1955, for the firsttime in a generation, thenumber of hospitalizedmentally ill in the UnitedStatesdeclined.cTogether,Thorazineand

Miltown reinforced aculturally ascendant new

idea—that mental illnesswas caused not by badparenting or unresolvedOedipus complexes but bybiological imbalances,organicdisturbancesinthebrain that could becorrected with chemicalinterventions.

Forme, thewatchesofthat long night passedin ghastlywakefulness;

strainedbydread:suchdread as children onlycanfeel.—CHARLOTTEBRONTË,JaneEyre(1847)

As it happens, my owndecades-long experiencewith chemicalinterventionswouldbegin,some twenty-five yearslater,withThorazine.

AsIapproachedtheendof elementary school, myproliferating array of ticsand phobias drove myparents to take me to thepsychiatrichospitalfortheevaluation where it wasdetermined I neededintensive psychotherapy.In seventhgrade, I startedat a new school. OneMonday morning inOctober, I refused to go.

Theprospectofseparationfrom my parents, and ofexposuretogerms,felttooterrifying to endure. Butmy parents, after callingDr. L. (the psychiatristwho had conducted theRorschach test during myevaluation at McLeanHospital and whom I wasnow seeing for weeklypsychotherapy sessions)and Mrs. P. (the social

workerwhowas supposedto be counseling mymother and father abouthow to be less anxiety-inducing parents), refusedtoletmerefuse.Whichledtoamelodramaticstandoffthat would replay itselfmostmorningsfortherestofthatschoolyear.Iwouldwake up crying

and clutching my covers,saying Iwas too scared to

go to school. After failingto reason me out of bed,myparentswouldtearthecovers off, and thewrestling match wouldbegin: my father wouldhold me down while mymother forcedme intomyclothes as I struggled toescape. Then they’d frog-march me out to the carwhile I tried to wrigglefree. During the seven-

minute drive to school, Iwould sob and beg myparents not to make mego.As we’d pull into theschool parking lot, mymoment of reckoningwould arrive: Would myparents have to physicallyremove me from the car,humiliatingme in frontofmerciless schoolmates?Schoolwas terrifying—but

so was the threat ofhumiliation. Wiping mytears,I’dgetoutofthecarand begin the gangplankwalktomyhomeroom.Myanxietywasnot rational; Ihad nothing, really, tofear. Yet anyone who hassuffered the torments ofacute pathological anxietyknows that I am notexaggeratingwhen I say Idonot think Iwouldhave

feltmuchworsehadIbeenwalking to my ownbeheading.Stunned by despair,

blinking back tears,struggling to control myroiling bowels, I’d sitmutely atmy desk, tryingnottoembarrassmyselfbyburstingintosobs.dByJanuary,myphobias

and separation anxietieshad become so consuming

that I had begun to dropmy friends, and they todrop me; I scarcelysocialized with my peersanymore. Engaging in thegive-and-takeofschoolboybanter had become toostressful, soat lunchtimeIpreferred to sit quietlybeside a teacher. This putme in a position, on thefirstdaybackafterholidaybreak that year, to

overhear the Spanishteacher tell the Frenchteacher a graphic tale ofspendingtheholidayswithfriends in Manhattan,where she and hercompanions had beenstricken by a stomachvirus that had includedprolific amounts ofvomiting.eThis was more than I

couldbearonthefirstday

back after vacation; I leftschool, went home, andprettymuchlostmymind.HerearethesnapshotsI

can remember from thatevening: me throwingthings around the house,smashing everything I cangetmyhandson,whilemyfather tries to grapple meinto submission; me lyingon the floor, pounding itwithmyfist, screamingso

hardthatdroolfrothsfrommy mouth, yelling that Iam so scared and can’ttake it anymore andwantto die; my father, on thephonewithDr. L., talkingaboutwhether I shouldbecommitted (there ismention of straitjacketsand ambulances); myfather going to Corbett’s,the local drugstore, andcoming back with

emergency doses ofValium (a minortranquilizer of thebenzodiazepine class,aboutwhichmoreshortly)and liquid Thorazine(whichwasthenknownasamajortranquilizerandisnow classified as anantipsychotic).The Thorazine tastedawful.ButIwasdesperatefor relief, so I drank it in

someorangejuice.Forthenext eighteen months, Iwas on Thorazine aroundthe clock. And startinglater that week, I beganalso taking imipramine,the tricyclic medicationthat was theantidepressant of choiceprior to the arrival ofProzacinthelate1980s.fEvery day for the next

two years, my mother

would place one largeorange Thorazine pill andan assortment of smallergreenandblueimipraminepills on the edge of myplate at breakfast and atdinner. The medicationreduced my anxietyenough to keepme out ofthehospital.Butatacost:on Thorazine, I becamefoggy and dehydrated,shuffling alongwith a dry

mouth and hollowed-outemotions and twitchingfingers, the result of acommon Thorazine sideeffect known as tardivedyskinesia. A year earlier,prior to going onThorazineandimipramine,Ihadbeen selected for anelite soccer team. When Ishowed up the followingautumn in a Thorazinestupor, the coaches were

baffled. What hadhappened to the short kidwho had embarrassedolder players by dribblingcirclesaroundthem?Theynowhad a kid, still short,who moved slowly, tiredeasily,andbecamerapidlydehydrated, a glueywhitemucus encrusted aroundhislips.Evenafter Iwasheavilymedicated, my anxiety

persisted. I’d make it toschool but then getoverwhelmed by fear,leave class, and endup inthe infirmary with theschool nurse, begging herto let me go home.Whenthe confines of theinfirmarycame to feel tooclaustrophobic to containmy antic pacing, shewouldkindlywalkaroundschool with me while I

triedtocalmdown.gSeeing me wandering

thecampuswiththenursewhen I should have beeninclass,mypeersnaturallywonderedwhatwaswrongwithme.Themotherofanerstwhile friend ran intomymother and asked if Iwas ill. My mother,prevaricating, said I wasfine.ButIwasnotfine;Iwas

miserable. In photographsfrom that time, I lookhunchedandhangdogandsickly, like I am shrinkinginto myself. I was onantipsychotics andantidepressants andtranquilizers, and I wastakingdailywalkswiththeschool nurse instead ofattendingclass.Without Thorazine and

imipramine and Valium, I

don’t know that I wouldhave survived seventhgrade. But I did, and bytheendofeighthgrademyanxious misery hadrelented somewhat. Dr. L.weaned me off theThorazine. But since thatwinter some thirty yearsago, I have been on onepsychiatric medication oranother—and often two,three,ormoreatatime—

more or less continuously,making me a livingrepository of thepharmacological trends inanxiety treatment of thelasthalfcentury.

Drug discoveries wereof sensationalimportance forunderstandingpsychiatric illness andthe basic nature of the

human condition: Ourpersonalities, ourintellects, our veryculture couldpresumably be boileddown to a sack ofenzymes.—EDWARDSHORTER,BeforeProzac(2009)

Forabriefperiodinthe1980s,Itookphenelzine,a

monoamine oxidaseinhibitor, orMAOI,whosetrade name is Nardil. Myexperience on MAOIs wasnot notably successful. Ididn’tfeelanylessanxious—but I did do a lot ofworrying about whether Iwould die fromcomplicatingsideeffectsofthe drug. This is becauseMAOIs can havedangerous, even lethal,

side effects, especiallywhen combined with thewrong elements. Whenpatients taking MAOIsingest things—such aswine and other fermentedalcohol, aged cheeses,pickled foods, some kindsof beans, and many over-the-counter medications—that containhigh levelsofan amino acid derivativecalledtyramine,thehealth

effects can be serious:painful headaches,jaundice, a spike in bloodpressure, and in somecases severe internalhemorrhaging. WhichmeansMAOIsmay not beideal for people like mewho are, even in the bestof circumstances, prone tohypochondria and healthanxiety.For this reason, among

others,whiletherearestilldepressed and anxiouspatients for whom MAOIsremain the most, or theonly, effectivepharmacologicaltreatment,MAOIshavenotbeenconsideredafirst-linetreatment for mooddisorders for many yearsnow.h Though MAOIsplayed only a cameo rolein my own psychiatric

history,theyareimportantin the scientific andcultural history of anxietybecause they were amongthe first drugs to bespecifically tied to a just-emerging neurochemicaltheoryofmentalillness.Atmidcentury the advent ofMAOIs, in conjunctionwith the arrival ofimipramine and the othertricyclics (about which

more shortly), helpedcreate the modernscientific understanding ofdepressionandanxiety.MAOIs have their

originsinthelateryearsofthe Second World War,when the GermanLuftwaffe, bombardingEnglish cities with V-2rockets, ran low onconventional fuel and hadto resort to propelling the

rockets with a fuel calledhydrazine. Hydrazine ispoisonous and explosive,but scientists had foundthat they could modify itin ways that might bemedicallyuseful.Whenthewar ended, drugcompanies bought theleftoverhydrazinesuppliesat a steep discount. Theinvestment paid off. In1951,scientistsworkingat

Hoffmann–La Roche inNutley, New Jersey,discovered that twomodified hydrazinecompounds, isoniazid andiproniazid, inhibited thegrowth of tuberculosis.Clinical trials ensued. By1952, both isoniazid andiproniazid were on themarket for treatment oftuberculosis.Buttheseantibioticshad

an unexpected side effect.After being treated withthem,somepatientswouldbecome, as newspapersrecounted, “mildlyeuphoric,” dancingthrough the hallways ofthe tuberculosis wards.Reading these reports,psychiatrists wondered ifthis mood-elevating effectmeant that isoniazid andiproniazid might be used

aspsychiatricmedications.In a 1956 study atRocklandStateHospital inNew York, patients withvarious psychiatricdisorders were giveniproniazid for five weeks;toward the end of thatperiod the depressedpatients had improvedmarkedly. Nathan Kline,the hospital’s researchdirector,observedwhathe

called a “psychicenergizing” effect, and hebegan prescribingiproniazid to themelancholicpatientsinhisprivate practice. Some ofthese patients, hesubsequently reported,experienced “a completeremission of allsymptoms.” Kline wouldlater declare thatiproniazid “was the first

cure in all of psychiatrichistory to act in such amanner.” In April 1957,Hoffmann–LaRochebeganmarketing iproniazid withthe trade name Marsilid,anditwasfeaturedonthefrontpageofTheNewYorkTimes. Marsilid was thefirstoftheMAOIsandoneof the first drugs tobecome known as anantidepressant.

At midcentury thehistory of neuroscience,such as it was, was brief.Knowledge of how thebrain worked wasprimitive. Debate churnedbetween the “sparks” andthe “soups”—betweenthose scientists whobelieved that transmissionof impulses betweenneuronswaselectricalandthosewho believed itwas

chemical.“When Iwas anundergraduate student atCambridge,” LeslieIversen, a professor ofpharmacology at Oxfordrecalled of his time therein the 1950s, “we weretaught … there was nochemical transmission inthebrain—that itwas justanelectricalmachine.”English physiologistshad done primitive

research on brainchemistry in the latenineteenth century. Butnot until the 1920s didOtto Loewi, a professor ofpharmacology at theUniversity of Graz inAustria, isolate the firstneurotransmitter, arguingin a 1926 paper that achemical calledacetylcholine was whatmediated the transmission

of impulses between onenerve ending and thenext.iEven as sales of

Thorazine and Miltownwere taking off, theconcept of aneurotransmitter—of achemical that transmittedimpulses between braincells—had not beendefinitively established.j(The psychiatrists who

prescribed these drugs,and even the biochemistswho developed them,generallyhadnoideawhythe drugs had the effectsthey did.) But discoveriesby two researchers inScotland swung thependulum forcefullytoward the “soups.” In1954, Marthe Vogt, aGerman neuroscientist atthe University of

Edinburgh, discovered thefirst convincing evidenceof a neurotransmitter—norepinephrine. Later thatyear,JohnHenryGaddum,a colleague of Vogt’s,discovered through aseries of unorthodoxexperiments thatserotonin,whichuntilthatpointwas thought to be agut-based compoundinvolved in digestion,was

also a neurotransmitter.kGaddum took LSD—whichhereportedmadehimfeelcrazy for forty-eighthoursandwhich also, accordingto laboratorymeasurements, decreasedthe level of serotoninmetabolites in hiscerebrospinal fluid. Hisbroad conclusion:Serotonin helps keep youmentally healthy—and

therefore a deficiency ofserotonin can make youmentally ill. Thus wasborn theneurotransmitter-based theory of mentalhealth. This wouldtransform the scientificand cultural view ofanxietyanddepression.

Canst thounot…

Raze out the

writtentroubles ofthebrain

And withsome sweetobliviousantidote

Cleanse thestuff’dbosom ofthatperilousstuff

Which weighsupon theheart?—WILLIAMSHAKESPEARE

Macbeth(CIRCA1606)

Bernard “Steve” Brodiehadbuilthisreputationasa biochemist making

antimalarial drugs duringWorld War II. WhenThorazine and Miltowncameonthemarketinthe1950s, he was running alab at the National HeartInstitute of the NationalInstitutes of Health inBethesda, Maryland. Overthe next decade, that labwould revolutionizepsychiatry.Theseminalexperiments

were on reserpine. Anextract from the plantRauwolfia serpentina (itsroot looks like a snake),reserpine had been usedfor more than a thousandyears in India, where itwas prescribed foreverything from highblood pressure andinsomnia to snakebitepoisonings and infantcolic.But ithadalsobeen

used, evidentlywith somesuccess, according toHindu writings, fortreating “insanity.”Reserpine had nevergotten much attention inthe West. But whenThorazine produced suchstriking results, executivesat Squibb wondered ifreserpine could competewith it. They providedfunding to Nathan Kline,

who tested the compoundon a group of his patientsatRocklandStateHospital:several of them improveddramatically, and a fewwhose case reports haddescribed them as“crippled” by anxietybecame relaxed enough toleave the hospital andresumetheirlives.This led to a much

largerstudy.In1955,Paul

Hoch,thecommissionerofmental hygiene for NewYork, arranged withGovernor W. AverellHarriman for $1.5 billionin funding to givereserpine to every singleone of the ninety-fourthousandpatients inallofthe state’s psychiatrichospitals.(FDAregulationswouldneverallowastudylike this to be conducted

today.) The results:Reserpineworkedforsomepatients but not quite aswell as Thorazine—and ithad serious, sometimeslethal, side effects.Clinicians largely set itasideasapsychiatricdrug.But not before Steve

Brodie and his NIHcolleagues had usedreserpine to establish aclear link between

biochemistry andbehavior.InspiredbywhatJohnGaddumhad learnedabout the relationshipbetween LSD andserotonin, Brodie gavereserpine to rabbits to seewhat it did to theirserotonin levels. Brodiefound two interestingthings: administeringreserpine to rabbitsdecreased the amount of

serotonin in their brains,and this decrease inserotonin seemed toproduce rabbitswhowere“lethargic” and“apathetic,”mimickingthebehavior of people wewould today calldepressed. Moreover,Brodie and his colleaguesfound they could induceand diminish “depressed”behavior in the rabbits by

manipulating theirserotonin levels. Brodie’s1955 paper in Sciencereporting these findingswasthefirsttotielevelsofaspecificneurotransmitterto behavioral changes inanimals. Brodie had, asonemedicalhistorianlaterput it,built a bridge fromneurochemistry tobehavior.Brodie’s reserpine

research intersected inintriguingwayswithwhatpsychiatrists were thendiscovering about MAOIs.To oversimplify a little,brain researchers in the1950s were just figuringout that neurotransmittersare discharged by“upstream” neurons intothe synapses—the tinyspacesbetweennervecells—in order to make

“downstream” neuronsfire.Eachneurotransmittertravels quickly from oneneuron to the next,whereit attaches to a receptor—itsmolecularmirrorimage—embedded in theneuron’s membrane. Eachtime one of theseneurotransmitters latchesonto its receptor on thepostsynaptic neuron(serotonin attaching to

serotonin receptors,norepinephrine tonorepinephrine receptors),the receiving neuronchanges shape: itsmembrane becomesporous, allowing atomsfrom the outside of theneurontorush toward theinterior, causing a suddenchange in the neuron’selectric voltage. Thischange causes the

receiving neuron to fire,releasingitsownsupplyofneurotransmitters into thesurrounding synapses.These neurotransmittersthen land on receptors onstill other neurons. Thiscascade of activity—neurons firing, releasingneurotransmitters, causingother neurons to fire—throughout the onehundred billion neurons

and the trillions ofsynapses in our brain iswhat gives rise to ouremotions,perceptions,andthoughts. Neurons andneurotransmitters are, inways scientists are stillstruggling to understand,the physical stuff ofemotionandthought.Early research oniproniazid had revealedthat the antibiotic

inactivated an enzymecalledmonoamine oxidase(MAO), whose function isto break down and clearaway the serotonin andnorepinephrine that buildupinthesynapses.Afteraneurotransmitter issquirted into the synapse,it ordinarily gets quicklycleared out by MAO,allowing for the nexttransmission to happen.

But the“inhibition”of themonoamine oxidaseenzyme by iproniazidallowed theneurotransmitters toremain in the nerveterminalslonger.Theextrabuildup of theseneurotransmitters in thesynapses, Brodie’sresearchers theorized,accounted for iproniazid’santidepressanteffects.Sure

enough,whenrabbitsweregiven iproniazid beforereserpine wasadministered,theserabbitsdid not become lethargicthe way the otherreserpine rabbits did. Theiproniazid, Brodie and hiscolleaguesconcluded,keptthe rabbits from getting“depressed” by boostingthe levels ofnorepinephrine and

serotonin in theirsynapses.This was the moment

the pharmaceuticalindustryawoketotheideathat it could sellpsychiatric drugs bymarketing them ascorrecting “chemicalimbalances,” ordeficiencies of certainneurotransmitters. In oneof its first advertisements

for iproniazid, in 1957,Hoffmann–La Rochepromoted the drug as “anamine oxidase inhibitorwhich affects themetabolism of serotonin,epinephrine,norepinephrine and otheramines.”Research on another

new drug lent furthersupport to this idea. In1954, Geigy, a Swiss

pharmaceutical company,had tweaked Thorazine’schemical structure tocreate the compoundG22355, which it calledimipramine, the firsttricyclic. (Drugs in thiscategoryhavea three-ringchemical structure.)Roland Kuhn, a Swisspsychiatrist who wastrying to develop a bettersleeping pill, had tried

givingimipraminetosomeof his patients. BecauseThorazine and imipraminewere chemically similar(only two atoms weredifferent), Kuhn assumedthat imipramine, likeThorazine, would have asedating effect. It didn’t:rather than puttingpatients to sleep,imipramine energizedthem and elevated their

moods. In 1957, aftertreating more than fivehundred patients withimipramine, Kuhndelivered a paper to theInternational Congress ofPsychiatry in Zurich,reportingthatevendeeplydepressed patients hadimproved dramaticallyafter severalweekson thedrug. Their moods lifted,their energy surged, their

“hypochondriacaldelusions” disappeared,and their “generalinhibition” dissipated.“Not infrequently the cureis complete, sufferers andtheir relatives confirmingthe fact that they had notbeen so well for a longtime,” he declared. Geigytook imipramine out ofmothballs and brought ittotheEuropeanmarket in

1958 under the tradenameTofranil.lOn the day imipraminewasreleasedintheUnitedStates,September6,1959,The New York Timespublished an articleheadlined “Drugs andDepression” about bothMarsilid (iproniazid, thefirst MAOI) and Tofranil(imipramine, the firsttricyclic).TheTimescalled

these drugs “anti-depressants”—seeminglythefirstuseoftheterminthe press or in popularculture.While some estimatesput the number ofAmericans taking anti-depressant medicationstodayatoverfortymillion,therewasnosuchthingasan antidepressant whenRoland Kuhn addressed

the International CongressofPsychiatryin1957.Theconcept simply didn’texist. The MAOIs and thetricyclics had created anewdrugcategory.In the early 1960s,

Julius Axelrod, an NIHbiochemist and a veteranof Steve Brodie’s lab,began to identify theeffects of imipramine onvarious chemicals in the

brain. Axelrod discoveredthat imipramine blockedthe reuptake ofnorepinephrine in thesynapses. (A few yearslater,hewouldfindthatitalso blocked the reuptakeof serotonin.) Axelrodtheorized thatantidepressants’ effect onthe reuptake ofnorepinephrine was whataccounted for the

elevationofmoodandtherelief of depression. Thiswasa transformative idea:if imipramine blocked thereuptake ofnorepinephrine, and if itmadepatients lessanxiousanddepressed, thatmeanttheremustbeacorrelationbetween norepinephrineand mental health.Marsilid or Tofranil—orcocaine, for that matter,

which has a similar effect—seemed to cure anxietyanddepressionbyboostingthe levels ofnorepinephrine in thesynapses, delaying itsreuptakeintotheneurons.Around this time,

Joseph Schildkraut was apsychiatrist at theMassachusetts MentalHealth Center whobelieved that anxiety and

psychoneurosis werecaused by childhoodtrauma or unresolvedpsychic conflicts andweretherefore best treated byFreudian psychotherapy.Then he gave imipramineto a few of his patients.“These drugs seemed likemagic to me,” he wouldsaylater.“Ibecameawarethat there was a newworldoutthere,aworldof

psychiatry informed bypharmacology.” In 1965,he published an article inThe American Journal ofPsychiatry, “TheCatecholamine Hypothesisof Affective Disorders: AReview of the SupportingEvidence”;buildingonthework of Steve Brodie andJulius Axelrod, he arguedthatdepressionwascausedbyelevatedbrainlevelsof

catecholamines, the fight-or-flight hormones (suchas norepinephrine) thatarereleasedbytheadrenalglands in times of stress.Schildkraut’s paperbecame one of the mostcitedjournalarticlesinthehistory of psychiatry,enshrining the chemicalimbalance theory ofanxiety and depression atthecenterofthefield.

The first pillar ofbiological psychiatry hadbeen constructed. TheFreudian model ofpsychiatry had sought totreat anxiety anddepression by resolvingunconscious psychicconflicts. With the adventof the antidepressants,mental illness andemotional disorders wereincreasingly attributed to

malfunctions of specificneurotransmitter systems:schizophrenia and drugaddictionwerebelievedtobe caused by problems inthe dopamine system;depression was aconsequence of stresshormones released by theadrenal glands; anxietyresulted from defects intheserotoninsystem.But pharmacology’s

most transformative effecton the history of anxietywas still to come,beginning with studies onimipramine that wouldreshape the psychiatricestablishment’sunderstandingofanxiety.

* Actually, Dr. Stanford alsoconceded a strong biologicalcomponent to anxiety; her view

wasthatbiologycanbeovercomeby cognitive retraining. Andresearch does suggest thatcognitive retraining, as well asother forms of talk therapy, canchange biology in the same waythat medication does, sometimesmore profoundly and enduringly—a literalmanifestation ofmindovermatter.

† Freud was also, by his ownadmission, addicted to nicotine,smokingtwentyormorecigarsa

day for most of his life, a habitthat would reward him withmouthcancerinhissixties.

‡ Some doctors prescribed straightalcohol. In the 1890s, AdolphusBridger, an influential Londonphysicianand theauthorof suchpopular medical books as TheDemonofDyspepsia andManandHis Maladies, told patientssuffering from tension andmelancholy to drink port andbrandy.Hewrotethat“asuitable

form of alcohol”—especially“full-bodiedBurgundy,highclassclaret, port, the better whiteFrench, German, and Italianwines, stout or good brandy”—would “do more to restorenervous health” than any othermedicine.

§ Two years later, Bayer broughtout another analgesic,acetylsalicylic acid, under thebrand name Aspirin. In time, asHeroin and Aspirin became

ubiquitous,bothwentfrombeingbrand names to generic terms.Turn-of-the-century physicians inAmerica and England had asomewhat backwardunderstanding of thesemedications, often giving Herointotheirpatientsforphysicalpain(which, in fairness, made acertain sense) and administeringAspirin for “nervousness” (whichdidnot).

‖ Potassium bromide, a compound

introduced at a British medicalconference in 1857, wasoriginally used as an antiseizuremedication and was, from thelate nineteenth century into theearly twentieth, popular as asedative. Eventually, the toxicityand side effects of bromides,ranging from a bitter aftertasteand acne to dizziness, severenausea,andvomiting,ledtotheirabandonment (today they areused almost exclusively in

veterinarymedicine fordogsandcatswith epilepsy), but theirusewas widespread enough for longenough that theword “bromide”also came to mean a soporificplatitude. Chloral hydrate, asleep-inducing agent firstsynthesized in 1832, was addedtodoctors’psychotropictoolkitin1869 after Otto Liebrich, aprofessor of pharmacology inBerlin, gave the substance tomelancholic patients and

observed that it alleviated theirinsomnia.A hundred years later,my great-grandfather would beprescribedchloralhydrateforhistension and insomnia. (Chloralhydratewasalsooneoftheactiveingredients, along with alcohol,in the Mickey Finn, a doctoreddrink that often featured inDepression-erapotboilers.)

aCrisalida, an undulating two-and-a-half-ton tunnel meant tosymbolize the Miltown-aided

passagetowhatthepaintercalled“thenirvanaof thehumansoul,”stoodintheexhibitionhallattheannual meeting of the AmericanMedical Association in 1958,surely one of the more avant-garde exhibits ever to grace amedicalconvention.

bFirstsynthesizedasabluedyeinthe 1880s, phenothiazine,chlorpromazine’s parentcompound,wasover thedecadesthat followed discovered to have

an unlikely array of medicinalproperties: it worked as anantiseptic (reducing the risk ofinfection), an anthelmintic(expelling parasitic worms fromthe body), an antimalarial(combating malaria), and anantihistamine(preventingallergicreactions). Capitalizing on itsbug-killing powers, DuPontstarted selling phenothiazine tofarmersasaninsecticidein1935.

c This revolutionized psychiatry.

Before 1955, both the acutelypsychotic and the moderatelyneurotic were treated mainly bypsychoanalysis or something likeit; the working out ofpsychologicalissuesorchildhoodtraumas in talk therapy was theaccepted route tomental health.“No one in their right mind inpsychiatry was working ondrugs,” Heinz Lehmann wouldlater say of the field before the1950s. “You used shock, or

variouspsychotherapies.”

d My first glimpse of clinicaldepression came as I was sittinginclassoneFridayafternoonthatyear. I was experiencing mycharacteristic relief at theprospect of being sprung for theweekendwhenIhadthethoughtBut on Sunday night this starts allover again, and I was chilled bythe infiniteness of my plight, bythe notion that Sunday nights—andMondaymornings—eternally

return,andthatonlydeathwouldput a stop to them, and thattherefore there was nothing,ultimately, to look forward tothatmighthelpmetranscendmydreadaboutbadthingstocome.

eYes,itisamarkoftheintensityofmy phobic preoccupations that Ican today, some thirty yearslater, still remember theconversationalmostverbatim.

fImipraminedidmoretodeterminethe modern conception of panic

anxiety than any other drug.(More about that in the nextchapter.)

gCompoundingmatters,myphobiaof vomiting metastasized aroundthistimeintoafearofchoking;Istarted having troubleswallowing. (Difficulty inswallowing has been a well-recognized symptom of anxietysince at least the late nineteenthcenturyandisknownclinicallyasdysphagia.) I became afraid to

eat.My skinnyadolescent frame,worn ever thinner by nervousfidgeting, became emaciated. Istopped eating lunch at school.The more trouble I hadswallowing, the more I’d obsessabout my trouble swallowing,and theworse the troublewouldget. Soon I was having troubleswallowingevenmysaliva.I’dsitthere in history class,mymouthfullofspit,terrifiedthatifIwerecalled upon to speak, I would

choke on my mouthful of salivaor spew it all over my desk—orboth. I took to carrying wads ofKleenex around with meeverywhere I went, discreetlydrooling into them so that Iwouldn’t have to swallow. Bylunchtime each day, my pocketswouldbefullofdrenchedtissues,whichwouldleachintomypantsandmake themsmell like saliva.Over the course of the day, thetissues would disintegrate, so by

evening bits of slobbery Kleenexwould be spilling out of mypockets.

AreyousurprisedtolearnthatI had but one date in all ofmiddleschoolandhighschool?

h After trying many alternativeremedies, including electroshocktherapy,thenovelistDavidFosterWallace found Nardil to be themost effective treatment for hisanxietyanddepression.GoingoffNardil, after experiencing what

seems to have been a tyramine-induced side effect, may haveprecipitatedWallace’s downwardspiraltosuicidein2008.

i Loewi famously claimed heconceived the experiment,whichinvolved artificially raising andlowering the heart rate of frogs,in a dream he had on EasterSunday 1923. Thrilled, hescribbled the experiment on apiece of paper by his bed—onlyto awake the next morning to

find that he could neitherrememberhisdreamnordecipherhis own handwriting.Fortunately,hedreamedthesameexperiment the following night.This time he remembered it,performed it, and demonstratedfor the first time the chemicalbasis of nerve transmission—workforwhichhewouldlaterbeawardedaNobelPrize.

jOtto Loewi andothers had foundsuggestive evidence of

neurotransmitters such asnorepinephrine in thebloodstream—butnoonehadyetisolatedanyinthebrain.

kAbriefhistoryof early serotoninresearch: In 1933, the Italianresearcher Vittorio Erspamerisolatedachemicalcompound inthe stomach that he namedenteramine because it seemed topromote the gut contractioninvolved in digestion. In 1947,two American physiologists

studying hypertension at theCleveland Clinic foundenteramineintheplateletsoftheblood. Noticing that enteraminecaused blood vessels to contract,they renamed the compoundserotonin (sero for “blood,” fromthe Latin word serum, and toninfor muscle tone, from the Greekword tonikos, tonic). In 1953,when researchers for the firsttime found tracesof serotonin inthe brain, they still assumed it

was merely the residue of whathad been carried through thebloodstream from the stomach.Only in the ensuing years didserotonin’s role as aneurotransmitterbecomeevident.

l Imipramine might never havemade it to pharmacies—and thehistory of biological psychiatrymighthavebeenquitedifferent—if not for another accident ofhistory. Kuhn’s presentation tothe International Congress of

Psychiatrywasmet,asheput it,“withagreatdealof skepticism”because “of the almostcompletelynegativeviewofdrugtreatmentofdepressionuptothattime.” In fact, suchwas the lackof psychiatric interest in drugsthatonly twelvepeople attendedKuhn’s talk in Zurich. (His talkhas sincebeen referred to as theGettysburg Address ofpharmacology—littlenotedatthetime but destined to become a

classic.) Geigy, too, wasunimpressed. The companyshared psychiatry’s skepticismaboutamedicinethatcouldtreatan emotional disorder. It had noplans tomarket imipramine. Butone day Kuhn happened to runintoRobertBohringer,apowerfulGeigy shareholder, at aconference in Rome. WhenBohringermentionedthathehada deeply melancholic relative inGeneva, Kuhn handed him a

bottle of imipramine. Within afew days of starting on it,Bohringer’s relative hadrecovered. “Kuhn is right,”Bohringer declared to Geigyexecutives. “Imipramine is anantidepressive.” Geigy executivesrelentedandbrought thedrugtomarket.

CHAPTER6

ABriefHistoryofPanic;or,HowDrugsCreatedaNewDisorder

Ananxietyattackmay

consist of a feeling ofanxiety alone, withoutany associated ideas,or accompanied by theinterpretation that isnearest to hand, suchas the ideas of theextinction of life, or astroke,or the threatofmadness,or the feelingof anxiety may havelinked to it adisturbance of one or

more of the bodilyfunctions—such asrespiration, heartaction, vasomotorinnervation orglandular activity.From this combinationthepatientpicksout inparticular now one,now another, factor.He complains of“spasms of the heart,”“difficulty in

breathing,” “outbreaksof sweating,” … andsuchlike.—SIGMUNDFREUD,“ONTHEGROUNDSFORDETACHING

APARTICULARSYNDROMEFROMNEURASTHENIA

UNDERTHEDESCRIPTIONOF

ANXIETYNEUROSIS”(1895)

The bases of mentalillness are chemicalchanges in the brain.… There’s no longeranyjustificationforthedistinction … betweenmind and body ormental and physicalillness.Mental illnessesarephysicalillnesses.—DAVIDSATCHER,U.S.SURGEONGENERAL

(1999)

OnedayIamsittinginmyofficereadinge-mailwhenvaguely, at the edges ofmy awareness, I notice Iamfeelingslightlywarm.Is it getting hot in here?

Suddenlyawarenessoftheworkings of my bodymovestothecenterofmy

consciousness.Do I have a fever? Am Igettingsick?WillIpassout?Will I vomit?Will I, in oneway or another, beincapacitated before I canescapeorgethelp?I am writing a bookabout anxiety. I amsteeped in knowledge ofthe phenomenon of panic.I know as much as anylayperson about the

neuromechanics of anattack. I have hadthousands of them. Youwould think that thisknowledge and experiencewould help. And, to besure, occasionally it does.By recognizing thesymptoms of a panicattack early on, I cansometimes head it off, oratleastrestrictittowhat’sknown as a limited-

symptompanicattack.Buttoo often my internaldialogue goes somethinglikethis:You’rejusthavingapanic

attack.You’refine.Relax.But what if it’s not a

panic attack? What if I’mreallysickthistime?WhatifI’mhavingaheart

attackorastroke?It’salwaysapanicattack.

Doyourbreathingexercises.

Staycalm.You’refine.ButwhatifI’mnotfine?You’re fine. Every one of

thelast782timeswhenyouwere having a panic attackandyouthoughtitmightnotbe a panic attack, it was apanicattack.Okay. I’m relaxing.

Breathing in and out.Thinking the calmingthoughts the meditationtapes have taught me. But

just because the last 782instanceswerepanicattacks,thatdoesn’tmeanthe783rdone is too, right? Mystomachhurts.You’re right. Let’s get

outtahere.Sitting in my office

while something like thissequenceofthoughtsflowsthrough my head, I gofrom feeling moderatelywarm to feeling hot. I

begin to perspire. The leftside of my face starts totingle, then goes numb.(See,Isaytomyself,maybeI am having a stroke!) Mychest tightens. I amsuddenly aware that thefluorescent lights in myoffice have a strobelikequality and are flickeringdizzyingly. I feelaterriblevertiginous teetering, likethe furniture in my office

is moving around, like Iam about to toppleforwardontotheground.Igrip the sides ofmy chairfor stability. As mydizzinessincreasesandmyoffice swirls around me,my physical surroundingsno longer feel quite real;it’s as though a scrim hascomebetweenmeandtheworld.My thoughts race, but

the three most prominentare: I’m going to vomit. I’mabout to die. I’ve got to getoutofhere.I bolt unsteadily from

my chair, perspiringheavilynow.Allmy focusisonescape: Ineedtogetout—outofmyoffice, outofthebuilding,outofthissituation. If I’m going tohave a stroke or vomit ordie,Iwanttobeoutofthe

building. I’m going tomakeabreakforit.Desperately hoping that

I’m not accosted on myway to the stairs, I openthe door and sprint-walkto theelevatorvestibule. Ipushthroughthefiredoortothestairwelland,withasmall feeling of relief athaving made it this far,begin to climb sevenflightsdown.BythetimeI

reach the third floor, mylegsarequaking. If Iwerethinking rationally—if Icould calm my amygdalaandmakebetteruseofmyneocortex—I wouldconclude, correctly, thatthisquaking is thenaturalresult of an autonomicfight-or-flight response(whichcausestremblinginthe skeletal muscles)combined with the effects

of physical exertion. Buttoo far gone into thecatastrophizing logic ofpanictoaccessmyrationalbrain, I conclude insteadthatmyquakinglegsareasymptom of completephysical breakdown andthat I am indeed about todie.As Idescend the finaltwo flights, I amwondering whether I willbe able to reach my wife

frommycellphoneto tellher I love her and to askher to send help before Ilose consciousness andpossiblyexpire.The door from the

stairwell to the outside iskept locked. Motiondetectors are supposed tosenseyoucomingfromtheinside and automaticallyunlockit.Forsomereason,perhaps because I am

going too fast, they fail toactivate. I slam into thedoor at high speed andbounce off, fallingbackwardontomyrear.Ihavehitthedoorwith

sufficient force todislodgethe plastic frame aroundthe exit sign glowing redabove it. The frame fallsontomyheadwitha thudand then clatters to thefloor.

The lobby securityguard, hearing the racket,pokes his head into thestairwelltofindmesittingonthefloorinadaze,theexitsignframebymyside.“What’sgoingoninhere?”hesays.“I’m sick,” I say, andwho would say that I amnot?

The ancient Greeksbelieved thatPan, thegodof nature, ruled overshepherds and theirgrazingflocks.Panwasnota noble god: hewas shortand ugly, ran on stubbygoatlike legs, and liked totake naps in caves orbushes by the side of theroad. When awakened bypassersby, he would issuea bloodcurdling scream

that made the hair ofanyonewhohearditstandon end. Pan’s scream, itwas said, caused travelersto drop dead from fright.Paninducedterroreveninhis fellow gods.When theTitans assaulted MountOlympus (as myth wouldhave it),Panassured theirdefeat by sowing fear andconfusion in their ranks.The Greeks also credited

Pan with their victory atthe Battle of Marathon in490 B.C., where he wassaidtohaveputanxietyinthe hearts of the enemyPersians.Theexperienceofsudden terror—especiallyin crowded places—became known as panic(from the Greek panikos,literally“ofPan”).Anyone who has

suffered the torments of a

panic attack knows theturmoil it can unleash—physiological as well asemotional. Thepalpitations.Thesweating.Theshaking.Theshortnessof breath. The feeling ofchoking and tightness inthe chest. The nausea andgeneral gastric distress.Thedizzinessandblurringof vision. The tinglingsensations in the

extremities (“paresthesias”is the medical term). Thechills andhot flashes.Thefeelings of doom andgaping existentialawfulness.*David Sheehan, apsychiatrist who hasstudied and treatedanxiety for forty years,tells a story that captureshow awful the experienceof panic can feel. In the

1980s, a World War IIveteran, one of the firstinfantrymen to land atNormandyonD-day,cameto see Sheehan, seekingtherapy for panic attacks.Wasn’t the experience ofstorming the beach atNormandy, Sheehan askedhim,bulletsandbloodandbodies flying and fallingall around him—with theprospectofhisown injury

or death quite real, evenlikely—more frighteningand miserable thanenduringapanicattackatthe dinner table, howeverravaged he might feel bythe neurotic circuitry ofhis ownmind? Not at all,themansaid.“Theanxietyhe felt landing on thebeaches was mildcompared to the sheerterror of one of his bad

panic attacks,” Sheehanreports. “Given the choicebetweenthetwo,hewouldgladly again volunteer tolandinNormandy.”

Today,panicattacksareafixture of psychiatricmedicine and of popularculture.Asmanyaselevenmillion Americans todaywill, like me, at some

point be formallydiagnosed with panicdisorder.Yetasrecentlyas1979,neitherpanicattacksnor panic disorderofficially existed. Wheredid these concepts comefrom?Imipramine.In 1958, Donald Klein

wasayoungpsychiatristatHillside Hospital in NewYork. When imipramine

becameavailable,heandacolleague beganadministeringitwilly-nillyto most of the twohundred psychiatricpatients in their care atHillside. “We assumed itwould be some sort ofsupercocaine, blasting thepatients out of their rut,”Klein recalled.“Remarkably, theseanhedonic, anorexic,

insomniac patients beganto sleep better, eat better,after severalweeks … saying ‘the veilhaslifted.’”What most interestedKleinwas that fourteenofthese patients—who hadpreviously been sufferingfrom intermittent acuteepisodes of anxietycharacterized by “rapidbreathing, palpitations,

weakness,anda feelingofimpending death”(symptoms of what wasthen called, in theFreudiantradition,anxietyneurosis)—experiencedsignificant or completeremission of their anxiety.One patient in particulardrew Klein’s attention. Hewould rush in a panic tothe nurses’ station, sayinghewasafraidhewasabout

todie.Anursewouldholdhis hand and talk to himsoothingly, and within afew minutes the attackwould pass. This recurredeveryfewhours.Thorazinehadn’tworkedforhim.Butafter the patient had beenon imipramine for a fewweeks, the nurses noticedthat his regular panickyvisits to their stationstopped.Hestillreporteda

generally high level ofchronic anxiety, but theacute paroxysms of it hadstoppedcompletely.This got Klein thinking.

That imipramine couldblock paroxysmal anxietywithout stopping generalanxiety or chronicworrying suggested therewassomethingwrongwiththe prevailing theory ofanxiety.

When Freud had hungouthisshingleasa“nervedoctor” in the late 1880s,the most commondiagnosis among thepatients he and his peerssaw was neurasthenia, aterm popularized by theAmerican physicianGeorge Miller Beard torefer to the mixture ofdread, worry, and fatiguethat Beard believed the

stresses of the IndustrialRevolution had produced.The root cause ofneurasthenia was thoughttobenervesthathadbeenoverstrained by thepressures of modern life;the prescribed remediesfor these “tired nerves”were“nerverevitalizers”—nostrums such as mildelectrical stimulators orelixirs tinged with opium,

cocaine, or alcohol. ButFreud became convincedthat the feelings of dreadand worry that he wasseeing in the neurasthenicpatientsheconsultedwerebased not in tired nervesbut in problems of thepsyche, which could beresolved throughpsychoanalysis.In 1895, Freud wrote apaper about anxiety

neurosis, a condition hesought to differentiatefrom neurasthenia andwhose symptoms, as hedescribed them, conformquitecloselytotheDSM-Vchecklist for panicdisorder:rapidorirregularheartbeat,hyperventilationand breathingdisturbances, perspirationand night sweats, tremorand shivering, vertigo,

gastrointestinaldisturbances,andafeelingofimpendingdoomthathecalled “anxiousexpectations.”Nothing in all thisnecessarily contradictedanythingthatDonaldKleinwouldlatergleanfromhisimipramine experiments.Butthat’sbecausein1895Freud still consideredanxiety neurosis to be the

productnotofa“repressedidea” (which is what hebelieved underlay mostpsychopathology) but of abiological force. Anxietyneurosis, Freud theorizedin these early writings,was the result of eithergenetic predisposition (atheory that modernmolecular geneticssupports) or some kind ofpent-up physiological

pressure—mostnotably, inFreud’s imagining, thepressure caused bythwartedsexualdesire.But in many of hissubsequent writings(starting with Studies onHysteria from around thissametime),Freudassertedinstead that attacks ofanxiety—even ones thatmanifested themselves inacutephysicalsymptoms—

emanated fromunresolved, and oftenunconscious, innerpsychicconflicts. For nearly thirtyyears, Freud effectivelyabandoned the argumentthatanxietyattackswereabiologicalproblem.Heandhis followers replacedanxietyneurosiswithplainneurosis—a problem thathad its basis in psychicdiscord, not in genes or

biology. By the mid-twentieth century, theoverwhelming psychiatricconsensuswasthatanxietywastheresultofaconflictbetween thedesiresof theid and the repressions ofthe superego—and that,furthermore, anxiety wasthe foundation of almostall mental illness, fromschizophrenia topsychoneuroticdepression.

One of themain purposesof psychoanalysis—and ofmostformsoftalktherapy—was to help the patientbecome aware of andcontend with theunderlying anxiety againstwhich all of his variousmaladaptive “egodefenses” had beenmustered. “Thepredominant Americanpsychiatrictheorywasthat

all psychopathology wassecondary to anxiety,”Klein later recalled,“whichinturnwascausedbyintrapsychicconflict.”But this didn’t squarewith what Klein wasfinding in his imipraminestudies. If anxietywas theanimating forcebehindallpsychopathology, thenwhy didn’t imipramine—whichseemedtoeliminate

the panic suffered bypatients with anxietyneurosis—helpschizophrenics with theirpsychosis? Maybe, Kleinventured, not all mentalillnesses lay on thespectrum of anxiety thewaytheFreudiansthoughttheydid.The spectrum theory of

anxiety held that whatdetermined a mental

illness’s severity was theintensityoftheunderlyinganxiety: mild anxiety ledto psychoneurosis andvariousneuroticbehaviors;severe anxiety led toschizophrenia or manicdepression. For manytraditional Freudians, thesettings—like bridges orelevators or airplanes—that tended to produceacute anxiety attacks had

symbolic,andoftensexual,significancethataccountedfor the anxiety theycaused.Balderdash, Klein said.Childhood trauma orsexual repression didn’tcause panic; a biologicalmalfunctiondid.Klein concluded thatthese attacks ofparoxysmal anxiety—which he would come to

call panic attacks—originated in a biologicalglitch that produced asuffocation alarmresponse, his term for thecascade of physiologicalactivity that leads to,among other things, whatfeels like a spontaneousattack of overwhelmingterror. Anytime someonestarts to asphyxiate,internal physiological

monitors detect theproblem and sendmessages to the brain,causing intense arousal,gaspingforbreath,andanurge to flee—an adaptivesurvival mechanism. Butsome people, according toKlein’s false suffocationalarm theory, havedefective monitors thatoccasionally fire evenwhen the individual is

getting enough oxygen.This causes the person toexperience the physicalsymptomsthatmakeupananxiety attack. The sourceof panic is not psychicconflict but crossedphysiological wires—wiresthat imipramine somehowuntangled. Klein’s datasuggested that imipramineeliminated spontaneousanxiety attacks in most

patients who sufferedthem.When Klein publishedan initial report onimipramine in TheAmerican Journal ofPsychiatry in 1962, it wasreceived, as he recalled,“like the proverbial leadballoon.” Subsequentarticles over the nextseveral years, inwhichheargued that panic anxiety

wasanillnessdistinctfromchronic anxiety, werereceived with similarfroideur. He was attackedfrom all sides, accused ofbeing an apostate. Butbecause imipramineseemed to cure panicanxiety without affectingfeelings of generalapprehension andneurosis, Klein remainedconvinced that panic

anxietyhadsymptomsandphysiological causes thatweredifferent inkindandnot just in degree fromotherformsofanxiety.Thoughhehadn’tsetout

to, Klein had achievedwhat’s known as the firstpharmacologicaldissection: workingbackward from the effectsof drug treatment, he haddefined a new illness

category,carvingoutpanicanxiety from the moregeneral anxiety that wassupposed to underlie theFreudianneuroses.Klein’s pharmacologicaldissection of anxiety metwith enormous hostilityfrom his colleagues. At aconferencein1980,justasthe publication of theDSM-IIIwasbringingpanicdisorder into existence,

Klein’s presentation onhow the suffocation alarmresponse caused panicanxiety was followedimmediately by a lecturefrom John Nemiah, thelongtime editor of theprestigious AmericanJournal of Psychiatry.Rebutting Klein, Nemiahsaidthatpanicanxietyhadnothing to do with asuffocationalarmresponse

or problems of biologicalhardwiring but ratherwas“the reaction of theindividual’s ego … to thethreatenedemergence intoconscious awareness ofunpleasant, forbidden,unwanted, frighteningimpulses, feelings, andthoughts.”Though Klein’s theory

has been to some degreeofficially adopted by

American psychiatry since1980, it remainscontroversial today. Myown current therapist, Dr.W., a PhD psychologistwhodidhistraininginthe1960s,lamentsthatKlein’sworkledtoafundamentalshift in how we thinkabout mental illness,moving us from thedimensional model thatprevailed through the age

of the DSM-II to thecategorical model thatbeganwiththepublicationof the DSM-III in 1980.According to thedimensional model,depression, neurosis,psychoneurosis, panicanxiety, general anxiety,social anxiety, obsessive-compulsive disorder, andso forth all exist along aspectrum emanating from

the same roots in whatFreud called intrapsychicconflicts(orDr.W.’s“self-wounds”). According tothe categorical model, aslaid out in theDSM sinceits third edition,depression, panic anxiety,general anxiety, socialanxiety, obsessive-compulsive disorder, andsofortharecarvedupintodiscrete categories based

on distinctive symptomclusters that are believedto have differentunderlyingbiophysiologicalmechanisms.Between 1962, whenKlein published his firstimipramine study, and1980, when the DSM-IIIwas published, the waypsychiatry(andtheculturegenerally) thought about

anxiety underwent anenormous transformation.“It is hard to recall thatfifteenortwentyyearsagotherewasnosuchconcept[as panic anxiety],”marveled Peter Kramer, apsychiatrist at BrownUniversity, in his 1993book, Listening to Prozac.“Neitherinmedicalschoolnor psychiatry residency,both in the 1970s, did I

ever meet a patient with‘panicanxiety.’”Yettodaypanic disorder is afrequently diagnoseddisease (some 18 percentofAmericansareestimatedto suffer from it), and“panic attack” hastranscended thepsychiatric clinic tobecomepart of our linguafranca.Panic disorder was the

firstpsychiatricdiseaseforwhich the determiningfactorinitscreationwasadrug reaction: imipraminecures panic; ipso factopanic disorder must exist.But this phenomenon—inwhich a drug effectivelydefined the syndrome forwhich it was prescribed—wouldsoonrecur.

DSMassigns each slice

of craziness with aname and a number.Panic disorder, forexample, is diseasenumber 300.21, adiagnostic code.… Butjust because it has aname, is it actually adisease?—DANIELCARLAT,

Unhinged:TheTroublewithPsychiatry—a

Doctor’sRevelationsAboutaProfessioninCrisis(2010)

Anadvertisement foranOctober 1956 public talkby Frank Berger, theinventor of Miltown,stated that tranquilizerswere effective in treatinghigh blood pressure,worry, jitters, “executivestomach,” “boss nerves,”

and “housewife nerves.”None of these ailmentswere then, or are now,listed as illnesses in theAmerican PsychiatricAssociation’s Diagnosticand Statistical Manual—which raises the questionof whether Miltownprescriptions were aimedless at treating actualpsychiatric disorders thanat treating theage itself—

atmitigatingtheeffectsofwhat Berger in this talkcalled “today’s pressureliving.”Every time new drug

therapiescomealong,theyraisethequestionofwherethelinebetweenanxietyaspsychiatric disorder andanxiety as a normalproblem of living shouldget drawn. We see thisagain and again

throughout the history ofpharmacology: the rise oftranquilizersisfollowedbyan increase in anxietydisorders diagnoses; therise of antidepressants isfollowedbyanincreaseintherateofdepression.WhentheAPApublished

thefirsteditionoftheDSMin the aftermath ofWorldWar II, the governinginfrastructure of the

profession was stillFreudian: the first editionplaced all disorders alonga spectrum of anxiety.“Thechiefcharacteristicof[neurotic] disorders is‘anxiety,’ ” the manualdeclared, “which may bedirectly felt and expressedor which may beunconsciously andautomatically controlledby the utilization of

various defensemechanisms.” The secondedition,publishedin1968,was even more explicitlypsychoanalytic. When theAPAdecided in the 1970sthatitwastimeforathirdedition, the Freudians(who had dominated thetask forces that wrote thefirst two editions) and thebiological psychiatrists(who had gotten a boost

fromtherecentfindingsofpharmacology research)prepared for a pitchedbattle.The stakes were high.

Doctors and therapists ofdifferentschoolswouldseetheir professional fortunesrise or fall depending onwhether the definitions ofthe diseases theyspecialized in werenarrowed or expanded.

Drug company profitswould spike or plummetdependingonwhether thecategories that werecreated could be targetedby—andcouldhelpsecureFDA approval for—themedications theymanufactured.The publication of the

DSM-III in 1980represented at least apartial repudiation of

Freudian concepts and avictory for biologicalpsychiatry. (One medicalhistorian called the DSM-III a “death thrust” forpsychoanalysis.) Out wentthe neuroses, and in theirplace came the anxietydisorders: social anxietydisorder, generalizedanxiety disorder, post-traumatic stress disorder,obsessive-compulsive

disorder, and both panicdisorder with agoraphobiaandpanicdisorderwithoutagoraphobia. DonaldKlein’s pharmacologicaldissection of panic hadprevailed.†But in moving mentalillness away fromFreudianism and into therealm of medicaldiagnosis, the new DSMpathologized as

“disordered”or “ill”manypeople who once wouldhave been consideredmerely “neurotic.” Thiswas a boon for the drugcompanies,whichnowhadmany more “sick” peoplefor whom to develop andmarket medication. Butdiditbenefitpatients?That’s a complicatedquestion.Ontheonehand,the medicalization of

depression and anxietyhelped destigmatizeconditions once regardedas shameful characterweaknesses,anditallowedpeopletofindrelief(oftenpharmacological) fromtheir misery. The numberof people seeingdepression or anxietydisorders as a healthproblem—as opposed toevidence of personal

weakness—grewdramatically between1980 and 2000, as Prozacand other SSRIs providedadditionalevidencefortheidea of depression as aproblem of chemicalimbalance.‡ On the otherhand, the expansion ofmedical categories ofmental illness had theeffectofdrawingcountlessmentally healthy people

into the nets of thepharmaceuticalcompanies.Before the arrival ofMAOIsandtricyclicsinthelate 1950s, depression(and its predecessors)wasa rare diagnosis, given toonlyabout1percentoftheU.S.population.Today,bysomeofficialestimates,it’sa diagnosis given toup to15 percent of us. Are wetruly that much more

depressedin2011thanwewerein1960?Orhavewedefined depression andanxiety disorders toobroadly,allowingthedrugcompanies to bamboozleus (and our insurancecompanies)intopayingforpills thattreatdiseaseswedidn’t know we had,diseases that didn’t existbefore1980?The publication of each

successive edition of theDSM has intended toconvey the impression ofscienceadvancing.And,tobesure,theDSM-III,DSM-IV (which came out in1994), andDSM-V (whichcame out in 2013) weremoreempiricallygroundedthanthefirsttwoeditions.They placed much lessinfluence on etiology—that is, on the presumed

causesofdifferentillnesses—and much more onsimple symptomdescription.§Buttheywerestillpoliticaldocumentsasmuch as scientific ones,representing the claims ofonepsychiatricschooloveranother—and theprofessional interests ofpsychiatrists aboveeverything else. “It is thetask of the APA”—and

therefore of theDSM—“toprotect the earning powerof psychiatrists,” PaulFink, thevicepresidentofthe American PsychiatricAssociation, declared in1986.StuartKirkandHerbKutchins, social workerswhohavetogetherwrittentwo books about thehistory of the DSM, saythat the APA’s so-calledbible is “a book of

tentatively assembledagreements” that has ledto the “pathologizing ofeverydaybehaviors.”When you probe more

deeply into the processthatproducedtheDSM-III,itspretensionstoscientificrigorbegin to seemratherstrained.Forstarters,someof its new categorydistinctionsappearawfullyarbitrary.(Whydoespanic

disorder require thepresence of foursymptoms, rather thanthreeor five, fromthe listof thirteen? Why dosymptoms have to persistfor six months, and notfive or seven, for anofficial diagnosis of socialanxiety disorder?) Thehead of the DSM-III taskforce, Robert Spitzer,would concede years later

that many of its decisionsweremadehaphazardly.Ifa constituency lobbiedhardenoughforadisease,it tended to getincorporated—whichhelpsexplain why between itssecond and third editionstheDSMgrewfrom100to494pagesandfrom182to265diagnoses.David Sheehan workedon theDSM-III task force.

One night in the mid-1970s, Sheehan recalls, asubsetofthetaskforcegottogether for dinner inManhattan. “As the wineflowed,”Sheehansays,thecommitteememberstalkedabout how Donald Klein’sresearch showed thatimipramine blockedanxiety attacks. This didseem to bepharmacological evidence

of a panic disorder thatwas distinct from otherkinds.AsSheehanputsit:

Panic disorder wasborn. And then thewine flowed somemore, and thepsychiatrists aroundthe dinner tablestarted talking aboutone of theircolleagueswhodidn’t

suffer from panicattacks but whoworried all the time.How would weclassifyhim?He’sjustsort of generallyanxious. Hey, howabout ‘generalizedanxiety disorder’?Andthentheytoastedthe christeningof thedisease with the nextbottle of wine. And

then for the nextthirtyyearstheworldcollecteddataonit.

Sheehan,atall Irishmanwho today runs apsychiatric center inFlorida, is regarded assomething of an apostateby the profession. Hecheerfullyadmitsheisoutto “sabotage the notion”thatpanicdisorderistruly

distinct from generalizedanxiety disorder. So hisjaundiced version of howgeneralized anxietydisorder was born shouldperhaps be viewed withsome skepticism. ButSheehan, who has beenstudying and treatinganxietyfordecades,makesan important point: Onceyou create a new disease,itstartstotakeonalifeof

its own. Research studiesaccrete around it, andpatients get diagnosedwith it, and the conceptsaturates the psychiatricand popular culture.Generalized anxietydisorder, a diseaseconceived over a boozydinnerandwrittenintotheDSMwithafairlyarbitrarysetofcriteria,hasnowhadthousands of studies

appliedto it,andtheFDAhas approved multipledrugs for treating it. Butwhat if, as Sheehancontends, there is no suchthing as generalizedanxiety disorder—at leastnot as a disease distinctfrom panic disorder ormajor depression?‖ IfSheehan is right, a largeedifice of diagnosis,prescription,andacademic

study has been built uponsomething—generalizedanxiety disorder—that ispresumed to exist innaturebutthatinfactdoesnot.

[At current rates ofValium use], thearrival of themillennium wouldcoincide with the totaltranquilization of

America.—“BENZODIAZEPINES:USE,OVERUSE,MISUSE,

ABUSE,”EDITORIALINTHELANCET(MAY19,1973)

Even as Thorazineemptied the asylums andantidepressantprescriptions grewexponentially through thelate 1950s, nothing

approached the runawaycommercial success ofMiltown. Hence theinstructions given to LeoSternbach, a chemist atHoffmann–La Roche inNewJersey:“Inventanewtranquilizer,” his bossestold him. So Sternbachthought back to researchhe had done onheptoxdiazine-based dyeswhile a postdoctoral

student in Poland in the1930s. What wouldhappen if he chemicallymodifiedthemalittle?Hetested more than fortydifferent variations onanimals—butnoneseemedto have a tranquilizingeffect.Hoffmann–LaRocheabandoned the project.Sternbach was reassignedtoworkonantibiotics.But one day in April

1957, a research assistantwho was cleaningSternbach’s lab cameacross a powder (officialname: R0-5-090) that hadbeen synthesized a yearearlier but was nevertested. Without hope, asSternbach said later, hesent it over to the animaltestersonMay7,hisforty-ninth birthday. “Wethought that the expected

negative result wouldcomplete our work withthis series of compoundsand yield at least somepublishablematerial.Littledidweknowthatthiswasthe start of a programwhichwouldkeepusbusyformanyyears.”Happy birthday.

Sternbach had, mostly byaccident and nearlywithout realizing it,

invented the firstbenzodiazepine:chlordiazepoxide, whichwould be given the tradename Librium (derivedfrom “equilibrium”) andwas the forerunner ofValium, Ativan, Klonopin,and Xanax, the dominantantianxietymedications ofour age. Because of anerror in his chemicalprocess, R0-5-090 had a

molecular structuredifferent from the otherforty compoundsSternbachhadsynthesized.(It had a benzene ring ofsix carbon atomsconnected to a diazepinering of five carbon atomsand two nitrogen atoms—thus “benzodiazepine.”)The director ofpharmacological researchat Hoffmann–La Roche

tested the new substanceon cats and mice anddiscovered,tohissurprise,that although it was tentimes more potent thanMiltown,itdidnotnotablyimpair the animals’ motorfunction. Time reportedthat keepers at the SanDiego Zoo had tamed awild lynxwith Librium.Anewspaper headlineblared: “The Drug That

Tames Tigers—What WillIt Do for NervousWomen?”To gaugechlordiazepoxide’s toxicityto humans, Sternbachperformedthe first testonhimself. He reportedfeeling“slightlysoftintheknees” and a little bitdrowsy for a few hours,but otherwise heexperienced no ill effects.

By the time the FDAapproved the drug, onFebruary 24, 1960,Librium had already beenadministered to sometwenty thousand people.The early reports in themedical journals ravedabout its effectiveness.Patients who hadpreviouslyfoundthatonlyelectroshocktherapycouldcontrol their anxiety

declared that Libriumwasequally or more effective.A study published in TheJournal of the AmericanMedical Association inJanuary 1960 reportedthatwhen212outpatientsinNewJerseywitharangeof psychiatric ailmentswere given Librium, 88percent of those with“free-floating anxiety”received some degree of

relief.Theresearchersalsofound that the drug waseffective in treating“phobic reactions,”“compulsions” (what wewould today labelobsessive-compulsivedisorder), and “tension.”The lead researcher of aseparate study proclaimedthe development ofLibrium to be “the mostsignificantadvancetodate

in thepsychopharmaceuticaltreatment of anxietystates.”Thedrugwasshippedto

American pharmacies inMarch 1960. The firstHoffmann–La Rocheadvertisement for Libriumsaid it was for “thetreatment of commonanxieties and tension.”Withinthreemonths,sales

ofLibriumwereoutpacingsales of Miltown; by theend of the decade, moreprescriptions had beenwritten for Librium thanfor any other medicationon earth. Physiciansprescribed it foreverything fromhangovers, upsetstomachs, and musclespasms to all varieties of“tension,” “nerves,”

“neurosis,” and “anxiety.”(One doctor noted thatLibrium had the samerange of indications asgin.)Librium remained themost prescribed drug inAmericauntil1969—whenit was displaced byanother compoundsynthesized by LeoSternbach, this one withthe mellifluous chemical

name 7-chloro-1, 3-dihydro-1-methyl-5-phenyl-2H-1, 4-benzodiazepin-2-one. ThisnewdruglackedLibrium’sbitter aftertaste, andstudies found it to be twoandahalftimesaspotent.Themarketingdepartmentat Hoffman–La Rochedubbed it Valium (fromthe Latin valere, “to farewell” or “to be healthy”),

and Valium, in turn,remained America’s mostpopular drug until 1982.aIn 1973, Valium becamethefirstdrugintheUnitedStates to exceed $230millioninsales(morethan$1 billion in today’sdollars)—even as itspredecessor, Librium,continued to remainamong the five mostprescribed drugs in the

country. In 1975, it wasestimated that one ineveryfivewomenandonein every thirteen men inAmerica had takenLibrium, Valium, or someotherbenzodiazepine.Onestudy found that 18percent of all Americanphysicians were regularlytaking tranquilizers in the1970s. Advertisements forthe drugs became

ubiquitous in the medicaljournals. “It is ten yearssince Librium becameavailable,”wentthetextofa typical Libriumadvertisement from the1970s. “Ten anxious yearsof aggravation anddemonstration, Cuba andVietnam,assassinationanda devaluation, Biafra andCzechoslovakia. Tenturbulent years in which

the world-wide climate ofanxietyandaggressionhasgiven Librium—with itsspecificcalmingactionandits remarkable safetymargin—auniqueandstillgrowing role in helpingmankind to meet thechallenge of a changingworld.”By the end of thedecade, Librium andValium had made

Hoffman–La Roche—“thehouse that Leobuilt”—thebiggest pharmaceuticalcompanyintheworld.Thebenzodiazepines hadbecome the greatestcommercial success in thehistory of prescriptiondrugs.But as benzodiazepinesales grew through the1960s and 1970s, so didthebacklashagainstthem.

Some doctorswarned thatthe drugs were beingoverprescribed. In 1973,Leo Hollister, apsychiatrist at Stanford,mused, “Whether theincrease [in the use ofantianxiety agents] is theresult of the generallyturbulent times whichhave prevailed in the pastdecade,ortheintroductionof new drugs and their

widespread promotion, orof sloppy prescribingpractices of physicians isuncertain.” (If 18 percentofdoctorswerethemselvestaking Valium, that mightaccount for some of thesloppiness.)By the middle of the

1970s, the FDA hadcollectednumerousreportsof benzodiazepinedependence.Manypatients

who had been on highdosages of Valium orLibriumforlongperiodsoftime would experienceexcruciating physical andpsychological symptomswhen they stopped takingthe medication: anxiety,insomnia, headaches,tremors, blurred vision,ringing in the ears, thefeeling that insects werecrawling all over them,

and extreme depression—and, in some cases,seizures, convulsions,hallucinations, andparanoiddelusions.Bythetime Ted Kennedy led the1979 Senate hearings onthe hazards ofbenzodiazepines, criticshad a rich literature ofhorror stories to draw on.Judy Garland’s death,among others, was

attributed to a toxiccombination ofbenzodiazepines andalcohol. Fears aboutbenzodiazepines weregiven a broad airing byBarbara Gordon, a startelevision writer at CBSwho had been nearlydestroyed by addiction toValium. Gordon’sexperience withbenzodiazepine

dependence, as recountedinhermemoir,I’mDancingasFastas ICan,resonatedwidely. The book becamea New York Times bestseller in 1979 and afeature film starring JillClayburgh in 1982. Thatwas the year PublicCitizen, the organizationled by the consumeradvocate Ralph Nader,publishedStopping Valium,

which alleged rampantbenzodiazepineaddiction.Social critics worried

that the rampantprescriptionofValiumwaspapering over the roughedges of society,medicating awayradicalism, dissent, andcreativity. “One mustconsider the broaderimplicationsofacultureinwhich tens of millions of

adult citizens have cometo use psychoactive drugsto alter virtually everyfacet of theirwaking (andsleeping) behavior,”warned one doctor at a1971 academic conferenceon drug use. “What doesthat say about the impactof modern technology onour style of life? Whatchanges may be evolvingin our value system?”b

Marxist intellectuals likeHerbertMarcuseattributedwidespreadpillpoppingtocapitalist alienation.Conspiracy theoristsinvoked Aldous Huxley’sdystopian Brave NewWorld, alleging that thegovernment was exertingsocial control bytranquilizing the masses(whichwas ironicbecauseHuxley himself was an

enthusiastic promoter oftranquilizers). An editorialpublished in theprestigious BritishmedicaljournalTheLancet in1973frettedthatatcurrentratesofValiumuse,whichuptothat point had beengrowingat a clipof sevenmillion prescriptions ayear, “the arrival of themillennium wouldcoincide with the total

tranquilization ofAmerica.”cThe looming expirationofValium’spatentin1985helped spur the rise of anew benzodiazepine,alprazolam, which theUpjohn Company releasedwiththetradenameXanaxin 1981. Entering themarketjustaftertheDSM-III had introduced anxietydisorders as a clinical

category,Xanaxgotahugecommercial boost frombeing the first drugspecifically approved bythe FDA for the treatmentofthenewlycreatedpanicdisorder.dMany patients—and

before long I was one ofthem—found that Xanaxcutdownonpanicattacksand reduced physicalsymptoms like dizziness,

palpitations, andgastrointestinaldistress,aswell aspsychological oneslikeexcessive timidityandfeelings of dread. (ThepoetMarieHoweoncetolda friend ofminewhowasafraid to fly after 9/11:“Youknowthat littledoorinyourbrainmarkedFear?Xanaxclosesit.”)By1986,Xanax had overtakenMiltown, Librium, and

Valium to become thebest-selling drug inhistory. It has dominatedthe tranquilizer marketeversince.e

Anxiety and tensionseem to abound in ourmoderncultureandthecurrent trend is toescape theunpleasantness of itsimpact. But when has

life ever been exemptfromstress?Inthelongrun, is itdesirable thata population be everfree from tension?Should there be a pillfor every mood andoccasion?—FROMADECEMBER1956REPORTBYTHENEWYORKACADEMYOFMEDICINE

Benzodiazepines havebeen a leadingpharmaceutical treatmentfor anxiety for more thanhalf a century. But notuntilthelate1970sdidtheItalian neuroscientistErminio Costa—yetanother veteran of SteveBrodie’s lab at theNational Institutes ofHealth—finallyhomeinontheir salient chemical

mechanism:theireffectona neurotransmitter calledgamma-aminobutyric acid,or GABA, which inhibitsthe rate at which neuronsfire.Some brief and

oversimplifiedneuroscience: Aneurotransmitter calledglutamateexcitesneurons,causing them to firemorerapidly; GABA, on the

other hand, inhibitsneurons, slowing theirfiring and calming brainactivity. (If glutamate isthemainacceleratorofthebrain circuitry, GABA isthe main brake.) Costadiscovered thatbenzodiazepines bind toGABA receptors found onevery neuron, amplifyingGABA’s inhibitory effectsandsuppressingactivityof

the central nervoussystem. In binding to theGABA receptors,benzodiazepines changethe receptors’ molecularstructure in a way thatcauses theGABA signal tolast longer, which in turncauses the neuron tocontinue firing at a lowerrate, calming brainactivity.Knowing even this

superficial bit ofneurosciencehasgivenmeaserviceablemetaphorforunderstanding how mybrainproducesanxietyandhow Xanax reduces it.Whenmy anxietymounts,my autonomic nervoussystem gets kicked intofight-or-flight mode, mythoughtsstartracing,andIstartimaginingallkindsofcatastrophic things; my

body feels like it’s goinghaywire. I imagine thefiring of my synapsesgetting faster and faster,likeanoverheatingengine.I take aXanax, and aboutthirtyminutes later, if I’mlucky,IcanalmostfeeltheGABA system putting onthe brakes as thebenzodiazepines bind totheir receptors and inhibitneuronal firing.

Everything…slows…down.Of course, this is a

rather reductionistmetaphor.Canmyanxietyreally be boiled down tohow effectively gated mychloride ion channels areortothespeedofneuronalfiring in my amygdala?Well, yes, at some level itcan. Rates of neuronalfiring in the amygdalacorrelate quite directly

withthefeltexperienceofanxiety.Buttosaythatmyanxiety is reducible to theions inmyamygdala is aslimiting as saying thatmypersonality or my soul isreducible to themoleculesthat make up my braincells or to the genes thatunderwrotethem.In any case, I have amore practical concern:What is this long-term

reliance onbenzodiazepines doing tomy brain? By this point, Ihave takenbenzodiazepines (Valium,Klonopin, Ativan, Xanax)at varying doses andfrequencies for more thanthirty years. For severalyears during that time, Ihavebeenontranquilizersaround the clock formonthsatatime.

“Valium, Librium, andother drugs of that classcausedamagetothebrain.Ihaveseendamagetothecerebral cortex that Ibelieveisduetotheuseofthese drugs, and I ambeginningtowonderifthedamage is permanent,”DavidKnott,aphysicianatthe University ofTennessee,warnedbackin1976.Inthethreedecades

since then, scores ofarticles in scientificjournals have reported onthe cognitive impairmentobserved in long-termbenzodiazepine users. A1984 study by MalcolmLader found that thebrainsofpeoplewho tooktranquilizers for a longtime physically shrank.(Subsequent studies haveshown that different

benzodiazepines seem toconcentrate the shrinkagein different parts of thebrain.) Does this explainwhy at the age of forty-four, after several decadesof intermittentlycontinuous tranquilizerconsumption, I feelstupiderthanIusedto?

* I’ve just listed tenof the thirteen

DSM criteria for a panic attack;the other three symptoms arefeelings of depersonalization orunreality,fearoflosingcontrolorgoingcrazy,andfearofdying.Atleast four of these thirteensymptoms must be present for apanic attack to have occurred,accordingtotheDSM.

† Another way of characterizingthiswas as a victory of the neo-KraepeliniansovertheFreudians.Many scholars consider Emil

Kraepelin,notSigmundFreud,tobe the crucial figure in thehistory of psychiatry.Psychoanalysis, these scholarssay, was just a blip; Kraepelin’ssystem of disease classificationboth predated Freudianism andoutlastedit.

In 1890, when Freud wassettinguphispractice inVienna,Kraepelin,thenathirty-four-year-old physician, took aprofessorship in psychiatry at

Heidelberg University. Whilethere, Kraepelin becameinterested in the symptoms ofvarious mental illnesses. He andhis residents would draw up anote card for each patient whoentered his clinic at Heidelbergandwouldrecordonitsymptomsandapreliminarydiagnosis.Eachcardwouldthenbeplacedinthe“diagnosis box.” Every time anew symptom appeared, andevery time a diagnosis was

revised, the patient’s cardwouldbe taken from the box andupdated. When the patient wasreleasedfromthehospital,hisorher disposition and finaldiagnosis would be recorded.Over the years, Kraepelinaccumulated many hundreds ofsuch cards,whichhewould takeon vacation to study. “In thismanner we were able to get anoverview and see whichdiagnoseshadbeenincorrectand

thereasonsthathadledustothisfalseconception,”hewrote.

This systematic recording ofpatient symptoms and diagnosesmaynotseemnoveltoday,butnoonehadattempted toapply suchthorough observation andclassification to mental illnessbefore Kraepelin. (Actually, oneexception here was astrologers.Through the Enlightenment,astrologers kept meticulousmedical records so they could

chart symptoms againstastrological alignments, lookingfor correlations that would beusefultotheminfuturediagnosesand treatments. This recordkeeping may in fact have madeastrologers better able toprognosticate the course ofdiseases than doctors,who actedon intuition rather thansystematic observation.Astrologers, in otherwords,mayhavebeenmorelikelytoprovide

evidence-based medicine thandoctors were.) Diagnoses werehaphazard and random.Kraepelin’s goal in gathering allthis data was to try to cleavenature at the joints—to identifythe cluster of symptoms thatcharacterizedeachmentaldiseaseand toproject theirdevelopmentoverthelifecourse.UnlikeFreud(who was ambiguous aboutwhether mental illness was amedicaldiseaseorapsychosocial

problem of “adjustment”),Kraepelin came to believestrongly that psychiatry was asubfield of medicine. Emotionaldisorderswere biological entitiesthat could be identified anddifferentiated the way measlesandtuberculosiswere.

Kraepelin used the symptomdataheaccumulatedonhiscardsas the basis of the psychiatrytextbook he published in 1883.Revised multiple times over the

years, his Compendium derPsychiatrie came to be the mostinfluential psychiatric textbookeverpublished.Bythetimeofthesixth edition in 1899, it hadbecome the urtext of psychiatricclassification.

Even through themiddleyearsof the twentieth century, whenpsychoanalysis pushedKraepelin’s biological psychiatryto the margins, the Kraepelinianand Freudian systems of disease

classificationexistedsidebyside.When the first edition of theDiagnostic and Statistical Manualwaspublishedin1952,itdivideddiseases into different illnesscategories based on symptomclusters, very much the wayKraepelin’s nineteenth-centurytextbooks had. But theterminology that described mostof those illnesses waspsychoanalytic, so almosteverything in the first two

editions of the DSM blendedtogether into a soup of medicaland psychoanalyticnomenclature.

‡ I will say more about this inchapter7.

§ The distinction between, say,generalized anxiety disorder andpanicdisorderliesnotinhowthedisease is acquired—whether bygenes or childhood trauma orunreleased libido—but onwhether a person experiences a

certain minimum number ofsymptomsfromachecklist.

‖ Recall from chapter2 that somegeneticresearchsuggeststhereisin fact no meaningful differencebetween depression andgeneralizedanxietydisorder.

a Sternbach would also developflurazepam (marketed asDalmane) and clonazepam(marketed as Klonopin).Klonopin, like Valium, is stillfrequently prescribed today as a

long-actingbenzodiazepine.

bFeministshadrelatedconcerns.AseriesofadsrunbyRocheintheearly 1970s presumed to offer atreatment for spinsterhood: “35,single and psychoneurotic,”began a typical full-pageadvertisement, this one tellingthe sad story of Jan. “Youprobably see many … Jans inyour practice,” the ad went on.“The unmarrieds with low self-esteem.Janneverfoundamanto

measure up to her father. Nowshe realizes she’s in a losingpattern—and that shemay nevermarry.”Thecure?Valium.(“Youwakeupinthemorning,andyoufeelasifthere’snopointingoingon another day like this,” BettyFriedan had written in 1963 inThe Feminine Mystique. “So youtake a tranquilizer because itmakesyounotcaresomuchthatit’spointless.”)

c As it turned out, Valium use

peakedin1973.

d This approval was not withoutcontroversy. The first favorablestudiesofXanax’seffectonpanicwerepublishedintheArchives ofGeneral Psychiatry, whose editorat the time, Daniel Freedman,turned out to be on Upjohn’spayroll as a member of itsDivision of Medical Affairs.Critics said this had undulybiased him and that the studiesshould not have been published

because they were poorlyconstructedandthereforedidnotactually demonstrate that thedrugwaseffective.

e In 2010, Xanax was the twelfthmost commonly prescribed drugin America and the mostfrequently prescribedpsychotropic medication—morewidelyprescribed thanProzacoranyothersingleantidepressant.

CHAPTER7

MedicationandtheMeaningofAnxiety

When Valium camealong, both patientsand their doctors were

willing to define theirproblems in terms ofanxiety.… WhenProzac, a drug fordepression, arrived onthe scene, the accentfell on depression asthe hallmark ofdistress.—EDWARDSHORTER,AHistoryofPsychiatry

(1997)

Inthespringof1997,aftera difficult year—myparents’ divorce, anunhappy job situation, abad romance—and somemonths off psychiatricmedications, I began, atmy therapist’s urging, totake Paxil, an SSRIwhosegeneric name isparoxetine.After a week or so on

Paxil, I experienced an

infusion of energy thatborderedonmanic: Isleptfewerandfewerhours,butwithout feeling tiredduringtheday;Icould,forthe first time in my life,regularly awake in themorning feeling energetic.The mild mania passed,but what followed was aslow brightening of mymood. I ended—finally,after several unsuccessful

attempts—mycodependent anddysfunctional relationshipwith my girlfriend ofnearly two years. I got apromotion at the smallmagazine where I wasworking.Istarteddating.Atsomepointthatfall,I

realized I had notexperienced a full-blownpanic attack since I’dstartedonPaxil inApril—

by far my longest suchstretch since middleschool. Iwas experiencingless anxiety, feelingproductiveandengagedinmywork,andenjoyinganactive social life. Mystomach settled. Paxilwasmagic.Orwasit?Becausewhat

was cause and what waseffect? That promotion Igot at work came along

after someone left and Iwas elevated to fill theposition; thatwould likelyhave happened even if Ihadn’t gone on Paxil.Maybe that small boost inmy professional status,along with the moreinteresting andempowering day-to-dayresponsibilities of the job,bolstered my self-esteem,whichinturngavemethe

confidencetostartsendingout freelancework,whichin turn made me feelprofessionally engaged.And while I felt like thePaxil had somehow givenme the strength to finallybreakthestubborncordofneurotic codependencethat had tied me to mygirlfriend, maybe I wouldhave done that anyway—and there is no question

that, Paxil or no Paxil,being out of thatrelationship wasliberating. (For her, too,I’m sure; we haven’tspokensince.)Somaybeitwas the particularconstellationofeventsthatcame together that spring—the promotion, thebreaking off of adysfunctional relationship,the end of a dark Boston

winter and the arrival ofspring—that lifted myanxiety and depression.Maybe Paxil had nothingtodowithit.But I think it did.

Beginning with that briefmanic boost, my livedexperience felt like it wasPaxil inflected—andInowknow that my clinicaltrajectory (mild mania,lifting of mood, effecting

ofpositive life changes) isa fairly common one. Ofcourse, another possibilityisthatwhatIenjoyedthatspring and summer wasthe placebo effect—thePaxil worked because Ibelieved it would work.(With the placebo effect,the power of belief itself,rather than the chemicalcontentofanymedication,isthesalientmechanism.)

But the Paxil was notmagic—or if it was, itsmagic ran out. Becauseafter trundling merrilyalong in medicatedcontentment for tenmonths, my short-livedfeeling of invulnerabilitywas punctured within aperiodoftenminutes.In those firstmonthson

Paxil, I had—for the firsttime in twenty years—

been able to flywith onlymoderate anxiety. So oneFebruarymorning, IdroveheedlesslythroughafierceNewEngland rainstorm tothe airport (how nice notto be in a nervous swivetfordaysbeforeeveryplaneride!), boarded my flight,and settled in with mynewspaper for the hour-long trip to Washington,D.C. I can’t say that Iwas

ever, even in thoseglorious early days onPaxil, free of flyinganxiety. But it was agentler experience,manifesting itself asbutterflies inmy stomach,sweatonmypalms,andamild feeling ofapprehension—what Iimagine many people feelupon takeoff. So there Isat,twenty-eightyearsold,

feeling relativelycompetent and grown-up(Here I am, I thought, theexecutive editor of amagazine, flying toWashington on business,reading my New YorkTimes), confidentlyinsulated from terror bymy morning dose oftwentymilligramsofPaxil,that little pink pill thathadkeptmepanic-freefor

a blissful few months, aswetaxiedandtookoff.And then, passing

through the dark cloudsthat were producing therainstorm below, we ranintoturbulence.It lasted all of ten

minutes. Fifteen at most.But the whole time I wasconvinced we were goingtocrash—or,worse, that Iwould get airsick and

throwup.Handsshaking,Igulped two Dramamine.Beverageservicehadbeensuspended—the flightattendantshadbeenaskedto stay seated, whichterrified me. But as Ilooked around the cabin,none of my fellowpassengers seemed undulyperturbed. To my left, aman tried to read hisnewspaper, despite the

thrashing and dipping ofthe plane; to my right,across the aisle, a womanappeared to doze. I,meanwhile, wanted toscream. I desperatelywanted the turbulence toend (Please, God, pleasemake it end now and I’llbelieve in you and be goodand pious forever) and theDramamine to take effect,and I craved, above all,

unconsciousness,anendtothemisery.Of course, my fears of

crashing must not havebeen completelyconsuming,because Ihad,even in that moment, anadditional worry:Wasmypanic so obvious that theotherpassengerswouldseeit? Logically, one anxietyshould have canceled outthe other: if we were all

going to die, I shouldn’thave been worried aboutan ephemeral moment ofearthly embarrassmentbefore plunging intoeternaloblivion,right?Onthe other hand, if I wasgoing to end upembarrassed after theflight,thatwouldmeanweweren’tgoingtodie,right?Andatthatmoment,tobesafely on the ground and

tonotbedead—nomatterhow embarrassed—was acondition greatly to bedesired. But in myamygdala-controlledbrain,with my sympatheticnervous system on fullalert, there was no roomfor such clarity of logic.All I could think was, I’mgoing to throw up and I’mgoing to be humiliated andI’m going to die and I’m

terrifiedandall Iwant is tobe out of this situation andnever to get on a planeagain.Then we passed above

the clouds, and there wasclear sky and sun outsidethe window, and the ridewas completely smooth.The seat belt sign wasturned off. Beverageservice resumed. Myparasympathetic nervous

systemkickedin,arrestingthe firing rate of thehyperactiveneuronsinmyturbocharged amygdala,andI sank intoarelieved,Dramamine-enhancedexhaustion. Half an houror so later, we landeduneventfully inWashington.But the Paxil had

stoppedworking.Not completely, at least

not right away. But theillusion of beingsurrounded by aninvincible anxiety-repelling Paxil force fieldhadbeendispelled.This, Inow know, is not aninfrequent occurrence.Certain SSRI medicationscanreduceanxietyandcutdown on panic attacks—butaccordingtothestress-diathesis model of panic,

strong stimuli (like aturbulentflight)arepotentenough to break througheven medication-adjustedbrainchemistrytoproduceintense anxiety. And thiscan be, because of theeffect the breakthroughhasonthethinking(orthe“cognitions”) of theindividual, like a magicalspell being broken. (Othertimes, certain drugs just

stopworkingwithoutsuchstressful provocation; thisphenomenon has beencalled “the Prozac poop-out.”)After that day, my

general anxiety levelslowly rose again. Mypanic attacks began torecur—mild andinfrequent at first, thenmore severe and moreoften. My flying phobia

resurged—Ineededtotakea large dose of Xanax orKlonopin or Ativan beforegetting on any flight, andsometimes even thatwasn’tenough.OnmyfirstairplanetripwithSusanna,who was later to becomemywife,myanxietygotsobadsoonaftertakeoffthatI began shaking andgasping frantically, andthen,asSusannalookedon

in bewilderment, mystomach cramped and Ilost control ofmy bowels.I had planned the trip—threedaysinLondon—asaromantic vacation, anattempt to woo andimpress her. This was nota good start. Nor was therest of the trip muchbetter: those parts of thevacation that I did notspend sedated into near

catatonia by massivequantitiesofXanaxIspentquakinginmortaldreadofthereturnflight.

I kept taking Paxil forseveralyears,evenafter ithadlost itspanic-repellingmagic, out of acombinationofinertiaandthe fear of what mighthappenifIstopped.Butby

the spring of 2003, I hadbeenonPaxilforsixyears,and my anxiety was onceagaininfullbloom.Itwastimetotrysomethingnew.This is what prompted

metoseeDr.Harvard,thepsychopharmacologist.During my first visit, hewastakingmycasehistorywhen,asiftodemonstratemydisorder,Ihadafloridpanic attack that rendered

me breathless and tearful,unable to continue. “Takeyour time,” Dr. Harvardsaid. “Continue whenyou’re ready.” Whether itwas the facts of my casehistoryor the vividness ofthe panic attack Iunwillingly displayed forhim, Dr. Harvard seemedsurprised to learn that Ihad gone completelyunmedicated for stretches

of my life. He seemedamazed. To him, I was ahard case, not equippedfor normal humanfunctioning withoutpharmaceuticalassistance.We discussed thepharmacological options,eventually settling onEffexor,thetradenameforvenlaxafine, a serotonin-norepinephrine reuptakeinhibitor (SNRI), which

impedes the absorption—and therefore boosts theintrasynaptic levels of—both serotonin andnorepinephrine in thebrain. We talked abouthowtotaperslowlyoffthePaxil, which I did,carefully following hisinstructions, decreasingthe dosage bit by tiny bitover a period of severalweeks.

Over the years, I hadfrom time to timeconsidered trying to weanmyself off psychiatricmedication completely.After all, I reasoned, I’mpretty anxious onmedication—how muchworsecan Ibeoffof it? Soonce I finally did manageto taper most of the wayoff the Paxil, I thought,Whynot,let’stryflyingsolo

forawhile—nomoredrugs.I stopped taking the Paxiland didn’t start theEffexor.Here is what you don’t

see in those TV andmagazine advertisementsfor psychotropic drugs oreven, with any realspecificity or sympatheticunderstanding, in theclinical literature: the hellof going off them. I’ve

never taken heroin, so Ican’t say whether this istrue(Isuspectitisn’t),butmany people claim thatwithdrawal from Paxil isasbadaswithdrawalfromheroin. The headaches.The exhaustion. Thenausea and stomachcramps.Theknee-bucklingvertigo. The electriczapping sensation in yourbrain—a weird but

commonsymptom.And,ofcourse, the surge ofanxiety: waking up atdawn every morning to apounding heart andterrible dread; multiplepanicattacksdaily.Despitemydesire to tryto “be myself” andfunction withoutpharmacologicalassistancefor the first time in sixyears, I couldn’t hack it,

and so one morning afterbarely a week off thePaxil, I tookmy first doseofEffexor.Withinminutes,literally,Ifeltmuchbetter:the physical symptomsreceded;my state ofmindimproved.This cannot actuallyhave been due to theEffexor’s therapeuticaction—SSRIs and SNRIsgenerally need several

weeks to build up in thesynapses enough to startworking. More likely,something in the Effexorsomehow alleviated theeffects of chemicalwithdrawalfromPaxil.Butwhat is cause andwhat iseffect?Weretheemotionalanxiety and physicalmiseryIfeltaftergoingoffthe Paxil really the effectof chemical withdrawal?

Orwasthissimplywhatitfeels like to be meundrugged?Afterall,Ihadbeen on psychiatricmedication for longenough that maybe I hadforgottenwhatitfeelsliketoliveinmynakedbrain.Or was my misery thatspringlesstheresultofill-fated drug-switchingexperiments than of thestress in my life? Two

datesloomedattheendofthatsummer.Thefirstwasthe deadline for thedeliveryof themanuscriptofmyfirstbook,whichbythenhadbeeningestationfor six years (roughly thelengthof time I’dbeenonPaxil) and had endured aharrowing journey—fromeditor to editor andpublishing house topublishing house, through

the descent intoAlzheimer’s of mybiography’s subject andthe increasingly intrusiveinvolvement of mysubject’s powerful family—toget to thispoint.Theother was my wife’s duedateforthedeliveryofourfirst child.* Of thedifficulties I endured thatsummer, it’shard toknowexactly which were a

response to externalstressors and which weredrug related.Andof thosedrug-related difficulties,it’s hard to know whichwere withdrawal effectsfromdrugs Iwasweaningoff and which were sideeffects from drugs I wasgoingon.The contrast between

what the pharmaceuticalindustry’s promotional

materials and the clinicalresearch papers (many ofthem subsidized by grantsfrom the pharmaceuticalindustry)sayandwhattheroilingonlinecommunitiesof actual patients say islarge. I believe both sidesare generally honest andaccurate as far as they go(the drugs can havemeasurable therapeuticbenefits; the side effects

andwithdrawal symptomscanbe awful), butneitherone iswholly trustworthy.The drug companies, andthe doctors subsidized bythem, have a profit-motivated interest inpushing pills; the drugtakers are prettymuch bydefinitionanunhappyandunstablebunchprone, likeme,tobeingeasilythrownby physical symptoms.

Studies have shown thatpeople who score high onscalesofanxietysensitivitytend to suffer drug sideeffects more severely. (Abunch of nonanxiouspeople who took an SSRIwould likely bemuch lessbothered by any sideeffects and wouldtherefore be less likely tocomplain about them inonline forums.) So the

antidrug rants of the pill-popping communitycannot be taken at facevalue any more than canthe assessment of sideeffects and withdrawalsymptoms in thesometimes boosterishclinicalliterature.Though the Effexoreased what seemed to bethe physical symptoms ofmywithdrawalfromPaxil,

my anxiety and panicpersisted—and thenincreased.WhenI toldDr.Harvard about this, hisresponse, as the responseof psychiatrists andpsychopharmacologists sooften tends to be, was,“We need to elevate yourdosage.” The quantity ofEffexor I was taking wasnot sufficient, he said, tocorrect the “chemical

imbalance” in myserotonergic andnoradrenergic systems. SoI went from taking thirty-seven and a halfmilligrams to seventy-fivemilligramsofEffexorthreetimesaday.At which point myanxietylevelsshotthroughtheroof.Atnight,Iwouldawaken in the grip of araging panic attack.

During the day, I washaving multiple panicattacks—and even when Iwasn’thavingone,Ifeltasthough I were about to.Never had I felt suchchronic, persistentagitation; I couldn’t stopmoving and twitching,couldn’tbearthefeelingofbeing in my own skin.(The clinical term for thisis “akathisia.”)

Glimmerings of suicidebegan twinkling at theedgeofmyconsciousness.I called Dr. Harvard. “I

can’ttakeit,”Itoldhim.“Ithinkmaybe I need to getoff the Effexor. I feel likeI’m going crazy.” “Youneedtogiveitmoretime,”hesaid.Andhegavemeaprescription for Xanax,which he said would takethe edge off my anxiety

while giving the Effexortimetowork.Prescribing abenzodiazepine (likeXanax) to overcome theanxiety produced when apatient starts taking anantidepressant SSRI orSNRI (like Effexor) hasbeen standard practicesince the late 1990s. Andinmycasethisworked—alittle, fora short time.My

anxietyrecededsomewhat,and the panic subsided,butonlyifIfaithfullytookmy Xanax around theclock.To work on my book, Ihad rented a decrepitofficeonthethirdfloorofa crummy building inBoston’sNorthEnd,andtohastenmy progress, I hadhired a research assistant,Kathy, who shared the

spacewithme. Kathywasan excellent researcherand,whenIwasn’t feelingpanicky, delightfulcompany. But I wasembarrassed about myanxiety and felt I had tohide it, which meantleaving when I felt paniccoming on. So I wasforever contriving errandsto get me out of theoffice.†

Yet again I called Dr.Harvard.Andyetagainhesaid, “You’re not at atherapeutic level of theEffexor yet. Let’s increasethe dosage.” So I startedtakingmoreEffexor,andafew days later my visionblurred and I couldn’turinate. I called Dr.Harvard, and for once hesounded alarmed. “Maybewe’dbettergetyouoffthe

Effexor,” he said. But I’dbeen traumatized by thewithdrawal symptoms I’dsuffered when I’d stoppedtaking Paxil, and I toldhim so. (Discontinuationsyndrome is now aclinically acknowledgedPaxil phenomenon.) “I’mgiving you a prescriptionforCelexa,”he said,usingthe brand name forcitalopram, another SSRI.

“Starttakingitrightaway,and continue taking theXanax.”I did, and within a day

my vision cleared andmyurine again flowed, whichwould seem to suggestthose problems had beenside effects of the drug.But they might not havebeen: the tendency ofanxiety sufferers to“somaticize”—to convert

their neuroses intophysical symptoms—means it’s possible myblurred vision andrecalcitrant bladder weresimply physicalrepresentations of myanxiety.The transition fromEffexor to Celexa wassmoother than thetransition from Paxil toEffexor had been, perhaps

because I didn’t wean offone before going on theother. But since then,despite chronic andintermittently severeanxiety, I’ve not gone adaywithouttakinganSSRIantidepressant, and I’venot adjusted my dosagemuch,forfearofrepeatingthe Paxil-to-Effexorexperience. At times Ithink wistfully about my

earlydaysonPaxil,whenIfoundamodicumofrelief,and wonder if I shouldn’tswitch back and try toachieve again that panic-free nirvana. But theclinical research is full ofpeoplewhoreturntodrugstheyhadtakenearlieronlyto find them no longereffective.And in any case, theexperience of weaning off

Paxil is not one Iwant torepeat.

Medication,medication,medication!What do Igottoshowforit?—THESOPRANOS’TONYSOPRANOTODR.MELFIAFTERAYEARONPROZACFORHISPANICATTACKS

Exploding into the

national consciousnesswith theMarch 26, 1990,edition of Newsweek,whose cover featured agreen-and-white capsulealongside the words “ABreakthrough Drug forDepression,” fluoxetine,under its trade nameProzac,wouldbecome theiconic antidepressant ofthe late twentieth century—a blockbuster for its

manufacturer, Eli Lilly.The first selectiveserotonin reuptakeinhibitor (SSRI) to bereleased in the UnitedStates, Prozac wouldbefore long surpass Xanaxas the best-sellingpsychotropic drug inhistory—even ascompeting SSRIs (amongthemZoloft,Paxil,Celexa,and Lexapro) would soon

be on their way tooutpacingProzac.With the possibleexception of antibiotics,SSRIs are the mostcommercially successfulclass of prescription drugsin history. By 2002,according toone estimate,some twenty-five millionAmericans—more than 5percentof allmenand11percent of all women—

were taking an SSRIantidepressant. Thenumbers have only grownsince then—a 2007estimateputthenumberofAmericans on SSRIs atthirty-three million. Thesedrugs dominate not onlyhospital psychiatry andourmedicine cabinets butalso our culture andnatural environment.Books like Prozac Nation,

ProzacDiary, andListeningto Prozac (and, of course,Talking Back to Prozac)populated the best-sellerliststhroughoutthe1990s,and Prozac and Lexaprojokes remain a fixture ofmovies and New Yorkercartoons. Trace elementsof Prozac, Paxil, Zoloft,and Celexa have beenfoundintheecosystemsofAmerican frogs (causing

them developmentaldelays and anomalies), inthe brains and livers offishinNorthTexas,andinLake Mead, America’slargest reservoir, whichsupplies drinkingwater toLas Vegas, Los Angeles,SanDiego,andPhoenix.Given how completelySSRIs have saturated ourculture and ourenvironment,youmightbe

surprised to learn that EliLilly, which held the U.S.patent for fluoxetine,killed the drug indevelopment seven timesbecause of unconvincingtest results. Afterexaminingtepidfluoxetinetrial outcomes, as well ascomplaints about thedrug’ssideeffects,Germanregulators in 1984concluded, “Considering

the benefit and the risk,we think this preparationtotally unsuitable for thetreatment of depression.”Early clinical trials ofanother SSRI, Paxil, werealsofailures.‡How did SSRIs go from

being consideredineffective tobeingoneofthe best-selling drugclasses in history? In theanswer to that question

lies a story about howdramatically ourunderstanding of anxietyand depression haschanged in a short periodoftime.Once again the storybegins at Steve Brodie’slaboratory at the NationalInstitutes of Health. AfterleavingBrodie’slabfortheUniversity of Gothenburgin Sweden in 1959, Arvid

Carlsson gave tricyclicantidepressants to micewith artificially depletedserotonin levels. Wouldthe antidepressants boostserotonin levels? Yes;imipraminehad serotonin-reuptake-inhibiting effects.In the 1960s, Carlssontried similar experimentswith antihistamines.Would they also inhibitthe reuptakeof serotonin?

Again,yes.Carlsson foundthat an antihistaminecalled chlorpheniraminehad a more powerful andprecise effect on thebrain’s serotonin receptorsthandideitherimipramineor amitriptyline, the twomostcommonlyprescribedtricyclics.Carlssoninvokedthis findingasevidence tosupportwhathecalledtheserotonin hypothesis of

depression. He then setabout applying thisdiscovery in pursuit of amore potentantidepressant. “This,” themedical historian EdwardShorter has written, “wasthe birthing hour of theSSRIs.”§Carlsson next

experimented with adifferent antihistamine,brompheniramine (the

active ingredient in thecough medicationDimetapp).It,too,blockedthe reuptake of serotoninand norepinephrine morerobustly than imipraminedid. He modified theantihistamine to createcompound H102-09,which blocked only thereuptake of serotonin.Working with a team ofresearchers at Astra, a

Swedish pharmaceuticalcompany,CarlssonappliedforapatentforH102-09—which had by then beenrenamed zimelidine—onApril 28, 1971. Earlyclinical trials suggestedzimelidine had someeffectiveness in reducingdepression, and in 1982Astra started selling it inEurope as theantidepressant Zelmid.

Astra licensed Zelmid’sNorth American rights toMerck, which beganpreparing to release thedrug in the United States.Then tragedystruck: somepatients taking Zelmidbecame paralyzed; a fewdied. Zelmid was pulledfrom pharmacy shelves inEurope and was neverdistributedinAmerica.Executives at Eli Lilly

watched thesedevelopments withinterest. Some ten yearsearlier, biochemists at thecompany’s labs in Indianahad fiddledwith chemicalderivatives of a differentantihistamine,diphenhydramine (theactive ingredient in theallergy medicationBenadryl), to create acompound called LY-

82816,whichhadapotenteffect on serotonin butonly a weak effect onnorepinephrinelevels.Thismade LY-82816 the most“clean,” or “selective,” oftheseveralcompoundstheresearchers tested.‖ DavidWong, an Eli Lillybiochemist, reformulatedLY-82816 into compoundLY-110140 and wrote uphis findings in the journal

Life Sciences in 1974. “Atthis point,” Wong wouldlater recall,“workon[LY-110140]was an academicexercise.” Nobody knewwhether therewould be amarket for even oneserotonin-boostingpsychiatric medication—and since Zelmid alreadyhadaheadstartofseveralyears in getting throughclinicaltrialsandontothe

market, Eli Lilly put LY-110140, now calledfluoxetine,aside.ButwhenZelmidstarted

paralyzingpeople,EliLillyexecutives realizedfluoxetine now had achancetobethefirstSSRIonthemarket inAmerica,so they restarted theresearch machinery.Thoughmany of the earlyclinical trials were not

notably successful, thedrug was approved andreleased in Belgium in1986. In January 1988,fluoxetine was released inthe United States,marketed as “the firsthighly specific, highlypotentblockerofserotoninuptake.” Eli Lilly gave itthe trade name Prozac,whichabrandingfirmhadthoughthad“zap”toit.

Twoyears later, thepillgraced the cover ofNewsweek. Three yearsafter that, Peter Kramer,the Brown psychiatrist,published Listening toProzac.WhenListening toProzaccameoutinthesummerof1993, I was twenty-threeand on my third tricyclicantidepressant—this timedesipramine, whose trade

nameisNorpramin.Ireadthe bookwith fascination,marveling at thetransformative effectsProzac had had onKramer’spatients.Manyofhispatientsbecame,asheput it, “better than well”:“Prozac seemed to givesocial confidence to thehabitually timid, to makethesensitivebrash,tolendthe introvert the social

skillsofasalesman.”Hmm,I thought. This soundspretty good. My longtimepsychiatrist, Dr. L., hadbeen suggesting Prozac tome for months. Butreading Kramer, I worriedabout what Faustianexchange was beingmadehere—what got lost, inselfhood or the moreidiosyncratic parts ofpersonality, when Prozac

medicated away thenervousness or themelancholy. In his book,Kramer concludedforcefully that for mostseverely anxious ordepressed patients, thebargain was worthwhile.Butheworried,too,aboutwhat he called “cosmeticpsychopharmacology”—the use of psychiatricdrugs by “normal” or

“healthy” people tobecome happier, moresocial,moreprofessionallyeffective.Beforelong,Ijoinedthemillions of otherAmericans taking SSRIs—and I’ve been on one oranother pretty muchcontinuously for going ontwenty years.Nevertheless, I can’t saywith complete conviction

that these drugs haveworked—or that they’vebeen worth the costs interms of money, sideeffects, drug-switchingtraumas, and who knowswhat long-term effects onmybrain.After the initial flush ofenthusiasm for SSRIs,someof the fears thathadsurroundedtranquilizersinthe1970sbeganclustering

aroundantidepressants.“Itisnowclear,”DavidHealy,the historian ofpsychopharmacology, haswritten, “that the rates atwhich withdrawalproblems have beenreportedon[Paxil]exceedthe rates at whichwithdrawalproblemshavebeenreportedonanyotherpsychotropicdrugever.”a“Paxil is truly

addictive,” Frank Berger,the inventor of Miltown,said not long before hisdeath in 2008. “If youhave somebody on Paxil,it’snot soeasy togethimoff.… This is not the casewith Librium, Valium andMiltown.”Afewyearsago,myprimarycarephysiciantold me she had stoppedprescribing Paxil becauseso many of her patients

had reported such severewithdrawaleffects.Even leaving aside

withdrawaleffects,thereisnow a large pile ofevidence suggesting—inline with those earlystudies of theineffectiveness of ProzacandPaxil—thatSSRIsmaynot work terribly well. InJanuary 2010, almostexactly twenty years after

introducing Americans toSSRIs,Newsweekpublisheda cover story reportingonstudies that suggestedthese drugs are barely aseffective as sugar pills forthe treatment of anxietyand depression. Twomassivestudiesfrom2006showed most patients donot get better takingantidepressants; onlyabout a third of the

patients in these studiesimproved dramaticallyafter a first trial. Afterreviewing dozens ofstudies on SSRIeffectiveness, the BritishMedical Journal concludedthat Prozac, Zoloft, Paxil,andtheotherdrugsintheSSRI class “do not have aclinically meaningfuladvantageoverplacebo.”bHow can this be? Tens

ofmillionsofAmericans—including me and manypeople I know—collectively consumebillionsofdollars’worthofSSRIs each year. Doesn’tthis suggest that thesedrugsareeffective?Not necessarily. At thevery least, these massiverates of SSRI consumptionhave not caused rates ofself-reported anxiety and

depression to go down—and in fact all this pillpoppingseemstocorrelatewith substantially higherrates of anxiety anddepression.“If you’re born around

World War I, in yourlifetime the prevalence ofdepression is about 1percent,” says MartinSeligman,apsychologistatthe University of

Pennsylvania. “If you’rebornaroundWorldWar IIthe lifetime prevalence ofdepressions seemed to beabout 5 percent. If youwere born starting in the1960s, the lifetimeprevalence seemed to bebetween10percentand15percent, and this is withlives incomplete”—meaning that in the endthe actual rates will be

higher. That’s at least atenfold increase in thediagnosis of depressionacross just twogenerations.The same trend is

evident inothercountries.InIceland,theincidenceofdepression nearly doubledbetween 1976 (before thearrivalofSSRIs)and2000.In1984, four years beforetheintroductionofProzac,

Britainreported38million“days of incapacity” (sickdays) resulting fromdepression and anxietydisorders; in 1999, after adecadeofwidespreadSSRIuse,Britainattributed117million days of incapacityto the same disorders—anincrease of 300 percent.Health surveys in theUnited States show thatthepercentageofworking-

age Americans whoreportedbeingdisabledbydepression tripled in the1990s. Here’s the moststriking statistic I’ve comeacross: Beforeantidepressants existed,some fifty to one hundredpeople per million werethought to suffer fromdepression;today,betweenone hundred thousand andtwo hundred thousand

people per million areestimated to havedepression.Inatimewhenwe have morebiochemicallysophisticated treatmentsthan ever for combatingdepression, that’s a 1,000percent increase in theincidenceofdepression.In his 2010 book,

Anatomy of an Epidemic,the journalist Robert

Whitaker marshaledevidence suggesting thatSSRIs actually causedepression and anxiety—that SSRI consumptionover the last twenty yearshas created organicchanges in the brains oftens of millions of drugtakers,making themmorelikely to feel nervous andunhappy. (Statistics fromthe World Health

Organization showing thattheworldwidesuicideratehasincreasedby60percentover the last forty-fiveyears would seem to giveweighttotheideathatthequotientofunhappinessinthe world has risen intandem with SSRIconsumption.) Whitaker’sargument about drugscausing mental illness iscontroversial—most

experts would dispute it,and it’s certainly notproven. What’s clear,though, is that theexplosion of SSRIprescriptions has caused adrastic expansion in thedefinitions of depressionand anxiety disorder (aswell as more widespreadacceptance of usingdepression and anxiety asexcuses for skipping

work), which has in turncaused the number ofpeople given thesediagnosestoincrease.

Wemaylookback150yearsfromnowandseeantidepressants as adangerous and sinisterexperiment.—JOSEPHGLENMULLEN,ProzacBacklash

(2001)

InAmerica,thequestionof when and whether toprescribe medications forroutine neurotic sufferingis bound up with twocompeting intellectualtraditions: our historicalrootsintheself-denialandasceticism of our Puritanforebears versus the post-baby-boom belief that

everyone is entitled to the“pursuit of happiness”enshrined in our foundingdocument. In modernpsychiatry, the tensionbetween these twotraditions plays out in thebattle between PeterKramer’s cosmeticpsychopharmacology andwhat’s known aspharmacologicalCalvinism.

Critics of cosmeticpsychopharmacology(including,tosomeextent,Kramer himself) worryaboutwhathappenswhenmillionsofmildlyneuroticpatients seek medicationtomakethemselves“betterthan well” and whencompetition to get andstay ahead in theworkplace creates apharmaceutical arms race.

The term“pharmacologicalCalvinism” was coined in1971byGeraldKlerman,aself-described “angrypsychiatrist” who was outto combat the emergingconsensus that if a drugmakes you feel good, itmust be bad. Life is hardand suffering is real,Klerman and his alliesargued, sowhy should ill-

founded Puritanism beallowed to interfere withnervous or unhappyAmericans’questforpeaceofmind?The pharmacologicalCalvinists believe that toescape psychic painwithout quest or struggleis to diminish the self orthe soul; it’s gettingsomething for nothing, aFaustian bargain at odds

with the Protestant workethic.“Psychotherapeutically,”Klerman wrotesardonically, “theworld isdivided into the first-classcitizens, the saints whocan achieve their cure orsalvation by willpower,insight, psychoanalysis orby behavior modification,andtherestofthepeople,who are weak in their

moral fiber and need acrutch.” Klerman angrilydismissed such concerns,wonderingwhywewould,out of some sense ofmisguided moralpropriety, deny anxious,depressedAmericansrelieffrom their suffering andthe opportunity to pursuehigher, more meaningfulgoals. Why remain miredin the debilitating self-

absorption of yourneuroses if a pill can freeyourmind?Americans are

ambivalent about all this.We pop tranquilizers andantidepressants by thebillions—yet at the sametime we have historicallyjudged reliance onpsychiatric medication tobe a sign of weakness ormoral failure.c A study

conducted by researchersattheNationalInstituteofMentalHealthintheearly1970s concluded that“Americans believetranquilizers are effectivebut have serious doubtsaboutthemoralityofusingthem.”Which sounds like a

somewhat illogical andself-contradictory position—butithappenstobethe

one I hold myself. Ireluctantly take bothtranquilizers andantidepressants, and Ibelievethattheywork—atleasta little,at leastsomeof the time. And Iacknowledgethat,asmanypsychiatrists andpsychopharmacologistshavetoldme,Imayhavea“medical condition” thatcauses my symptoms and

somehow “justifies” theuse of these medications.Yetatthesametime,Ialsobelieve (and Ibelieve thatsociety believes) that mynervous problems are insomewayacharacterissueoramoralfailing.Ibelievemyweak nervesmakemea coward and a wimp,with all the negativejudgment those wordsimply,whichiswhyIhave

tried to hide evidence ofthem—andwhichiswhyIworry that resorting todrugs to mitigate theseproblems both proves andintensifies my moralweakness.“Stop judging yourself!”Dr. W. says. “You’remaking your anxietyworse!”He’s right. And yet Ican’thelpconcurringwith

the 40 percent ofrespondents to that NIMHsurvey who agreed withthe statement “Moralweakness causes mentalillness and takingtranquilizers to correct oramelioratetheconditionisfurther evidence of thatweakness.”Of course, as we learn

more about how genesencode certain

temperamental traits anddispositions into ourpersonalities, it becomeshardertosustainthemoralweakness argument inquite thesameway. Ifmygeneshaveencoded inmean anxious physiology,how responsible can I beheld for the way that Iquiver in the face offrightening situations ortend to crumble under

stress? With the evidencefor a strong genetic basisto psychiatric disordersaccumulating,more recentsurveys about Americanattitudes toward relianceon psychiatric medicationreveal a dramatic shift ofopinion. In 1996, only 38percent of Americans sawdepression as a healthproblem—versus 62percent who saw

depression as evidence ofpersonal weakness. Adecade later, thosenumbers had more thanreversed: 72 percent sawdepression as a healthproblem, and only 28percentsawitasevidenceofpersonalweakness.

Theserotonintheoryofdepression iscomparable to the

masturbatory theory ofinsanity.—DAVIDHEALY,INA2002SPEECHATTHEINSTITUTEOFPSYCHIATRYIN

LONDON

Thedeeperonedigsintothe entwined histories ofanxiety andpsychopharmacology, theclearer it becomes that

anxiety has a direct andrelatively straightforwardbiological basis. Anxiety,likeallmentalstates,livesin the interstices of ourneurons, in the soup ofneurotransmitters thatbathesoursynapses.Relieffrom anxiety comes fromresetting our nervousthermostats by adjustingthe composition of thatsoup. Perhaps, as Peter

Kramermused in Listeningto Prozac, what ailedCamus’s stranger—hisanhedonia, his anomie—was merely a disorder ofserotonin.And then one digs a

littledeeperstillandnoneofthatisveryclearatall.Even as advances in

neuroscience andmolecular genetics haveallowedustogetmoreand

more precise in drawingconnections between thisprotein and that brainreceptor, or between thisneurotransmitter and thatemotion, some of theoriginal underpinnings ofbiological psychiatry havebeenunraveling.TheexaltationofProzac

a quarter century agocreatedacultof serotoninas the “happiness

neurotransmitter.” Butfrom the start, somestudieswerefailingtofinda statistically significantdifference between theserotonin levels ofdepressed andnondepressed people. Oneearly study of a group ofdepressed patients,reported in Science in1976,foundthatonlyhalfhad atypical levels of

serotonin—and only halfof those had serotoninlevelsthatwerelowerthanaverage, meaning thatonly a quarter of thedepressed patients couldbe considered serotonindeficient. In fact, anequally large number hadserotonin levels that werehigher than average.Manysubsequent studies haveproduced results that

complicate thenotionofaconsistent relationshipbetween serotonindeficiency and mentalillness.Evidently, thecorrelation betweenserotonin and anxiety ordepression is lessstraightforward than oncethought. None other thanthe fatherof theserotoninhypothesis of depression,

Arvid Carlsson, hasannounced that psychiatrymust relinquish it. In2002, at a conference inMontreal,hedeclaredthatwe must “abandon thesimplistic hypothesis” thata disordered emotion isthe result of “either anabnormally high orabnormallylowfunctionofa given neurotransmitter.”Not long ago, George

Ashcroft, who as aresearch psychiatrist inScotland in the1960swasone of the scientistsresponsible forpromulgatingthechemicalimbalance theory ofmental illness, renouncedthe theory when furtherresearch failed to supportit. In 1998, ElliotValenstein, aneuroscientist at the

University of Michigan,devoted a whole book,Blaming the Brain, toarguingthat“theevidencedoes not support any ofthebiochemicaltheoriesofmentalillness.”“Wehavehuntedforbig

simple neurochemicalexplanations forpsychological disorders,”Kenneth Kendler, theeditor in chief of

Psychological Medicine andaprofessorofpsychiatryatVirginia CommonwealthUniversity, conceded in2005, “and we have notfoundthem.”What if the reason wehaven’t been able topinpoint how Prozac andCelexa work is that, infact, they don’t work?“Psychiatricdrugsdomoreharm than good,” says

Peter Breggin, theHarvard-trainedpsychiatrist who is afrequent witness inlawsuits against the drugcompanies.He’sbackedupby those studies showingthat only about a third ofpatients get better onantidepressants.But studies havegenerally not found theresponse rates to other

forms of treatment to beall that much better. Andthe psychiatrists andpsychopharmacologists onthe front lines whoconsistently say that theyhave seen these drugswork time after timecannot all have beenfatally duped by the drugindustry’s marketingcampaigns. Sometimes thestatistical reality of the

randomized double-blindcontrolledstudiessaysonething while the clinicalreality (what psychiatristsand primary carephysicians observe in andhear from their patients)says another. What tomakeofallthis?I am willing to believe

that, for the most partanyway, both sides inthese debates are arguing

in good faith. Thepromedicationadvocates—the Gerald Klermans andFrank Bergers and PeterKramers and Dr. Harvardsof the world—have acompassionateHippocraticdesire to reduce theirpatients’ anxious sufferingwith drugs, and they aresincere in their desire todestigmatize anxietydisorders and clinical

depression by classifyingthemasmedicalproblems.The anti-medicationcrusaders—the PeterBregginsandDr.Stanfordsof the world—are sincerein their desire to protectpatients and would-beconsumers against whatthey believe to be theprofit-mindedrapaciousness of the drugcompanies and to help

patientsrecoverfromtheiranxiety on the strength oftheir own inner resources,rather than on potentiallydependency-inducingmedications.Ihave sympathy for themore reasonable drugindustry critics. I can saybased not only on thethousands of studies I’veporedoverbutonmyownlived experience that in

some ways the critics areclearly right—right aboutthe debilitating sideeffects, right aboutdependency andwithdrawal problems,righttoexpressskepticismaboutwhetherthesedrugswork as well as they’readvertised to, right toworry about what thelong-termeffectsofsuchaheavily medicated society

willbe.Butinsomeways,too, I believe, they arewrong. The drugs, manyother studies suggest, canwork—yes, only some ofthe time, in some people,withsometimesrottensideeffectsandbadwithdrawalsymptomsanddependencyproblems. And, yes, wedon’tknowwhatlong-termdamage they’re wreakingon our brains. And, yes,

the diagnostic categorieshave been artificiallyinflatedordistortedbythedrug companies and theinsurance industry. But Icantellyouwithhard-wonpersonal authority thatthere is legitimateunderlying emotionaldistresshere,whichcanbequite debilitating, andwhich these drugs canmitigate,sometimesonlya

little, sometimesprofoundly.When I talk to Dr. W.

about this, he reports thathisownclinicalexperiencecomportswithwhatIhavebeen finding in myresearch: there isenormous variability inhow different patientsrespondtodifferentdrugs.He once treated a patientwhose parents were

Holocaust survivors. Thiswoman was deeplydepressed; it was clear toDr. W. that she hadinternalized theirsurvivors’guilt,acommonphenomenon. He workedwithherformonthstogethertorecognizethis inaneffort to dispel herunhappiness. Nothinghelped; her devastatingdepression persisted week

afterweek.Then she triedProzac. After a fewweekson the drug, she came forher appointment one dayand said, “I feel great.” Afew weeks later, shedeemed herself cured andterminated treatment.ScoreonefortheSSRIs.But around that same

time, Dr. W. had anotherpatient, a man sufferingfrom obsessive-compulsive

disorder and low-gradedepression. That patient,too, started on Prozac—and within forty-eighthours was in the hospitalwith acute suicidalideation.ScoreoneagainsttheSSRIs.dDr. W. has a

psychopharmacologistcolleague with whom hehascollaborated foryears.Together they have

successfully treated manypatients with anxietydisorders. Whenever oneof their patients getsbetter, Dr. W. will say tothe psychopharmacologist,“Itwas clearly your drugsthat did it.” And he willrespond toDr.W., “No, itwas clearly yourpsychotherapythatdidit.”And then they laugh andcongratulateeachotheron

another successful case.But the truth is,asDr.W.acknowledges, they don’treally know what made agivenpatientrecover.

It is much cheaper totranquilize distraughthousewives living inisolation in tower-blocks with nowherefor their children toplay than to demolish

these blocks and torebuild on a humanscale, or even toprovide play-groups.The drug industry, thegovernment, thepharmacist, the tax-payer, and the doctorallhavevestedinterestsin “medicalizing”socially determinedstressresponses.

—MALCOLMLADER,“BENZODIAZEPINES:OPIUMOFTHEMASSES”

(1978)

Just because I canexplainyourdepressionusing terms such as“serotonin reuptakeinhibition” doesn’tmeanyoudon’thaveaproblem with yourmother.

—CARLELLIOTT,TheLastPhysician:WalkerPercyandtheMoralLifeofMedicine(1999)

Before Donald Klein’simipramine experiments,interpreting thecontentofone’s anxiety mattered alot:Whatdoesyourphobiaofheightsorratsor trainsmean?What is it trying to

communicate to you?Imipramine drainedanxiety of much of itsphilosophical meaning.Developments inpharmacology wereshowing anxiety to bemerely a biologicalsymptom, a physiologicalphenomenon, amechanical process whosecontentdidn’tmatter.Yetforphilosopherslike

Kierkegaard and Sartre,anxiety resolutely doeshave meaning. For them,as well as forpsychotherapists whoresistreducingbrainstatesto biology, anxiety is notsomething to be avoidedor medicated but ratherthe truest route to self-discovery, the road to (inthe sixties-inflectedversion of this idea) self-

actualization. Dr. W.believesthis.“Go into the heart of

danger,” he likes to say,quotingaChineseproverb,“for there you will findsafety.”For evolutionary

biologists, anxiety is amental and physiologicalstate that evolved to keepus safe and alive. Anxietyenhances our vigilance,

preparesustofightorflee.Being anxious canhelpfully attune us tophysical threats from theworld. Freud believedanxietyattunesusnot justto threats from the worldbut to threats fromwithinourselves. Anxiety, in thisview, is a sign that ourpsyche is trying to tell ussomething. Medicatingaway that anxiety instead

of listening to what it’strying to tell us—listeningto Prozac, as it were,instead of listening to ouranxiety—might not bewhat’s called for if wewant to become our bestselves. Anxiety can be asignal that somethingneeds to change—that weneed to change our lives.Medication risks blockingthatsignal.e

In Listening to Prozac,Peter Kramer engages thework of the novelistWalker Percy, whosewritinggrappleswithhowto cope with emotionalpain and spiritual longingin the age of biologicalpsychiatry.Whatgets lost,Percy’s stories and essaysask, when anxiety andanomie are medicatedaway?

Percy was well situatedto tackle these issues. The“hereditary taint” (asFreud called it) ofmelancholy ran thickthrough the bloodlines ofhis Southern family. Hisgrandfather, his father,and possibly his mother(who drove herself off abridge)committedsuicide;two of his uncles hadnervous breakdowns.

Percy’s father, LeRoy, alawyer, medicated hisdepression with alcoholandsoughttreatmentfromspecialists, traveling toBaltimoretomeetwiththeleading psychiatrists atJohns Hopkins in 1925.But modernpsychopharmacology wasnot yet available, and in1929 LeRoy succeeded inhis second attempt at

killing himself, shootinghimselfintheheadwitha20-gaugeshotgun.Walker’sresponsewasto

study science. Believingthat science wouldeventually explaineverything in the cosmos,includingthenatureofthemelancholy that killed somany members of hisfamily, he decided tobecome a doctor. His

medical training hardenedhis scientific materialism.“Ifmancanbe reduced tothe sum of his chemicaland biological properties,”as one of his biographerscharacterized Percy’sreasoningasayoungman,“why worry about ideals,orlackthereof?”But in 1942, Percy

contracted tuberculosisand had to drop out of

medical school, repairingtoasanatoriuminSaranacLake, New York, torecover. Streptomycin and—note this—isoniazid andiproniazidwere still a fewyears away from beingavailable as tuberculosisremedies,sotheprescribedtreatment was rest. Whileat the sanatorium, he fellintoadepressionandreadintensively—lots of

Dostoyevsky and ThomasMann, as well asKierkegaard and ThomasAquinas. Feelingphysicallyandemotionallyunwell, he underwent aspiritualcrisisinwhichhedetermined that sciencecould not, after all, solvethe problem of humanunhappiness. Eventually,influenced especially bythe writings of

Kierkegaard,hedecidedtomake a leap of faith andbecome a Catholic.f Howdifferently might Percy’slife and philosophy haveturned out if he had beentreated with iproniazidinstead of with acurriculum of Europeannovels and existentialphilosophy?Iproniazid,wenow know, would shortlybecome the MAOI

antidepressant Marsilid—adrug that might quicklyhave both cured histuberculosis and dispelledhis melancholy. He mightwell have returned to hismedicaltrainingandneverbecome a novelist. Hisopinion of biologicalpsychiatry might havebecome considerablywarmer.gPercy never lost his

respect for the scientificmethod. But he came todistrust the reductionistworldview that claimedscience as thephilosophical basis ofethics and of all humanknowledge. In fact, hecame to believe that thehigh rates of depressionand suicide in modernsocietywere owed in partto the cultural triumph of

the scientific worldview,which reduced man to acollection of cells andenzymes, withoutsupplying an alternativerepositoryofmeaning.In 1957, Percy wrote a

two-part article forAmerica, theweeklyJesuitmagazine. By focusing onthe biological, he said,psychiatry becomes“unable toaccount for the

predicament of modernman.” Guilt, self-consciousness, sadness,shame, anxiety—thesewere important signalsfrom the world and fromoursouls.Medicatingthesesignals away as symptomsof organic disease risksalienating us further fromourselves. “Anxiety is,”Percy wrote, “under oneframe of reference a

symptom to be gotten ridof;undertheother,itmaybe a summons to anauthentic existence, to beheededatanycost.”hMany times in his

writing, Percy alludes toKierkegaard’s idea thatworsethandespairistobein despair and not realizeit—to have anxiety but tohavebuiltyourlifearoundnot experiencing it. “We

all know perfectly wellthatthemanwholivesouthislifeasaconsumer,”hewrites in “The ComingCrisis in Psychiatry,” “asexual partner, an ‘other-directed’ executive; whoavoids boredom andanxietybyconsumingtonsofnewsprint,milesoffilm,yearsofTVtime;thatsucha man has somehowbetrayed his destiny as a

humanbeing.”If anxiolytic medication

mutesouranxiety,deafensustoit—allowsustobeindespairwithoutknowingit—does that somehowdeaden our souls? Percywouldseemtobelievethatitdoes.

I believe all of this, as faras it goes. I endorse the

philosophical stances ofWalker Percy and SørenKierkegaard. And yet howmuch credibility do Ihave?Afterall,hereIam,in my thirtieth year oftaking psychiatricmedications, withcitalopramandalprazolamand possibly still some oflast night’s clonazepamflowing through mybloodstreamasIwritethis

—my serotonergic andGABAnergic systemsboosted, my glutamateinhibited—agreeing withPeter Breggin that drugsare toxic andwithWalkerPercy that they diminishthe soul. Am I not aterribly compromisedvessel for delivering thisargument?And yet so, one might

say, was Percy, who took

sleeping medications forhischronicinsomnia.(Andwith good reason: hisfather’s brutal insomniaplayed a large role indriving him to suicide.)Psychiatric medications—for some people, in somesituations, some of thetime—work. To deny theschizophrenic chemicalremission from hispsychoticdelusions,orthe

bipolar patientpharmacological relieffrom his self-endangeringmanias and crushingdepressions—or, yes, thepanic-ravaged andhousebound individualsome medical defenseagainst anxiety—would becruel. One can be, Ibelieve, skeptical aboutthe claims of thepharmaceutical industry,

concerned about thesociologicalimplicationsofa population that is soheavily medicated, andattuned to the existentialtrade-offs involved intaking psychiatricmedicationswithoutbeingideologically in oppositionto the judicious use ofthesedrugs.On the other hand, I

know I would do well to

heed Percy, as well asmodernBigPharmacriticslike Edward DrummondandPeterBreggin,becausethe irony of what I havehad to ingest in order towritethissectionondrugsis obvious. I elevated myCelexa dosage, becamedependent on Xanax andKlonopin, and consumedheroic quantities ofalcoholtokeepmyanxiety

atbay.Afterfortyyearsofnever smoking a singlecigarette (because aftergettingmygrandmothertoquitsmokinginhersixties,I’dpromised tonever takeup the habit myself), Ismoked my first one atforty-one. After havingbeen so afraid ofrecreational narcotics(perhapsaninstanceoftheevolutionary adaptiveness

ofmy innatecaution) thatI’d never for forty yearstakensomuchasapuffofmarijuana nor indulged inany other nonprescribeddrug, I resorted indesperation (after readingFreud’senthusiasticpapersabout it) to tryingcocaineand also amphetamines.ManynightsIwouldbeginthe evening fueled bycaffeine and nicotine,

which I needed to propelme out of torpor andhopelessness—only toovershoot into quaking,quivering anxiety.Thoughts racing, handsshaking, I would end theevening taking aKlonopinand then perhaps aXanaxanddrinkingascotch(andthenanother andanother)to settledown.This isnothealthy.

More constructively, Ihave tried to draw onKierkegaard and Percy forbackboneandsolace,andIhave also tried yoga andacupuncture andmeditation. I would verymuch like to unlock my“inner pharmacy”—thatrepository of healthy,natural hormones andneurotransmitters that canbe activated, the antidrug

NewAgehealerssay,withmeditation andbiofeedback and better“inner balance”—butdespitemybestefforts,I’mfumblingwiththekeys.

*Thebirthofachildrankshighonthe famous Holmes and RaheStress Scale, which attempts toquantify the effects of variouskinds of life stresses on mental

andphysicalhealth.

† Often, escaping the office wasn’tenoughtostemthetideofpanic,so I took to walking severalblocks to Old North Church,wherePaulRevere’s famousone-if-by-land-and-two-if-by-sealanterns had supposedly beenhungin1775.I’dsitinanausterewoodenpewinthebackandgazeat the oil painting of Jesus thathangs behind the altar. In thatpainting, Christ’s face looks

kindly,hiseyessympathetic.Iamnot a hard-core atheist, but noram I a believer—I’m a who-knows-what-explains-all-thisagnostic,askepticwhooutofmyusual abundance of cautionrefusestobrazenlydenythatGodexists for fear of losing Pascal’swager and discovering too latethat he does. Yet in thosedesperateweeksinthesummerof2003, I would sit in Old NorthChurch and pray forthrightly to

thatpaintingofJesus.I’daskittopleasegivemepeaceofmind,ora sign that God existed,somethingIcouldgrabholdoftosteadymyself against the assaultof my nerves. In my quest forsuccor, I started readingmywaythroughtheBibleandahistoryofearlyChristianity,tryingtoseeifI could somehowreasonmywayto faith and the psychic andexistential serenity I thought itmightprovide.

Icouldn’t.AndwhileIdidfindsomething about the unadornedPuritan simplicity of the churchto be calming, my visits theredidn’t really help, either,especiallyduringthenadirofmyEffexorexperience.I’dtrytocalmmy breathing—but then I’d getoverwhelmed by claustrophobiaandpanicandhavetorushoutofthe church. I’d often end upshaking on a park bench,probably looking to passing

tourists like a homeless personsufferingdeliriumtremens.

‡ A series of studies in the 1980sfound imipramine, the tricyclicantidepressant, to be moreeffective thanProzac for treatingpatientswithdepressionorpanicdisorder. Imipramine alsotrounced Paxil in two studies inthe early 1980s of patients withdepression. In 1989, Paxil failedto beat a placebo in more thanhalfitstrials.Yetfouryearslater,

PaxilwasapprovedbytheFDA—and by 2000 it was the best-selling antidepressant on themarket, outselling Prozac andZoloft.

§ Carlsson wanted to pursuechlorpheniramine clinical trialsfor patients with anxiety anddepression,butheneverdid.Hisown lab research, as well assubsequent naturalisticobservations, showed thatchlorpheniramine may, without

anymodifications,beaseffectiveas any existing SSRI—which isintriguing becausechlorpheniramine has been onthemarket,underthetradenameChlor-Trimeton, as an over-the-counter medicine for pollenallergies since 1950. In 2006,Einar Hellbom, a Swedishresearcher, published a studysuggesting that patientsdiagnosed with panic disorderwho took chlorpheniramine for

their hay fever experienced aremission of their panicsymptoms while on the drug;whenthepatientswentoffChlor-Trimeton, even if they switchedtoanotherantihistamine,manyofthem found their panic attacksreturning.Hellbomsuggestedthatperhaps this means an effectivenonprescription SSRIantidepressant is sitting on theallergyremedyshelfofyourlocalpharmacy today—even though

scarcely any doctors, andcertainly no consumers, areaware of its potential in thisregard. “If chlorpheniramine hadbeen tested on depression in thenineteen seventies,” Hellbomwrites,“itisprobablethatasafe,inexpensiveSSRIdrugcouldhavebeen used some 15 years earlierthan [Prozac].… Chlorpheniraminemight havebeen the first safe, non-cardiotoxic and well-tolerated

antidepressant.Billionsofdollarsin the development andmarketingcostswouldhavebeensaved, and the suffering ofmillionsofpatientsalleviated.”

ThisisstrikingtomebecauseItook Chlor-Trimeton regularlyeach spring throughout mychildhood. I had alwaysattributed the lifting of mydepression and anxiety in AprilandMaytothelengtheningofthedaylightandtheapproachingend

oftheschoolyear.ButHellbom’spaper leadsme towonder ifmybrighteningmoodanddecreasingtensioneachspringwerearesultof my exposure to Chlor-Trimeton,theaccidentalSSRI.

‖ The tricyclics and MAOIs, incontrast, were “dirty,” or“nonselective,” in that theyaffected not just serotonin butalso norepinephrine, dopamine,and other neurotransmitters, afact thatwas thought to account

fortheirwiderangeofunpleasantsideeffects.

a Ironically, the early commercialsuccessofSSRIsowedalottothepublic furor over Valiumaddiction in the early 1970s,which had drivenbenzodiazepines out of favor.When the FDA approved SSRIsfor the treatment of depression,that caused the number ofdepression diagnoses toskyrocket, even as rates of

anxiety diagnosis fell. But whenthe FDA subsequently approvedSSRIs for the treatment ofanxiety, the number of anxietydiagnosesroseagain.

b These findings are controversialand continue to be debatedfiercely on psychiatry andpsychologyblogs.

c Much more so than in, say,France, where tranquilizerconsumptionratesarehigher,butperhaps even less so than in

Japan, where SSRI consumptionratesaremuchlower.

d Another colleague of Dr. W.’s—let’s call him Dr. G.—was aneminent psychoanalyticallytrained psychiatrist who, late inhis career, fell into a severeclinical depression. Dr. G.checked himself into ChestnutLodge, a psychoanalyticallyoriented psychiatric hospital inRockville, Maryland. For years,Dr. G. had been a professional

opponentofbiologicalpsychiatry,arguing that Freudian talktherapywasthebestwaytotreatanxietyanddepression.Butdailysessions of analyticpsychotherapyprovidedDr.G.norelief from his suffering. Onlywhen he consented to go onantidepressants did his conditionimprove.Dr.G.’sdepressionlifted—but he now found himselfconfronted with a professionalcrisis: Was psychoanalytic

psychotherapy,thefoundationonwhich he’d built his career, achimera? He died not longthereafter.

eEdwardDrummond,apsychiatristinNewEngland,usedtoregularlyprescribe benzodiazepinetranquilizers to his patients inorder to reduce their anxiety.Today, he strongly believestranquilizers are a significantcause of chronic anxiety. TakingXanax orAtivan can temporarily

alleviate acute anxiety,Drummond says, but at the costof allowing us to avoid dealingwithwhatever issues are causingthatanxiety.

f Percy’s conversion prompted hisbestfriend,thenovelistandCivilWar historian Shelby Foote, totellhim,“Yours isamind in fullintellectualretreat.”

gPeterKramermakesobservationsalong these lines in Listening toProzac.

h Themes of anxiety, nervousdisorders, and existential dreadrun through much of Percy’swriting. In The Second Coming,Will Barrett, a retired lawyer,must cope with a strangeaffliction that descends on himafter the death of his wife, afeeling of depressionaccompaniedbyadisturbanceofhis internalgyroscope,ahitch inhis golf swing, and what hisdoctorsbelievemaybepetitmal

seizures. Will suspects hisneuroticailmentiscausedbytheworld’s being “farcical.” But onedoctor suspects “a smallhemorrhage or arterial spasmnearthebrain’slimbicsystem.”IsWill’s unhappiness a problem ofmeaning?Oraquirkofbiology?

As the novel progresses,Will’smalaise deepens; his faintingspellsbecomemorefrequent,andhe becomes filled with religiousyearning. Eventually, his family

commits him to the hospital,where a doctor diagnoses himwith Hausmann’s syndrome, adisease (invented by Percy)whose symptoms include, inaddition to seizures, “depression,fugues, certain delusions, sexualdysfunction alternating betweenimpotence and satyriasis,hypertension, and what [Dr.Hausmann] called wahnsinnigeSehnsucht”—“inappropriatelonging.” The disease is caused,

Will’s doctors explain, by asimple pH imbalance and istreatedbythesimplestofdrugs—a hydrogen ion, a single nucleusof one proton. Will is consignedtoanursinghome,wherehispHlevels can be checked every fewhours. “Remarkable, don’t youthink,” says his doctor, “that afew protons, plus or minus, cancause such complicated moods?Lithium, the simplest metal,controls depression. Hydrogen,

the simplest atom, controlswahnsinnige Sehnsucht.” Will,ostensibly cured and living hiscircumscribed nursing-homeexistence, marvels: “How odd tobe rescued, salvaged, convertedbythehydrogenion!Aprotonassimpleasabilliardball!Diditallcomedowntochemistryafterall?Hadhe…poundedthesandwithhis fist in a rage oflonging … because his pH was7.6?”

Percy, writing here in the late1970s, when the “catecholaminehypothesis of affectivedisorders”and “norepinephrine theory ofdepression” were taking hold, ismocking the pretensions ofbiological reductionism. Byreducing Will’s humanity—notonly his depression but his ideasand his longings—to hishydrogen molecules, Percy isessaying a critique of modernpsychopharmacology, which in

hisviewpathologizesalienation.

Sevenyearslater,ontheeveofProzac’s American launch, Percypublished an even bluntercritiqueofbiologicalmaterialism.TheThanatosSyndromefeaturedacharacternamedThomasMore,apsychiatristwhohadappearedinanearliernovel,LoveintheRuins.In The Thanatos Syndrome, Dr.More, who has recently beenreleased from jail,where he hadbeen serving time for illegally

selling the benzodiazepineDalmaneattruckstops,returnstohis hometown of Feliciana,Louisiana,tofindeveryoneactingstrangely.Thewomenofhistownhave developed a propensity forpresenting themselves rearwardforsex.Hisownwife,inadditionto exhibiting this predilection,has developed a computerlikeaptitude for playing bridge thathas propelled her to success innational tournaments. He notes

that anxious women havesuddenly lost weight and self-consciousness while gainingboldness, sexual voracity, andemotional insensitivity. Theyshed “old terrors, worries,rages…likelastyear’ssnakeskin,and in its place is a mild fondvacancy, a species of unfocusedanimalgoodspirits.” It turnsoutthat some supercilious civicleaders—includingthedirectorofthe Quality of Life Division, a

federal agency that overseeseuthanasiaprograms—havetakenituponthemselvestointroduceachemical called heavy sodiuminto the water supply, likefluoride,inaneffortto“improve”thesocialwelfare.Heavysodiummakes people more placid, lessself-conscious,andmorecontent.This is not necessarily a goodthing: in losing theiranxietyandself-consciousness, the citizensofFeliciana are becoming less

human. Dosed with heavysodium,Feliciana’swomenarenolonger “hurting, they are notworrying the sameoldbone,butthere is something missing, notmerely the old terrors, but asense in each of her—her what?her self?” Dr. More is skeptical,but the heavy sodium advocatestry to arguehimaround to theirway of thinking. “Tom, we cansee it!” one zealous championtells him. “In a PETscanner! We

canseetheglucosemetabolismofthelimbicsystemraisingallkindsofhellandgettingturnedofflikea switch by the cortex. We cansee the locus ceruleus and thehypothalamus kicking in, libidoincreasing—healthy heterosexuallibido—and depressiondecreasing—we can see it!”Mocking the arrogance ofbiological psychiatry, Percymeans to warn that to medicateaway guilt, anxiety, self-

consciousness, andmelancholy istomedicateawaythesoul.

PARTIV

NurtureVersusNature

CHAPTER8

SeparationAnxiety

The great source ofterror in infancy issolitude.WILLIAMJAMES,The

PrinciplesofPsychology(1890)

When did my anxietybegin?Was it when I, as atoddler, would throw epictantrums, screamingrelentlessly and bangingmyheadonthefloor?The questions that

confronted my parentswere these: Was mybehaviormerely a slightlyextreme but nonethelesstypical manifestation oftheterribletwos—ordiditlieoutsidethebandofthenormal? What is thedifference betweenchildhood separationanxiety as a normaldevelopmental stage andseparation anxiety as a

clinical, or preclinical,condition? Where is theline betweentemperamental inhibitionas a normal personalitytrait and inhibition as asymptom of pathology—asign of, say, incipientsocialanxietydisorder?On the matter of mytantrums,mymother’sDr.Benjamin Spock manualwasnotdispositive,soshe

tookmetothepediatricianand described mybehavior. “Normal,” washis conclusion, and hisadvice,inkeepingwiththelaissez-faire approach tochild rearing of the early1970s,was to letme “cryit out.” So my parentswouldwatchindistressasI lay on the floor,screaming and writhingand smashingmyheadon

the ground, sometimes forhoursatatime.Then what to make of

myextremeshynessatagethree? When my mothertookmetomyfirstdayofnursery school, shecouldn’t (or wouldn’t—separation anxiety cutsboth ways with childrenandparents)leavebecauseI clung to her leg andwhimpered. Still,

separation anxiety in athree-year-old is wellwithin the spectrum ofnormal developmentalbehavior, and eventually Iwas able to stay at schoolforthreemorningsaweekby myself. And while Iclearly exhibited signs ofan “inhibitedtemperament”—shy,introverted, withdrawingfrom unfamiliar situations

(and in a lab I probablywould have displayed ahair-trigger startle reflexand high levels of cortisolinmyblood)—noneofthiswas necessarily evidenceof emergingpsychopathology.Today, it’s not hard to

see that my earlybehavioral inhibition wasa harbinger of my adultneurosis—but that’s only

in retrospect, seeing myanxiety as an unfoldingnarrative.Atagesix,whenIwasin

first grade, two newproblems set in. The firstwas an intensifiedresurgence of myseparation anxiety (aboutwhichmoreinamoment).The second was the onsetof emetophobia, or thefear of vomiting, my

original, most acute, andmost persistent specificphobia.The first presenting

symptom for some 85percent of adults withanxiety disorders,accordingtodatacollectedbyHarvardMedicalSchoolresearchers, is a specificphobia developed as achild. The same data,basedoninterviewswitha

quarterofamillionpeoplearoundtheworld,hasalsorevealed that earlyexperiences with anxietytend to compound andmetastasize. A child whodevelops a specific phobia—say, a fear of dogs—atagesixisnearlyfivetimesmore likely than a childwithout a fear of dogs todevelop social phobia inher teenage years; that

same child is then 2.2times more likely than achildwithoutanearlydogphobia to develop majordepressionasanadult.“Fear disorders,” says

Ron Kessler, the head oftheHarvardstudy,“haveavery strong pattern ofcomorbidity over time,with the onset of the firstdisorder stronglypredicting the onset of a

second, which stronglypredicts the onset of athird, and so on.”(“Comorbidity” is themedical term for thesimultaneous presence oftwo chronic diseases orconditions in a patient;anxietyanddepressionareoften comorbid, with thepresenceofonepredictingthepresenceoftheother.)“Fearofdogsatagefiveor

ten is important notbecause fear of dogsimpairsthequalityofyourlife,”Kesslersays.“Fearofdogs is important becauseit makes you four timesmorelikelytoendupa25-year-old, depressed, high-school dropout singlemother who is drugdependent.”*While the nature of the

link between childhood

phobia and adultpsychopathology is notclear, the fact of it is—which is why Kesslerinsists that earlydiagnosisand treatment is soimportant. “If it turns outthat dog phobia doessomehow cause adultpsychopathology, then thesuccessful early treatmentof phobic children couldreduce later incidence of

depression by 30 to 50percent. Even if it’s onlyby 15 percent, that’ssignificant.”The numbers from

Kessler’sstudywouldseemto lend a statisticalfatedness to theprogressionofmyanxiety:fromspecificphobiaatagesix to social phobiastartingaroundageelevento panic disorder in my

late teens to agoraphobiaand depression in youngadulthood. Ihavebeen, inmy pathogenesis—thedevelopment of mypathology—a textbookcase.

Missingsomeonewhoislovedand longedfor isthe key to anunderstanding ofanxiety.

—SIGMUNDFREUD,Inhibitions,Symptoms,andAnxiety(1926)

When I was six yearsold, my mother startedattending law school atnight. My father says thiswas at his instigation,becausehe’dseenhowmymother’s mother hadbecome depressed andalcoholicasastay-at-home

suburban housewifewithout professionalaspirations. My mother,for her part, says that itwas over my father’sobjections that she startedstudying law. She adds,furthermore, that hermother was neitherdepressednoranalcoholic.(Mymother is presumablythe better authority here,butforwhatit’sworth,my

grandmother, whom Iloved dearly, often didsmellappealinglyofgin.)The powerfulrecrudescence of myseparation anxietycoincided with thebeginning of my mother’sfirst year in law school.Each day during firstgrade, I would be drivenhomefromschool inacarpool to be greeted by one

ofaseriesofneighborhoodbabysitters. Thebabysitters were all verynice. Nevertheless, nearlyevery evening ended thesameway:withmepacingaround my bedroomwaitingdesperatelyformyfather tocomehomefromwork. Because nearlyeverynight for about fouryears—and thenintermittently for about

tenmoreyearsafterthat—I was convinced that myparents were not cominghome, that they had diedorabandonedme,andthatI had been orphaned, aprospect that wasunbearably terrifying tome.Eventhougheverynight

providedyetanotherpieceof evidence that myparents always did come

home,thatneverprovidedreassurance. This time, Iwas always convinced,they’re really not comingback. So I would pacearound my room, and siton the radiator peeringhopefullyout thewindow,and listen desperately forthe rumble of my father’sVolkswagen. He wassupposed to be home byno later than 6:30, so as

theclockclickedpast6:10and 6:15, I would beginsuffering my nightlyparoxysms of anxiety anddespair.Sitting on the radiator,nose pressed up againstthewindow,I’dtrytowillhim home, mentallypicturing his return—theVolkswagen turning offCommon Street and ontoClark Street, heading up

the hill and left ontoClover,thenrightontoourstreet,Blake—andthenI’dlook down the street andlistenfortherumbleofthecar. And … nothing. I’dstareatmybedroomclock,my agitation increasing asthe seconds ticked by.Imagine you have justbeentoldthatalovedonehas died in a car crash.Every night produced the

same fifteen to thirtyminutes of effectivelybelieving I had been toldjust that—a half hour ofexquisite agony duringwhich I was absolutely,resolutely convinced thatmy parents had died orthat they had abandonedme—evenasthebabysitterblandly played boardgames with my sisterdownstairs. And then

finally, usually by six-thirty and almost alwaysby seven, the Volkswagenwould come motoringdown the street and turninto the driveway, and aburst of relief-borneeuphoria would cascadethrough me: He’s home,he’s alive, I haven’t beenabandoned!And then thenextnightIwouldgothroughthisall

overagain.Weekends when myparents went out togetherwereevenworse.Myfearsof abandonment were notrational.MostofthetimeIwas convincedmyparentshad died in a car crash.Other times I was suretheyhadsimplydecidedtoleave—eitherbecausetheydidn’tlovemeanymoreorbecause they weren’t

reallymyparentsafterall.(SometimesI thoughttheywere aliens; sometimes Ithought they were robots;at times I was convincedthatmysisterwasanadultmidget who had beentrained toplay thepartofa five-year-old girl whileher colleagues, myparents, performedwhateverexperimentstheywere carrying out before

abandoningme.)My mother, more

attunedtomyanxietythanmy father was, clued intohow I would start myworrying well in advanceof when they hadpromised to be home. Sowhen they were leavingand I would ask, ritually,“What’sthelatestyou’llbeback?” my mother wouldannounceatimefifteenor

twenty minutes later thanwhen she actuallyestimated they wouldreturn. But I cottoned onto this gambit soonenough, so I would factorin that extra time andbegin my worried pacingforty-five minutes or anhour before the statedlatest time. And mymother,pickinguponthis,moved her stated return

timestilllater,butIwouldpick up on that—and wewereoffandrunningonakindofarmsraceofstatedand assumed return timesthat eventually renderedanything she saidmeaningless tome, somyanxiety would rise fromthemomenttheyleft.This weekend worryingwenton, Ihate tosay, fora long time. As a young

teenager, I sometimescalled (or forcedmysistertocall)partiesmyparentswereat tomakesure theywerestillalive.OnseveraloccasionsIwokeneighbors(and once the minister ofthe Episcopal churcharound the block) bybangingontheirdoorslateintheeveningtotellthemthat my parents weren’thome and that I thought

theymightbedeadandtoplease call the police.When I was six, this wasembarrassing to myparents; when I wasthirteen,itwasmortifying.By the time I was

twelve, even being alonein my room at night—down the hall from myparents, less than fifteenfeetaway—hadbecomeanordeal. “Do you promise

everythingwillbeokay?”Iwould ask my motherwhen she tuckedme in atnight.Asmyemetophobiagot worse, I worried Iwould wake up vomiting.Thismademeanxiousandqueasyatbedtime.Feelingthatway one night, I toldmy mother, “I’m notfeeling well. Can youpleasebeespeciallyonthealert tonight?” She said

she would be. But then afew nights later, I musthave been feeling evenmore nervous than usual,because I said, “Can youplease be especially,especially,especiallyonthealerttonight?”IremembertheexactwordingbecauseI began asking thatquestion every night.Eventually, this escalatedinto a ritual, one with a

precise and weirdsequence to it, thatpersisted until I went tocollege.“Do you promiseeverythingwillbeokay?”“Ipromise.”“And will you beespecially, especially,especially, especially,especially three hundredfifty-seven and a quartertimesonthealert?”

“Yes.”Like a psalm, with thestress always on the fifth“especially,” every nightforyears.My separation anxietyaffected nearly everyaspect of my life. I was areasonably coordinatedathleteasapreadolescent,but here’s how my firstbaseball practice ended:withme,agesix,cryingin

the dugout, alongside akindly but puzzled coach.(Ineverwentback.)Here’s how my firstbeginners’ swimminglessonended:withme,ageseven, fearfully, tearfullyrefusing toget in thepoolwiththeotherchildren.Here’s how my firstsoccer practice ended:withme,ageeight,cryingon the sideline with the

babysitter who’d broughtme, resisting entreaties tojoin the other boys doingdrills.Here’s how I spent myfirstmorningatdaycamp,when I was five: sobbingbymycubby,cryingthatImissed my mommy andwantedtogohome.Here’s how I spent thefirst two hours atmy first(and only) overnight at

camp, when I was seven:sobbinginthecornerwitha passel of befuddledcounselors trying, seriallyand without success, toconsoleme.Here’s how I spent thedrive to college with myparents: sobbing in thebackseat, consumed byanxiety and anticipatoryhomesickness, worriedthatmyparentswouldnot

lovemeafterIwentawaytocollege—“away,”inthiscase, being a mere threemiles from my parents’house.Why could I never feelassuredofmyparents’loveor protection? Why wereordinary childhoodactivities so difficult?What existentialreassurance was I seekingin my nightly call-and-

responsewithmymother?

The first anxiety is thelossoftheobjectintheform ofmaternal care;after infancy andthroughout the rest oflife loss oflove…becomesanewand far more abidingdanger and occasionforanxiety.

—SIGMUNDFREUD,TheProblemofAnxiety

(1926)

In1905,SigmundFreudwrote,“Anxietyinchildrenis nothing other than anexpression of the fact thattheyarefeelingthelossofthepersontheylove,”andso-called separationanxiety has remained afocus of researchers and

clinicians ever since.Decades of studies bypsychologists,primatologists,anthropologists,endocrinologists,ethologists, and othershave revealed again andagain,inmyriadways,theparamount significance ofthe early mother-childbond in determining thelifelong well-being of the

child. The nature of thatmother-child relationshipstarts getting establishedat the moment the infantenters the world—with“the trauma of birth,” asthe early Freudianpsychoanalyst Otto Rankput it—if not earlier thanthat. Experiences in thewomb and during infancycan have profound effectson a child’s sense ofwell-

beingthat last fordecades—and that can even,according to recentresearch, persist intosubsequent generations ofoffspring.Yetforallhisastutenessabout the role of earlychildhood experiences inpredicting lifelongemotional health, Freudwas formostofhis careerstrangelyblindtotheways

early parent-childrelationships affect thehumanpsyche.This seemsto have been especiallytrueinthecaseofhisownpsyche.For many years, Freudendured a debilitatingphobiaoftraintravel.Thetrainphobiafirstpresenteditself,according toFreud’sown account, in 1859,when he was three years

old. His father’s woolbusiness had collapsed,prompting the Freuds torelocate from Freiberg, asmall Austro-Hungariantown (now P?íbor, in theCzech Republic), toVienna. When the familyarrivedatthetrainstationin Freiberg, youngSigmund was filled withdread: the gas-jet lightsthat illuminated the

stationmade him think of“soulsburning inhell”;hewasterrifiedthatthetrainwoulddepartwithouthim,taking his parents andleaving him behind. Foryears thereafter, traintravel caused him anxietyattacks.His life wascircumscribedbyhistravelphobia.Foralongtime,heprofessed a desire to visit

Rome—but was deterredfrom going by what hecame to call his “Romeneurosis.”Whencompelledto travel anywhere bytrain with his family, hewouldbookhimself intoaseparate compartmentfromhiswifeandchildrenbecause he was ashamedto have them witness hisfits of anxiety. Hecompulsively insisted on

getting to railway stationshours in advance ofdeparture because heforever retained theintense fear of being leftbehind that he firstexperienced as a three-year-old.A modern therapistmight naturally attributeFreud’s travel phobia tohis childhood fears ofabandonment. Freud

himselfdidnot.Rather,ashe wrote to his friendWilhelmFliessin1897,hebelieved that whatprompted his anxiety wasseeinghismothernakedintheir train compartmentwhile en route fromFreiberg to Vienna.Witnessing this at a timewhen his “libido towardmatrem had awakened”must have aroused him

sexually, Freud surmised,and even as a three-year-old hewould have knownthe taboo nature of suchincestuous desire andwould therefore haverepressed it. This act ofrepression, he theorized,generated anxiety that heneurotically transmutedinto a phobia of trains.“You yourself have seenmy travel anxiety at its

height,”heremindsFliess.Tellingly,Freudcouldn’tactually recall seeing hismother nude on the train;he just supposed that hemust have and that he’dthen pushed the imagedownintohisunconscious.From this (strained)suppositionhegeneralizedthat all train phobiaderives from repressedsexual desire and that

those who are “subject toattacks of anxiety on thejourney” are actuallyprotecting themselves“againstarepetitionofthepainful experience by adreadofrailway-travel.”On the basis of this(quite likely imagined)experience,Freudovertheyears elaborated hisOedipus complex andconcludedthatthiswas“a

universal event in earlychildhood.” He wouldeventually make theOedipus complex thecenterpiece of hispsychoanalytic theory ofneurosis.†Wasmy own separation

anxiety as a young boy—and are my abidinganxiety and dependencyissues as an adult—attributable to my

repressed sexual feelingsformymother?Itcertainlynever felt thatway tome.Of course, Freud wouldsay that it wouldn’t havefelt that way: his wholepoint was that suchfeelings are repressed intothe unconscious andtransmuted into anxietyabout other things—trainsor heights or snakes orwhatever. And in support

ofFreud,Iconfessthereisthis:Thenameofmy firstcrush, in fifth grade, wasAnne;thenameofmyfirstpostcollege girlfriend,whom I dated for threeyears, was Ann; the girl Idated immediately afterAnn, fornearly twoyears,wasnamedAnna;thegirlIleft Anna for was namedAnne;andmywife’snameis Susanna. My mother’s

name? Anne, of course. Iusedtojokethatdatingallthose Anns, Annes, andAnnas reduced thelikelihoodIwouldcallanyof them by the wrongname—because even thewrong name would soundlike the right one. ButFreudwouldsaythatwhatI was really in danger ofcalling them—that what Iwasseekingwithall those

Anns,Annes, andAnnas—was Mom. Lending stillfurther Oedipaldeterminism to myromantic relations is thefact that my paternalgrandmother was alsonamed Anne—meaningthat my father alsomarriedawomanwiththesamenameashismother.Butthereis,ofcourse,aless sexual explanation for

how Freud’s earlychildhood experiencesmight have produced hislifelong anxiety and trainphobia.ThefirstyearsofFreud’s

life were colored by loss,and by the waveringattention of his mother,Amalia. Shortly after hewas born, in 1856, hismother got pregnantagain, giving birth to

another son, Julius. Lessthan a year later, Juliusdied, felled by anintestinal infection. At thetime, the Freud familylived in a one-roomapartment, so it’s likelythatSigmund,asatoddler,witnessedatclosehandhisbrother’s death and hisparents’ reaction to it.Some of Freud’sbiographers have

suggested that Julius’sdeath sent Amalia into adepression that wouldhavemadeherremoteandunavailable to Sigmund.(Depression in mothers ofchildren this age can behighly predictive ofanxiety and depression inthose children later inlife.) With his motheremotionally unavailable,Freud naturally turned to

an alternative maternalfigure—the nursemaid, aCzech Catholic woman,who cared for him in theearly years of his life. Butwhile Sigmund was still asmallchild,thenursemaidwas caught stealing andsent to jail; he never sawheragain.The logical conclusion

herewouldseemtobethatFreud’strainphobiawasa

response to the fear ofabandonmentproducedbythis string of childhoodlosses—the death of hisbrother, the emotionalunavailability of hismother, and the suddendisappearance of hisprimary caretaker. ButFreudremained fixatedonproving the rightness ofhis sexual explanations ofanxiety and his Oedipus

complex. He would exilefrom the fold anyone(including Alfred Adler,CarlJung,andOttoRank)who dared question theircentrality.

Allanxietygoesbacktotheanxietyatbirth.—OTTORANK,TheTraumaofBirth(1924)

Later in his career, asFreud moved from hisrepressed libido theory ofanxiety tohis intrapsychicconflict theory, he beganto take more account ofthe way in which parent-child relations—“objectrelations,” in thepsychoanalytic argot—relatedtoanxiety.The final shifts in

Freud’s theory of anxiety

were motivated by hisdisavowal of a bookwrittenbyoneofhismostdevoted acolytes. OttoRank, the secretary ofFreud’s ViennaPsychoanalytical Society,had intended The TraumaofBirth,publishedin1924,asa tribute tohismentor.(The book is dedicated toFreud,“theexploreroftheunconscious, creator of

psychoanalysis.”) Rank’sbasicargument,elaboratedat great length, was thatbirth—both the physicalact of passing through theuterine canal and thepsychological fact ofseparation from themother—is so traumaticthat the experiencebecomes the template forall future experiences ofanxiety. In making this

claim, Rank was buildingonwhatFreudhimselfhadalreadyargued.“Theactofbirthisthefirstexperienceof anxiety, and thus thesource and prototype ofthe affect of anxiety,”Freud had written in afootnote to the secondeditionofTheInterpretationofDreams in1908,andherepeated this notion in aspeech he gave to the

Vienna PsychoanalyticalSociety the followingyear.‡ButThe Trauma of Birth

was a work of suchextravagant interpretivebriothatFreud,thoughnostranger to extravagantinterpretive leaps himself,found it alienating andbewildering, and hedevoted a full chapter ofThe Problem of Anxiety to

renouncing it.§ Rank’sarguments forcedFreud towrestle once more withthe ways in which earlylife experiences arerelevant to anxiety. Thisled him to revise his owntheoryofit.In the final chapter of

The Problem of Anxiety,Freudgivesbriefattentionto what he called the“biological factor,” by

which he meant “theprotracted helplessnessand dependence of theyoung of the humanspecies.”Freud writes that “the

human infant is sent intotheworldmoreunfinishedthan the young [of otherspecies]”—meaning thathumans emerge muchmorehighlydependentontheir mothers for their

survival than do otheranimals.‖Theinfantseemsto be born with aninstinctive sense that themother can providesustenanceandsuccor,andlearns very quickly thatwhereas the mother’spresenceequalssafetyandcomfort, her absenceequals danger anddiscomfort.Observingthis,Freud concluded that the

earliest human anxiety,and thus to some degreethe source of allsubsequent ones, is areactionto“thelossoftheobject”—the “object”being the mother. “Thisbiological factor ofhelplessness thus bringsinto being the need to beloved which the humanbeing is destined never torenounce,” Freud writes.

The first anxiety is aboutthelossofamother’scare;throughout the balance oflife, “loss oflove … becomes a newand far more abidingdanger and occasion foranxiety.”InthefinalpagesofThe

Problem of Anxiety, Freudbriefly develops the ideathat phobic anxiety inadults is the residue of

human evolutionaryadaptations: phobias ofsuch things asthunderstorms, animals,strangers,beingalone,andbeinginthedarkrepresent“theatrophiedremnantsofinnate preparedness”against real dangers thatexisted in the state ofnature.Forearlymanandwoman,beingalone,or inthe dark, or bitten by a

snake or a lion—and, ofcourse, the separation ofan infant from hismother—were legitimate mortalthreats. In all of this,Freudwasanticipatingtheworkof thebiologists andneuroscientistswhowouldstudy phobias in thedecadesahead.aIn other words, Freud

was,inhisseventies,inanaddendum to one of his

finalworks,finallymovingcloser to what wouldbecome the modernscientific understanding ofanxiety.Butbythenitwastoo late. Freud’s followerswere off to the raceswith“Oedipus conflicts” and“penis envy” and“castration anxiety”—and“inferiority complexes”(Adler)andthe“collectiveunconscious” (Jung) and

“death instincts” (MelanieKlein) and “oral and analfixations” (Karl Abraham)and so-called “phantasies”about“thegoodbreastandthe bad breast” (Kleinagain). For a generation,as the field grew in theyears leading up to andfollowing the SecondWorldWar, the prevailingpsychoanalytic view wasthatanxietywascausedby

dammed-upsexualdrives.

While parents are heldtoplayamajorrole incausing a child todevelop a heightenedsusceptibility to fear,their behaviour is seennot in terms of moralcondemnation but ashavingbeendeterminedbytheexperiencestheythemselves had as

children.—JOHNBOWLBY,Separation:AnxietyandAnger(1973)

The person mostresponsible for unlockingthemysteriesofseparationanxiety, and for installingthe concept near thecenter of modernpsychiatry,wastheBritish

psychoanalyst JohnBowlby,who did asmuchas anyone to rescuepsychoanalysis from itsmore torturous theoreticaloverreaching. Trained inthe 1930s by Freud’sprotégé Melanie Klein,Bowlby would go on todevelop what has becomeknown as attachmenttheory—the idea that anindividual’s anxiety level

derives largely from thenature of the relationshipwith early attachmentfigures, most commonlythemother.Bowlby was born in

1907 to an aristocraticsurgeonwhoministeredtothe king of England, andhe would later claim thathis “was a very stablebackground.” But it’s nothard to see that Bowlby’s

clinical and researchinterests, like Freud’s,were informedbyhisownchildhood experiences.Bowlby’s mother,according to thepsychologistRobertKaren,was “a sharp, hard, self-centered woman whonever praised the childrenand seemed oblivious totheir emotional lives”;Bowlby’s father, generally

absent,was “something ofan inflated bully.” TheBowlby children atecompletely apart fromtheir parents until theywere twelve years old—atwhich age they would bepermitted to join theirparents only for dessert.BythetimeBowlbyturnedtwelve, he’d already beenaway from home, atboarding school, for four

years. Publicly, he wouldalwayssayhisparentshadsent him away becausetheywantedtoprotecthimfrom the bombs theyfeared German zeppelinswould drop on Londonduring the First WorldWar; in private, however,he confessed that he’dhatedboardingschoolandthat he wouldn’t send adogawaysoyoung.b

Psychoanalysts beforeBowlby were generallyuninterestedintheday-to-day relationship betweenparentsandchildren.Whatinterest theydidhavewasfocused on breast-feeding,toilet training, and(especially) instances inwhich a child witnessedhis parents having sexualintercourse. Anyone whoplacedundueemphasison

a child’s real experience—as opposed to on hisinternal fantasies—“wasregarded as pitifullynaive,” Bowlby wouldlater recall. Once, whilestill amedical student, hewatchedwith dismay as aseries of case studiespresented at the BritishPsychoanalytic Societytraced patients’ emotionaldisorders to childhood

fantasies.Unabletobearitany longer, he blurted:“But there is such a thingasabadmother!”Thissortof thing did not endearhim to the psychoanalyticestablishment.In 1938, while still in

good standing with themandarins ofpsychoanalysis, he wasassigned as a supervisor adoyenne of the Freudian

establishment, MelanieKlein.cBowlby would sooncome to find himself atoddswithmanyofKlein’sviews—suchasthatbabieswere seething miasmas ofhatred, libido, envy,sadism, death instincts,and rage against therestraining superego andthat neuroses arosebecause of conflicts

betweenthe“goodbreast”andthe“evilbreast.”Kleinherself was by mostaccounts an unpleasantperson; Bowlby wouldlater describe her as “afrightfullyvainoldwomanwhomanipulated people.”But what most appalledhim was Klein’s disregardfor the actual relationshipbetweenmotherandchild.The first case he treated

under Klein’s supervisionwas an anxious,hyperactive young boy.Bowlbynoticedrightawaythat the boy’smotherwas“an extremely anxious,distressed woman, whowaswringingherhands,ina very tense, unhappystate.” To him it seemedobvious that the mother’semotional problems werecontributing to the boy’s

and that a sensible courseoftreatmentwouldincludecounseling for themother.But Klein forbade Bowlbyto talk to the woman.When the mother waseventually admitted to amental hospital after anervous breakdown,Klein’s response wasexasperation at having tofind a new patient, sincethere was no longer

anyone who could bringthe boy to hisappointments. “The factthat this poorwomanhadhad a breakdown was ofno clinical interest to[Klein]whatever,”Bowlbywould say later. “Thishorrified me, to be quitefrank.Andfromthatpointonwardsmymissioninlifewas to demonstrate thatreal-lifeexperienceshavea

very important effect ondevelopment.”In1950,thechiefofthemental health section ofthe World HealthOrganization, RonaldHargreaves, commissionedfrom Bowlby a report onthepsychologicalproblemsof the thousands ofEuropean childrenrendered homeless by thedisruptions of World War

II. Bowlby’s report,Maternal Care and MentalHealth,urgedgovernmentsto recognize that amother’s affection was asimportant for mentalhealth “as are vitaminsand proteins for physicalhealth.” Strange as itmayseem now, in 1950 therewasn’tmuchrecognitionoftheeffectsofparentingonpsychologicaldevelopment

—especially withinpsychiatry, wheretreatment still oftenfocused on the processingofinnerfantasies.dBowlby’s early research

focusedonwhathappenedwhen children, throughthe intrusions of war orillness, were separatedfrom their mothers.Psychoanalytic andbehaviorist theory held

that separations from themotherdidn’treallymatteraslongasthechild’sbasicneeds (food, shelter) weretaken care of. Bowlbyfound that not to be trueat all: when youngchildren were separatedfromtheirmothersforanysubstantial period of time,they tended to displayacute distress. Bowlbywondered if the effects of

prolonged separation inyoung childhood couldleadtomentalillnesslateron. The children whobecame clingy uponpostseparation reunions,Bowlby suspected, werethosewhowouldgrowupto be needy, neuroticadults; those who becamehostile were those whowould eschew intimacyand have difficulty

forming deeprelationships.Throughout the 1940s

and 1950s, while servingas head of the children’sdepartment at a healthclinicinLondon,hebeganto explore how the earlyday-to-day relationshipbetweenmother and child—what hewould come tocalltheattachmentstyle—affected the child’s

psychological well-being.He found the samepatterns again and again.Whenmothershad“secureattachment” relationshipswith their infants ortoddlers—the motherscalmandavailablebutnotsmothering oroverprotective—thechildren were calmer,more adventurous,happier; they struck a

healthy balance betweenmaintaining proximity totheir mothers andexploring theirenvironment.Securely attachedchildren were able tocreatewhatBowlbycalled“an internal workingmodel” of their mothers’love that they could carryout into the world withthem throughout their

lives—an internalizedfeeling of psychologicalsecurity, a sense of beinglovedandofbeing safe inthe world. But when themothers had “insecure” or“ambivalent” attachmentrelationships with theirtoddlers—if the motherswere anxious andoverprotective oremotionally cold andwithdrawn—the children

were more anxious andless adventurous; theywould cling to theirmothers and become veryagitatedinresponsetoanyseparation.Over the next four

decades, Bowlby and hiscolleagues would developa typology of attachmentstyles. Secure attachmentinchildhoodpredictedlowanxiety levels and a

healthydegreeofintimacyin adult relationships.Ambivalent attachment—which described thosechildren who clung mostanxiously, who displayedhighlevelsofphysiologicalarousalinnovelsituations,andwhoweremuchmoreconcernedwithmonitoringtheir mothers’whereabouts than inexploring the world—

predicted high levels ofanxiety in adulthood.eAvoidant attachment in achild—which describedthose kids who tended towithdraw from theirmothers after separations—predicted a dislike ofintimacyinadulthood.fThe person mostresponsible for helpingBowlby develop thistaxonomy of attachment

styleswasthepsychologistMary Ainsworth. In 1929,Ainsworthwasafreshmanat the University ofToronto plagued byfeelings of inadequacy.That year she took acourse in abnormalpsychology from WilliamBlatz, a psychologistwhosesecuritytheoryheldthat a young child’s senseofwell-being derives from

proximity to his parentsandthatthechild’sabilityto grow and developdepends on the constancyofhisparents’availability.DrawntoBlatzbyherownabidingsenseofinsecurity,Ainsworth went on to dograduate work inpsychology, eventuallybecoming, in 1939, alecturer in the Universityof Toronto’s psychology

department. Butwhen herhusbanddecided toattendgraduate school inEngland, she had to findwork in London. A frienddirected her to anadvertisement in TheTimes, placed by apsychoanalyst seekingresearch help on a projectabout the developmentaleffects of early childhoodseparation from the

mother. Keen tounderstand herrelationship with her ownmother, who had beenself-absorbed and distant,Ainsworth applied. JohnBowlby hired her—andwiththatbeganthecentralpartnership in thedevelopment ofattachmenttheory.Ainsworth made two

signature contributions to

the field. The first was inthe mid-1950s, when sheaccompanied her husbandto Kampala, Uganda. InKampala, Ainsworthidentified twenty-eightunweaned babies fromlocal villages and beganobserving them in theirhomes, studyingattachment behavior in anatural environment. Shekept meticulous records,

tracking breast-feeding,toilet training, bathing,thumb sucking, sleepingarrangements, expressionsof anger and anxiety, anddisplays of happiness andsadness, and she watchedhow the mothersinteracted with thechildren. It was the mostextensive naturalisticobservationofthissortyetconducted.

When Ainsworth firstarrived in Uganda, sheagreed with both theFreudians and thebehaviorists that theemotional attachmentbabies invested in theirmothers was a secondaryassociation with feeding:mothers provided breastmilk, which providedcomfort,sobabiescametoassociate that feeling of

comfort with the mother;therewasnothinginherentin the maternalrelationship itself, distinctfromtheprovisionoffood,that was psychologicallysignificant. But asAinsworth totted up hermeticulous observations,shechangedhermind.TheFreudiansandbehavioristswere wrong, sheconcluded, and Bowlby

wasright.Whenthebabiesbegan to crawl on theirown and to explore theworld around them, theywouldrepeatedlyreturntotheir mothers—eitherphysically or byexchanging a reassuringglance and a smile—andappearedalwaystoremainconsciousofexactlywheretheir mothers were.Describing what she

observed when the babiesfirst began to crawl,Ainsworth wrote that themothersseemedtoprovidethe “secure base” fromwhichtheseexcursionscanbe made without anxiety.The secure basewould goon to become a crucialelement of Bowlby’sattachmenttheory.Ainsworth noticed that

whereassomebabiesclung

fiercelytotheirmothersatalmost all times and criedinconsolably whenseparated from them,others seemed indifferent,tolerating separationswithout evident distress.Did this mean that theuninterested babies lovedtheirmotherslessthantheclinging babies and weresomehow less attached tothem? Or, as Ainsworth

came to suspect, did thismean that the clingingbabieswereinfactthelesssecurelyattachedones?Ainsworth ultimatelydeemed seven of thetwenty-eight Ugandanbabies “insecurelyattached.” She studiedthemcarefully.Whatmadethem so anxious andclingy? For themost part,these insecure babies

seemed to receive thesame quantity ofmaternalcareastheotherones;theinsecure babies had notsuffered inordinate ortraumatic separations thatwould explain theiranxiety.Butas she lookedmore closely, Ainsworthbegan to notice thingsaboutthemothersoftheseinsecure babies: some ofthem were “highly

anxious,” distracted bytheir own preoccupations—often they had beendesertedbytheirhusbandsor had disordered familylives.Still,shewasn’tableto point conclusively tospecific maternalbehaviors that generatedseparation anxiety orinsecureattachment.In 1956, Ainsworth

movedtotheUnitedStates

and began teaching atJohns Hopkins.Determined to find outwhether attachmentbehaviors were culturallyuniversal, she decided tocontrive an experimentthatcouldtestthis.Thus was born what

Ainsworth called thestrange situationexperiment, which hasbeen a staple of child

developmentresearcheversince. The procedure wassimple.Amotherandchildwould be placed in anunfamiliarsetting—aroomwith a lot of toys in it—and the baby would befreetoexplore.Then,withthemother still present, astranger would enter theroom. How would thebaby react? Then themother would exit the

room, leaving the babywith the stranger. Howwould the baby react tothat? Then the motherwould come back. Howwouldthebabyrespondtothereunion?Thiscouldberepeated without thestranger—the motherwould leave the childaloneintheroomandthenreturnawhilelater.Allofthiswouldbeobservedby

researchers sitting behinda two-way mirror. Overthe ensuing decades,thousandsofrepetitionsofthis experiment producedmountainsofdata.Theexperimentsyieldedsome interesting insights.In the first phase of theexperiment, the babieswould explore the roomandlookat the toyswhilechecking in frequently

with the mothers—suggesting that babies’psychological need tooperate from a “securebase” is indeed universalacrosscultures.Butbabiesvaried a lot in howdistressed they wouldbecome when separatedfrom their mothers: abouthalf of them cried aftertheir mothers left theroom, and some babies

becameseverelydistressedand had a hard timerecovering. When theirmothers returned, thedistressed babies wouldbothclingtoandhitthem,displaying both anger andanxiety.Ainsworthlabeledthese insecure babies“ambivalent” in theirattachment. Even morefascinating to Ainsworththantheambivalentbabies

were those she wouldcome to label “avoidant”in their attachment style:these babies seemedcompletely indifferent totheir mothers’ departuresand rarely got perturbed.Superficially, they seemedquite healthy and welladjusted. But Ainsworthwould come to believe—and a lot of researchwould eventually be

produced to support theidea—that theindependence andequanimity these avoidantbabies displayed were infact the product of adefense mechanism, anemotional numbingdesigned to cope withmaternalrejection.As Ainsworth collectedher data, the most tellingfact to emerge was the

powerful correlationbetween a mother’sparenting style and herchild’s general level ofanxiety. Mothers of thechildren identified byresearchers as securelyattached were quicker torespond to their children’ssignals of distress, tendedto hold and caress theirchildren for longer, andderived more apparent

pleasure from doing sothan did the mothers ofthe ambivalent andavoidant children. (Themothers of securelyattached children didn’tnecessarily interact morewith them, but theyinteracted better, beingmore affectionate andresponsive.) The mothersof the avoidant childrendisplayed the most

rejecting behavior; themothersof theambivalentchildren displayed themost anxiety and also byfar the mostunpredictability in theirresponses to theirchildren—sometimes they wereloving, sometimesrejecting, sometimesdistracted. Ainsworthwould laterwrite that thepredictability of maternal

response helped dictate achild’sconfidenceandself-esteem later in life; thosemothers who predictablyresponded to distresssignals quickly andwarmly had calmer,happier babies whobecame more confident,independentchildren.Over the next few

decades, the connectionbetween attachment style

and psychological healthwas repeatedly confirmedby a host of differentmeasures.g A series ofinfluential longitudinalstudies begun byresearchers at theUniversityofMinnesotainthe1970shavefoundthatsecurely attached childrenare happier, moreenthusiastic, and morepersistent and focused

when working onexperimental tasks thananxiously attachedchildren are and that theyhave better impulsecontrol. On almost everytest the researchersdevised, the securelyattached children didbetter than theambivalently attachedones:theyhadhigherself-esteem, stronger “ego

resiliency,” and lessanxiety and were moreindependent; they wereeven better liked by theirteachers. They alsodisplayed greater empathyfor others—probablybecause the insecurelyattachedchildrenweretooself-preoccupied to bemuch attuned to anyoneelse.Thesecurelyattachedchildren just seemed to

enjoy life more: none ofthe ambivalently attachedchildren smiled, laughed,orexpresseddelightatthesame level as the securelyattachedchildren.Manyofthe ambivalently attachedchildren tended to fallapart when subjected toevenminorstress.These effects persistedfor years, even decades.Teenagers who had been

securely attached astoddlers had an easy timemaking friends—but thosewho had beenambivalently attachedwere overwhelmed by theanxiety of navigatingsocial groups and oftenended up friendless andalienated. Studies foundthat adults with motherswho had ambivalentattachment styles tended

to procrastinate more, tohave more difficultyconcentrating, to be moreeasily distracted byconcerns about theirinterpersonal relations,and—perhapsasaresultofall this—to have loweraverage incomes thanthose with mothers whohad either secure oravoidant attachmentstyles. Many studies from

the last thirty years havesuggested that insecureattachment as a baby andyoung child is highlypredictive of emotionaldifficulty as an adult. Atwo-year-old girl with anambivalent attachment toher mother is on averagemuch more likely tobecome an adult whoseromantic relations areplagued by jealousy,

doubt, and anxiety; shewill always be seeking—likelywithoutsuccess—thesecure, stable relationshipthatshedidnothavewithher mother. The daughterof an anxious and clingymother will herself likelygrow up to be an anxiousandclingymother.

A mother who, due toadverse experiences

during childhood,grows up to beanxiously attached ispronetoseekcarefromher own child andthereby lead the childto become anxious,guilty, and perhapsphobic.—JOHNBOWLBY,ASecureBase(1988)

During the postwardecades, neurochemicalresearch woulddemonstrate thatwhen aninfant or an adult isstressed,acascadingseriesof chemical reactions inthebrainproducesanxietyand emotional distress;returning to a secure base(the mother or a spouse)releases endogenousopiates that make the

individual relax and feelsafe. Why should this beso?Backinthe1930s,John

Bowlby, already absorbedin his studies of themother-child bond,discoveredtheworkoftheearlyethologists.Ethology,the scientific study ofanimalbehavior,suggestedthat many of theattachment behaviors

Bowlby had beenobserving inhumanswereuniversal to all mammals,and it supplied anevolutionary explanationforthesebehaviors.The evolutionarily

adaptive benefit of earlyattachment behaviors isnothardtofigure:holdingoffspring near helps amother to keep them safeuntil they are fit to fend

forthemselves.Thusitwaspossible, Bowlby realized,to explain separationanxiety almost purely interms of natural selection:there’s an adaptive valueto psychologicalmechanisms thatencourage mothers andchildren of whateverspecies to stick close toone another by producingdistress when they are

separated; those childrenmost predisposed to clingto their mothers in timesof distress may gain aDarwinian advantage overtheirpeers.In yanking the sources

ofanxietyoutoftherealmof fantasy and into theworldofethology,Bowlbyalienated hispsychoanalyticcolleagues.hWhenBowlby

first presented hisemergingresearchfindingsintheearly1950s,hewasattacked from two sides—by the psychoanalysts andthe behaviorists. For thebehaviorists, the mother-childbondhadnoinherentimportance; its relevanceto separation anxietyderived from the“secondary gains”—theprovision of food, the

soothing presence of thebreast—that the childcame toassociatewithhismother’spresence.For thebehaviorists, anattachment wouldn’t evenexist distinct from thespecific needs—mainly forfood—that the mothermet. Bowlby disagreed.Attachment behaviors—and separation anxiety—were biologically

hardwired into animals,including humans,independent of theassociation between foodandmothers.Indefenseofthis argument, Bowlbycited Konrad Lorenz’sinfluential 1935 paper“The Companion in theBird’s World,” in whichLorenz had revealed thatgoslings could becomeattached to geese, and

sometimeseventoobjects,thatdidnotfeedthem.iFreudians argued that

Bowlby’s reliance onanimalmodelsofbehaviorgave short shrift to theintrapsychic processes—suchasthebattlebetweenthe id and superego—thatset the humanmind apartfromotheranimals’.Once,after Bowlby presented anearly paper on separation

anxiety to the BritishPsychoanalyticSociety,theorganization dedicatedmultiple subsequentsessions to thepresentations of all thecritics who wanted to“bash” him. There werecalls to “excommunicate”himforhisapostasy.As psychoanalytic

criticism of Bowlbyswelled, he received a

bracing injection ofsupport from theworld ofanimal research when, in1958, Harry Harlow, thepresident of the AmericanPsychological Associationand a psychologist at theUniversity of Wisconsin,publishedanarticle in theAmerican Psychologistcalled “The Nature ofLove.” In it, Harlowdescribed the series of

experiments that are nowa fixture of everyintroductory psychologycourse.The experiments came

about by happenstance.Many of the rhesusmonkeys in Harlow’s labhad been contracting fataldiseases, so he took sixtyinfantmonkeys from theirmothers a few hours afterbirth to be raised in a

germ-free environment. Itworked: the separatedmonkeys stayed free ofdisease, and theirphysicaldevelopment seemednormal, even though theyremained apart from theirmothers. But Harlowobserved some strangethings about theirbehavior. For one, theyclung desperately to thecloth diapers used to line

the cage floors. Thosemonkeyswhowereplacedin mesh cages withoutdiapersseemedtostrugglephysically to survive; theydidbetter if given ameshcone covered in terrycloth.This gave Harlow an

ideaforhowhemighttesta hypothesis that he, likeBowlby,hadalways foundsuspect: the notion,

advanced by both thepsychoanalysts and thebehaviorists, that a babybecomes attached to hismother only because shefeeds him. Even grantingthat the mother’sassociationwith foodmayprovide a “secondary-reinforcing agent” (inbehaviorist terminology),Harlow didn’t think thatthose early feedings were

enough to account for thematernal bond—the loveand affection—thatpersisted for decadesafterward. Could hisseparated rhesusmonkeys,Harlowwondered,beusedtoresearchtheoriginsofachild’s loveofhismother?Hedecidedtotry.He separated eight

rhesus babies from theirmothers and placed each

initsowncage,alongwithtwocontraptionshecalledsurrogatemothers. One ofthe two mothers in eachcage was made of wiremesh; theotherwasmadeof wood but was coveredwithterrycloth.Infourofthe cages, a rubber nippleoffering milk was affixedto the mesh surrogate; inthe other four, the nipplewas affixed to the cloth-

covered one. If thebehaviorist suppositionwas correct andattachment was merely aby-product of associationwith feeding, then theinfantsshouldalwayshavebeen drawn to thesurrogate possessing thenipple.That’s not whathappened. Instead, alleight monkeys bonded

with the cloth mother—and spent sixteen toeighteen hours a dayclinging to it—even whenthewiremotherprovidedthefeeding nipple. This was adevastating blow to thebehaviorist theory ofseparation anxiety. If themonkeysweremore likelyto bond with a soft andcuddly object that didn’tfeedthemthanwithawire

one thatdid, hunger reliefcouldnotbetheoperativeassociation in thebondingprocess,asthebehavioristshadassumed.jBy coincidence, Bowlby

attended the AmericanPsychological Associationmeeting in Monterey,California, where Harlowfirstpresentedhis “Natureof Love” paper. Bowlbyimmediately recognized

the relevance of Harlow’swork to his own, and thetwo men made commoncause. In the ensuingyears, other studieswouldreplicate Harlow’s initialfindings. For Bowlby, thiswas vindication, armoragainst the assaults of theFreudians and thebehaviorists. “Thereafter,”Bowlbywould laterwrite,“nothing more was heard

of the inherentimplausibility of ourhypotheses; and criticismbecame moreconstructive.”TheHarlowstudywould

prove even more relevantto Bowlby’s ideas aboutattachment relationshipsthan either man knew atthetime.Inlateryears,themonkeys from Harlow’sinitial study suffered

lasting effects from theseparation experiment. Asintenselyasthebabieshadseemed to bond with theinanimateclothsurrogates,this was clearly noreplacement for a realmother-child relationship:for the remainder of theirlives, these monkeys hadtrouble relating to theirpeers and exhibitedabnormalsocialandsexual

behavior. They wereabusive, even murderous,parents. When presentedwithnoveltyorstress,theybecame much moreanxious, inhibited, andagitated—which is exactlywhatBowlbyhadobservedin his studies of humanswho had enduredseparations or difficultrelations with theirmothers. All of this was

haunting confirmation ofthe long-term effects ofearly experiences withseparation andattachment.kIn the ensuing decades,

hundreds of other animalexperiments havesupported these findings.Robert Hinde, anethologist at CambridgeUniversity, showed thatwheninfantmonkeyswere

separated from theirmothers for only a fewdays, theywere stillmoretimid than controlmonkeyswhenplacedinanovelsituationfivemonthslater. A subsequent paperbyHarryHarlowobservedthat certain key maternalstyles—suchas “near totalacceptance of her infant(the infant can do nowrong)” and close

supervision of the infant’s“beginning sallies beyondher arm’s reach”—werepredictive ofwell-adjustedadult monkeys. Recentstudies of rhesus monkeyshave found that the“initiation of ventralcontact” (or hugging, inplain English) reducessympathetic nervoussystem arousal; thosemonkeys that received

fewer hugs from theirmotherswerelesslikelytoexploretheenvironment—and were more likely todisplay anxious ordepressive behavior asadults. In other words,when monkey motherscoddled and protectedtheir babies, those babiesgrew up healthy andhappy—which is preciselywhat Mary Ainsworth

noted in her meticulouslong-term observations ofmother-infant interactionsamonghumans.

Remember when youaretemptedtopetyourchild that mother loveis a dangerousinstrument.—JOHNWATSON,

PsychologicalCareof

InfantandChild(1928)

The experiments ofHarlow, Hinde, and theircontemporaries had beenfairly crude; theseparations they forcedwere severe, and thesituationstheysetupwerenot analogous to real life.But in 1984, a group ofresearchers at Columbia

University devised a wayof approximating moreclosely the range ofseparationandattachmentbehaviorsthatoccurinthewild.The idea behind the

variable foraging demand(VFD) paradigm, as theresearchers called it, wasthat changing theavailabilityofthemother’sfoodsupplycouldproduce

changes in the way sheinteracted with heroffspring. (Primatologistsalready knew this fromextensive observations inthe wild.) In what havebecome known as VFDexperiments, researchersmanipulate how easy orhard it is for monkeymothers to get food:during low-foraging-demand periods, food is

left freely exposed incontainers strewn aroundthe primates’ enclosure;during high-foraging-demand periods, food ismore difficult to get,buried in wood chips orhiddenundersawdust.Inatypical VFD experiment, atwo-week period duringwhich food is easy to findis followedbya two-weekperiod when it’s hard to

find.Unsurprisingly, the

mothersaremorestressed,and less available to tendto their offspring, duringhigh-foraging-demandperiods than they areduring low-foraging-demand periods. Bonnetmacaques whose mothersare subjected to extendedhigh-foraging-demandperiods have, on average,

more social and physicalproblems growing up. Butepisodes of variableforaging demand turn outto be even more stressfulthan extended high-foraging-demandperiods—that is, the mothers aremorestressedwhenfoodisunpredictably unavailablethan when it isconsistentlyhardtofind.Jeremy Coplan, the

director ofneuropsychopharmacologyatStateUniversityofNewYork Downstate MedicalCenter, has beenconducting VFDexperiments for fifteenyears. He says that theseexperiments appear toinduce a “functionalemotional separation”between mother andinfant.Thestressedmother

becomes “psychologicallyunavailable” toher infant,inthewaythatastressed-out human mother (likeAmalia Freud) mightbecome distracted andinattentivetoherchildren.The shifts in behavior

might appear subtle—thestressed mothers stillrespondtothebabies,theyjust tend to do so moreslowly and less effectively

than the unstressedmothers—but the effectscan be potent. In a seriesof experiments, Coplanand his colleagues foundthat the children of theVFD mothers had higherlevels of stress hormonesin their blood than thechildren of the non-VFDmothers—an indicationthat the mother’s anxietywas being transmitted to

the child. The remarkablething was the duration ofthe correlation betweenthe mother’s anxiety andthe child’s stresshormones: when Coplanexamined those originalVFD children ten yearsafter the first experiment,their levels of stresshormoneswerestillhigherthan those of a controlgroup. When they were

injected with anxiety-provokingchemicals, theirresponses werehyperreactive comparedwith other monkeys’.Evidently, these VFDmonkeys had becomepermanently moreanxious: they were lesssocial, more withdrawing,andmore likely todisplaysubordinatebehavior;theyalso showed an elevated

levelofautonomicnervoussystem activity and acompromised immuneresponse. Here waspowerful physiologicalevidence of what Bowlbyhad argued half a centuryearlier: early child-rearingexperiences—not just theobviously traumatic onesbut subtle ones—havepsychologicalandphysicaleffectsonthewell-beingof

the child that persist eveninto adulthood. Coplan’steam concluded that evenbrief disruptions in themother-child relationshipcan alter the developmentof neural systems “centralto the expression of adultanxietydisorders.”lVersions of this

experimentrepeatedmanytimes over the last twentyyears have continually

foundsimilar results:briefperiods of childhoodstress, and even mildstrainsonthemother-childrelationship, can havelasting consequences on aprimate’sneurochemistry.m There’seven some evidence thatthe grandchildren of theVFD mothers will haveelevated cortisol levelsfrombirth,astheeffectsof

those brief early weeks ofmildstressget transmittedfrom generation togeneration.Researchers have found

analogous evidence in thedescendants of traumavictims: the children andeven grandchildren ofHolocaust survivorsexhibit greaterpsychophysiologicalevidence of stress and

anxious arousal—such aselevated levels of variousstress hormones—than doethnically similar childrenand grandchildren ofcohorts who were notexposed to the Holocaust.When these grandchildrenareshownstressfulimageshaving nothing directly todowiththeHolocaust—forinstance, of violence inSomalia—they display

more extreme responses,both in behavior andphysiology, than do theirpeers.AsJohnLivingstone,a psychiatrist whospecializes in treatingtrauma victims, told me,“It’s as though traumaticexperiences get plasteredintothetissuesofthebodyand passed along to thenextgeneration.”Bynowscoresofstudies

support the idea that thequantity and quality of amother’s affection towardher children has a potenteffect on the level ofanxietythosechildrenwillexperience later in life. Arecent study published intheJournalofEpidemiologyand Community Healthfollowed 462 babies fromtheir birth in the early1960s in Providence,

Rhode Island, throughtheirmidthirties.Whenthestudy subjects wereinfants, researchersobservedtheir interactionswith their mothers andratedthemothers’ levelofaffection on a scalerangingfrom“negative”to“extravagant.” (Mostmothers—85 percent ofthem—wererated“warm,”or normal.) When

psychologists interviewedthe study subjects thirty-four years later, thosewhosemothershadshownaffection that was“extravagant” or“caressing” (the secondhighest level) were lesslikely to be anxious or toexperience psychosomaticsymptomsthantheirpeers.This would seem to

suggest that John Bowlby

was right—that if youwant to raise a well-adjusted, nonanxiouschild, thebestapproach isnot the one prescribed bythe ur-behaviorist JohnWatson,whoonceaverred,“Remember when you aretempted to pet your childthat mother love is adangerous instrument.” Inhis famous 1928 book onchild rearing, Watson

warned that a mother’saffection could havedangerous effects on achild’s developingcharacter. “Neverhugandkiss them, never let themsit in your lap,” hewrote.“If you must, kiss themonceontheforeheadwhentheysaygoodnight.Shakehands with them in themorning. Give them a paton the head if they have

made an extraordinarilygood job of a difficulttask.” Treat children, inother words, “as thoughthey were young adults.”Bowlby, who had himselfbeentreatedthatwayasaboy,believedmoreor lessthe opposite: if you wantto instill a secure base inthe child and a resistanceto anxiety and depression,be unstinting in the

provision of love andaffection.

By 1973, when hepublished his classicSeparation: Anxiety andAnger, Bowlby wasconvinced that almost allformsofclinicalanxietyinadultsn could be traced todifficult early-childhoodexperiences with the

primary attachment figure—almost always themother. Recent researchcontinues to add to thesubstantialpileofevidencesupporting this idea. In2006,newresultsfromtheforty-year longitudinalMinnesota Study of RiskandAdaptation fromBirthto Adulthood found thatinfants with insecureattachments were

significantly more likelythaninfantswithsecureoravoidant attachments todevelop anxiety disordersas adolescents. Insecureattachment in infancyleads to fears ofabandonment in laterchildhood and adulthoodand gives rise to a copingstrategybasedon“chronicvigilance”—those babieswho anxiously scan the

environment to monitorthe presence of theirerratically availablemothers tend to becomeadults who are foreveranxiously scanning theenvironment for possiblethreats.Bowlby’s attachment

theory has an elegantsimplicity and a plausible,easily understoodevolutionary basis. If your

parents provided a securebase when you were aninfant and you were ableto internalize it, then youwill be more likely to gothrough life with a senseofsafetyandpsychologicalsecurity. If your parentsfailedtoprovideone,oriftheydidprovideonebutitwas disrupted by traumaorseparation,thenyouaremorelikelytoendurealife

ofanxietyanddiscontent.

Theyfuckyouup, yourmum anddad.

Theymay notmean to,buttheydo.

—fromPHILIP

LARKIN,“THISBETHE

VERSE”(1971)

I recentlycameacrossadiary that Ikeptbriefly inthesummerof1981,whenI was eleven years old.SomemonthsearlierIhadstarted seeing the childpsychiatrist who would

treat me for twenty-fiveyears, Dr. L., who wastrained as a Freudian. Athisinstigation,Iwasusingthe diary to free-associateinpursuitoftherootcauseofmyemotionalproblems.I must say it wassomewhat dispiriting formy early middle-aged selfto discover my eleven-year-old self already soanxious and self-absorbed,

wonderingonthepagesofthe journal which sourcebore greater responsibilityformyabidinganxietyanddiscontent: Was it thetyrannical camp counselorwho had, when I was six,yelledatmeandsentme—alone among the merrycampers of the Sachemtribe at the Belmont DayCamp—to the baby poolbecauseIwasshakingand

crying, afraid to get intothe big pool on my own?Or was it the neighborwhohad,whenIwasfour,slapped me in the face infront of all my preschoolpeers when I broke downinto hysterical sobs at thebirthday party for her sonGilbert because I wasscared and wanted mymommy?Evidently,mynarcissism

and quest for self-knowledge are endlesslyrecursive: I dig back intothepastatageforty-three,seeking the roots of myanxiety, anddiscover…myself, at ageeleven, digging back intothepast, seeking the rootsofmyanxiety.We had just returned

from a family vacation,and much of the diary is

an enumeration of thefears and perceivedinjusticesIhadenduredonthetrip.

1.Afraidofmotionsicknessonplane.

2.1stnighthomesickness,can’tsleep.

3.Don’tlikethefood.4.Restaurant:mummy

gettingmadandnottalkingtomebecauseIcomplainedaboutwantingtogohome.

5.Afraidofunsanitariness.

6.Afraidthinairinmountainswillmakemesick.

7.Daddyforcingmeto

eat.GettingmadwhenIeatandnotlettingmeeatwhenIcomplain…

8.Dadnotlisteningtome,andhittingmewhenIpersistedinasking.

9.IwasreallyscaredandupsetwhenIsawwhatmayhavebeenthrowupon

therugdownstairs.Ifeltawfulandscared.

10.Ontheplanerideback,personthrowsup.Iamterrified.Feelsad,depressed,andscared.

The trip diary ends: “Ijust feel like hiding myhead and being huggedand loved by mymummy

anddaddybuttheyarenotsympatheticaboutmyfearatall.”Notlongago,Ie-mailed

mymother a transcriptionof the diary and thencalledtoaskifshethoughtthat she had expressedmore or less affection formysisterandmethanherpeers had for theirchildren.“About the same,” she

said.Thenshe thought foramoment. “Actually,” shesaid, “I consciouslywithheldaffection.”Stunned, I asked her

why.“I thought it was for

yourowngood,” she said,andwentontoexplain.Her own mother, my

grandmother ElaineHanford, had expressedample affection for my

mother and her sister andhad always been presentfor them, physically andotherwise.Elainebuiltherlifearoundcateringtoherdaughters’ needs. Everydaywhenmymothercamehome from elementaryschool for lunch, Elainewas there to make it forher.Mymother felt lovedand cared for—andcoddled.And sowhen she

started to struggle withpanic attacks andagoraphobia andemetophobia and otherphobias as a young adult,shewonderedifmaybeheranxiety was so intensebecause she had felt tooloved and safe in hermother’sabundantcare.Soin an effort to spare mysister and me the anxietysheendured,shedeniedus

theoutwardexpressionsofunconditionalloveshehadreceived.John Watson wouldhaveapproved.But while my motherspared us affection, shedidn’t spare usoverprotection.Overprotection andwithheldaffectioncanbeapernicious combination. Itcan lead to feeling not

only unloved (becauseyou’re not receivingaffection) but alsoincompetent and helpless(because someone’s doingeverything for you andassuming you can’t do ityourself).My mother physicallydressed me until I wasnineortenyearsold;afterthat, she picked out myclothes formeeverynight

untilIwasfifteen.Sheranmy baths for me until Iwas in high school. Bymiddleschool,manyofmyfriendswere taking publictransportation todowntownBoston to hangout, staying home aloneduring school vacationswhiletheirparentswereatwork, and shopping for(and buying and riding)motorbikes. Even if I had

been inclined to take thesubway to Boston or toride motorbikes—and,believe me, I wasn’t—Iwouldn’t have beenallowed to: I wasn’tpermitted to walk morethan a few streets awayfrom our suburbanneighborhood becausethere were streets mymother deemed too busyto cross and

neighborhoodsshedeemedtoo dangerous to traverse.(Thisinasleepycommutersuburb where a violentcrime was a once-in-a-decade affair.) AnytimemysisterandIwerehomewhile my parents were atwork,wehadthecompanyofababysitter.BythetimeI was a young teenager,thiswasgettingabitweird—as I realized one day

when I discovered, to ourmutual discomfort, thatthebabysitterwasmyage(thirteen).My mother did all this

out of genuine anxiousconcern. And I welcomedthe excess of solicitude: itkept me swaddled in acomfortingdependency.Asembarrassing as it was tobe told in front of mypeers that I couldn’t walk

downtown with themunless my mother camewith us, I didn’twant herto relinquish herprotective embrace. Thedyad betweenmother andchild implicates thebehaviorofeach—Icravedoverprotection;sheofferedit. But our relationshipdeprived me of autonomyor a sense of self-efficacy,and so Iwas a clingy and

dependent elementaryschoolstudent,andthenaclingy and dependentteenager, and I then grewup to be—as my long-sufferingwifewilltellyou—adependentandanxiousadult.“Adults with

agoraphobia are morelikely to rate theirparentsas low on affection andhigh on overprotection.”

(That’sfroma2008paper,“Attachment andPsychopathology inAdulthood.”) “Adults withagoraphobia report morechildhood separationanxiety than a controlgroup.” (A 1985 studypublished inTheAmericanJournal of Psychiatry.)“[Infants with insecure]attachments [are]significantly more likely

than infants with secureattachments to bediagnosed with anxietydisorders.” (A 1997 studypublishedintheJournalofthe American Academy ofChild and AdolescentPsychiatry.) “Your parents—anxious, overprotectivemother and alcoholic,emotionally absent father—were a classicallyanxiety-producing

combination.”(That’sfrommy first psychiatrist, Dr.L., whom I recentlytracked down andinterviewed, nearly thirtyyears after my firstappointments with him.)And then there’s theneurobiological evidenceforallthis:“Humanadultswho reported extremelylow-quality relationshipswith their parents

evidenced significantlymore release of dopaminein the ventral striatum [aportion of subcorticalmaterial deep in theforebrain] and a higherincrease in salivarycortisol[astresshormone]during a stressful eventthan individuals whoreported extremely high-quality parental relations.Such an effect suggests

that early humancaregiving may similarlyaffect the development ofsystems that underliestress reactivity.” (A 2006study published inPsychological Science.) As Iwrite this, I have in myoffice a stack of articlesnearly two feet highreinforcing these andrelated findings. Whichproves that my anxiety is

largely a function of mychildhood relationshipwithmymother.Except,ofcourse,thatit

doesn’t prove anything ofthesort.

* The strong predictive associationbetweenachildhoodfearofdogsand adult dysfunction mightmeanthatadogphobiasomehowcauses later social phobia,

depression,ordrugaddiction.Orit might mean that a childhoodfearofdogsandadultdepressiontendtobeproducedbythesamekinds of environmentalcircumstances—an impoverishedinner-city childhood, say, wheredangerous pit bulls are a realthreatandwhereearlytraumaordeprivation can lay the neuralgroundwork for later depression.Or it might mean that a fear ofdogsandadultdepressionordrug

addictionaredifferentbehavioralmarkers of a shared geneticunderpinning—the same geneticcoding that predisposes you tofear dogs might also predisposeyou to depression. Or, finally,maybeachildhoodfearofdogsisactually the very same thing asadult panic disorder ordepression. That is, it might bethat childhood phobia and adultdepression are the same disease,unfolding over the life cycle

through different developmentalstages, each stage expressingdifferent symptoms. As I’venoted, specific phobias tend toappear early in life—half of allpeople who will ever have aphobiaintheirlivesfirstdevelopit between the ages of six andsixteen—soperhapsadogphobiais simply the first symptom of abroader disorder, theway a sorethroat can augur the onset of acold.

†AccordingtoFreud’stheoryoftheOedipuscomplex,aboy’sgreatestanxiety is that his father willcastrate him as punishment forsexuallydesiringhismother,anda girl’s greatest anxiety isgenerated by her envy of thepenis she lacks. Thiswas largelyderived from Freud’s ownrecollectionof,ashewroteFliess,“being in love with my motherandjealousofmyfather.”

‡ James Strachey, a British

psychoanalyst and translator ofFreud’s works, speculated thatFreud’s linking of childbirth andanxietydatedtotheearly1880s,when, while working as aphysician, he heard secondhandabout a midwife who haddeclared that there is a lifelongconnection between birth andbeingfrightened.

§ Rank believed the birth traumaexplained everything—fromterritorial conquests like

Alexander theGreat’s (motivatedby an “attempt to gain solepossession of the mother” fromthefather)torevolutionsliketheFrench (anattempt tooverthrow“masculine dominance” andreturn to the mother) to phobiaof animals (“arationalization … of the wish—through the desire to be eaten—to get back again into themother’swomb”) to theapostles’dedication to Jesus Christ (“they

could see in him one who hadovercome the birth trauma”).Some of Freud’s later discipleswould denounce Rank, notwithoutreason,asinsane.

‖ Most animals emerge from theuterus or the egg dependent tosome extent on parental care fortheirsurvival,butthemajorityofthem are relatively lessdependent than humans are atbirth.

a Freud did retain for

psychoanalysis someinterpretative élan by positingthat childhood phobias becomeoverly severe or persist intoadulthood only when theybecometheouterfears(ofratsorheightsordarknessorthunderoropen spaces—or mayonnaise, anoted phobia in the literature)onto which inner psychicconflicts get projected. Phobias,in this view, are the outwardsymbolic representations of the

threats that the id (with itswanton impulses that must berepressed)andthesuperego(withits strict demands of conscienceandmorality)placeontheego.

bRobertKarenobservesthatalmosteverything Bowlby wrote aboutthe needs of young childrenthroughouthislongcareer“couldbe seen as an indictment of thetypeofupbringingtowhichhe’dbeensubjected.”

c Born in Vienna and trained as a

nursery school teacher, Kleinwouldgoon,after theendofanunhappy marriage, to bepsychoanalyzedbytwoofFreud’sclosest disciples, Sándor Ferencziand Karl Abraham, and thenherself to becomeone of Freud’smost important followers andinterpreters.In1926,Klein,forty-fouryearsold,movedtoLondon,where shewas exalted byErnestJones, the head of the BritishPsychoanalytic Society and the

most ardent protector of Freud’slegacy. Klein’s arrival in London—and in particular herdisagreements with Freud’sdaughter Anna Freud over theanalysis and treatment ofchildren—precipitated a rift inthesocietybetweentheKleiniansand the (Anna) Freudians thatwouldlastthroughWorldWarII.

dInhisinitialworkonhysteria, inthe early 1890s, Freud hadargued that adult neuroses were

the product of actual earlychildhood traumas, mostly of asexual nature—but by 1897 hehad revised his view to supporthis emerging notion of theOedipus complex, arguing nowthat adult neuroses were theresult of repressed childhoodfantasies about having sex withthe opposite-sex parent andmurdering the same-sex parent.Adults without neuroses werethose who had successfully

worked through their Oedipuscomplexes; adults with neuroseswerethosewhohadn’t.

e Adult romantic relationshipsamong those with ambivalentattachment styles tend to becharacterized by clinginess andfearofabandonment.

fAdultavoidantstendtoshuncloserelationships and are oftenworkaholics; just as theypreferred their toys to theirmothers as children, they prefer

worktofamilyasadults.(Thoughthose with avoidant attachmentstyles appear to be less anxiousthan those with ambivalentattachment styles, Bowlby cametobelievethatwasnotthecase;aseriesof studiesbeginning in the1970s have demonstrated thatduring separations the avoidantchildren exhibited increasedlevels of physiological arousal—elevated heart rates, increasedexcretion of stress hormones in

thebloodstream,andsoforth—ofthe sort associated with anxiety.The child seems to be feeling aphysically manifested distress,butheisable—adaptively,ornot—to suppress visible expressionoftheemotion.)

g As a result of Bowlby andAinsworth’s influence, by the1980s the psychologydepartments of Americanuniversities were thicklypopulated with attachment

scholars.

hDespitewhatFreudwrote late inhis life about the evolutionaryroots of phobic anxiety, hisconversiontothislineofthinkingcame too late to influence hisfollowers, who were nowspreading the gospel ofpsychoanalysis around theglobe.Through at least World War II,psychoanalytic theorists stillviewed castration fears, therepressive superego, and the

sublimated death instincts as the“cornerstones”—in Bowlby’sword—of anxiety. (Bowlbybelieved that if Freudhadhad afuller understanding of Darwin’swork,psychoanalysiswouldhavemore convincingly incorporatedbiological principles into itscorpus.)

i When Bowlby made a series ofpresentations,“TheNatureoftheChild’sTietoHisMother,”tohiscolleagues in the British

PsychoanalyticSocietyinthelate1950s, he tried to place himselfandhisworksquarelywithintheFreudian tradition. The reactionsagainst himwere harsh. “What’sthe use to psychoanalyze agoose?”thepsychoanalystHannaSegalwouldlaterask(channelingOgden Nash), mocking Bowlby’sresort to ethology. “An infantcan’t follow itsmother; it isn’t aduckling,” another analyst saiddismissively.

j There were other parallelsbetween the monkeys’ behaviorandwhatBowlbyhadobservedinhuman babies. When Harlowintroduced a new object intotheir cages, the monkeys wouldrush to the cloth mother inagitation and rub up against ituntiltheyfeltsoothed;aftertheycalmed down, they would beginto investigate and play with theobject,using theclothmotheras—to invoke the phrase that

Bowlby and Ainsworth wouldsoonbeusing—“asecurebase.”

kAs so often seems to be the caseacross the history of psychology,Harlow was unable to apply tohisownlifewhathelearnedfromhis research on parent-childrelationships: he died alcoholicanddepressed,estrangedfromhischildren.

l Related research on rodents findsthe same thing: the amount oflicking and grooming that a

mother rat lavishes on her pupshasapowerfuleffectonthepups’tolerance for stress throughouttheir lifetimes—the more lickingandgroominga rat receivesasapup,themoreresistanttostressitwillbeasanadult.Theratswhoreceive extra maternal lickingdisplay reduced autonomicnervous system activity—adiminishedlevelofactivityinthehypothalamic-pituitary-adrenalaxis—and a concomitant

increased tolerance for stress.Thesewell-licked rats havewhatresearchers call an “augmented‘off’ switch” for the stressresponse; after just four days ofextramaternallicking,theyshowreducedactivityintheamygdala.Incontrast,thoseratsthatreceivelow levels of maternal groomingexhibit an exaggerated stressresponse.

These effects can be adaptiveevenwhentheymightseemtobe

negative. Rats who as pupsreceived low levels of groomingand licking aremore fearful andquicker to learn to avoidfrightening environments—auseful adaptation in a harsh ordangerous environment. In fact,thatdangerousenvironmentmay,in the stateofnature,havebeenwhat produced the low levels oflicking and grooming in the firstplace, as the mothers werefocused on finding food or

avoiding external threats ratherthan on lavishing affection ontheir children. Rats who receivehigh levels of maternal affectionare less fearful, moreadventurous, and slower to learnto avoid threats—usefuladaptations in a stableenvironment but liabilities in adangerousone.

mNeuroscienceresearchhasbegunto find suggestive evidence forthespecificmechanismsbywhich

early life stress generates laterpsychopathology. In essence,elevatedlevelsofstresshormonesin childhood correlate withadverse effects on the brain’sserotoninanddopamine systems,which are strongly implicated inclinical anxiety and depression.Neuroimaging studies also showthat protracted childhood stresstendstohavewhatscientistscallneuropathological consequences:for instance, the hippocampus, a

part of the brain crucial tocreatingnewmemories,shrinks.

nTheexceptionwasspecificanimalphobias, which Bowlby, likeFreud, believed came fromevolutionary adaptations goneawry.

CHAPTER9

WorriersandWarriors:The

GeneticsofAnxiety

The manner andconditions ofmind are

transmitted to thechildren through theseed.—HIPPOCRATES(FOURTH

CENTURYB.C.)

Such as thetemperature of thefather is, such is theson’s, and look whatdisease the father hadwhenhebegothim,his

sonwillhaveafterhim.I need not thereforemake any doubt ofmelancholy, but that itis an hereditarydisease.—ROBERTBURTON,The

AnatomyofMelancholy(1621)

Daddy,I’mnervous.—MYDAUGHTER,ATAGE

EIGHT

I could blithely blamemyanxietyonthebehaviorofmy parents—my father’sdrinking, my mother’soverprotectiveness andphobias, their unhappymarriage and eventualdivorce—were it not for,among other reasons, this

inconvenient fact: mychildren,nownineandsix,have recently developedanxiety that, to adistressing degree,parallelsmyown.My daughter, Maren,

has always had, like me,an inhibited temperament—shy and withdrawing inunfamiliar situations, riskaverse in her approach tothe world, and highly

reactive to stress or anykind of novelty. Morestrikingly,whenshewasinfirst grade she developedan obsessive phobia ofvomiting. When aclassmateofhersthrewupduring math, she couldn’tget the image out of herhead.“Ican’tstopthinkingbad thoughts,” she said,andmyheartbroke.Have I—despite my

decades of therapy, myhard-won personal andscholarly knowledge ofanxiety,mywife’sandmyinformed efforts atinoculating our childrenagainst it—bequeathed toMarenmydisorder,asmymother bequeathed it tome?Unlike my mother, Inever revealed myemetophobia to my

daughter before shedevelopeditherself.Ihavetried not to betrayevidence ofmy anxiety toMaren,knowingthattodosomightbetopassitontoher through whatpsychologists callmodeling behavior. Mywife is not an anxiousperson;shehasnoneofthenervously overprotectivetendencies that, expressed

for so many years by mymother, I had thoughtreducedmy sister andmeto such states of neuroticdependency. And we areboth,mywifeandI,lovingand nurturing, and westrive to be emotionallypresent for our kids inways that my parentssometimeswerenot.Orsoweliketothink.And yet here is my

daughter exhibitingsymptoms very similar tomine and at almost thesameage I firstdevelopedthem. Somehow, despiteour best efforts atproviding emotionalprophylaxis, Maren seemsto have inherited mynervous temperament—and, remarkably, the exactsame phobic preoccupation.Which happens to be,

moreover,apreoccupationIsharewithmymother.Is it possible, my wife

asks, that so idiosyncratica phobia can begeneticallytransmitted?One would think not.

And yetwe have here theevidence of threegenerations on mymother’s side with thesame phobia. And unlessMaren has picked up on

subtleorunconsciouscues(which, I concede, ispossible), she cannot have“learned” the phobia fromme through some kind ofbehavioralconditioning,asI thought I might havelearned mine from mymother.While observers since

Hippocrates have notedthat temperaments areheritable, and while the

modernfieldofbehavioralgenetics is revealing withincreasing precision—down to the individualnucleotide—therelationship between themolecules we inherit andthe emotions we’repredisposedto,noonehasyet identified a gene, oreven a set of genes, foremetophobia.Nor,forthatmatter, has anyone

reduced anxiety—or anybehavioral trait—to puregenetics. But in recentyears,thousandsofstudieshave pointed to variousgenetic bases for clinicalanxiety in its differentforms.Some of the earliest

researchonthegeneticsofanxiety studied twins. Inthe most basic studies,researcherscomparedrates

of anxiety disorderbetween sets of identicalandfraternaltwins.If,say,panic disorder werecompletely genetic, thatwould mean in a set ofidentical twins—geneticcopies—you would neverfind just one with thedisease. But that’s not thecase. When one twin hasthe disorder, the other ismuch more likely than a

randomly selected personfrom the population tohave the disease—but notguaranteed tohave it.Thissuggests that while panicdisorder—like height oreye color—has a powerfulgenetic component, thedisease is not completelygenetic.In 2001, Kenneth

Kendler, a psychiatrist atVirginia Commonwealth

University, compared therates of phobic disordersamong twelve hundredsets of fraternal andidentical twins,determining that genesaccount for about 30percent of the individualdifferencesinvulnerabilityto anxiety disorders.Subsequent studies havetended to roughly supportKendler’s findings. Meta-

analysesof genetic studiesconclude that if you don’thave any close relativeswith generalized anxietydisorder, your odds ofhaving it yourself are lessthan one in twenty-five—but having a single closerelative with the disorderboosts your odds ofdeveloping it to one infive.Wait, you might object,

this doesn’t prove agenetic basis for anxiety.Couldn’t the highprobability of the samemental illnessoccurringinmembers of the samefamily be a result of theirsharing what researcherscall a pathogenicenvironment, one that ispredictive of anxiety ordepression? If twins sharea traumatic upbringing,

mightn’t that engender inboth of them a highersusceptibility to mentalillness?Certainly. While genesmaypredisposeapersontoschizophrenia oralcoholism or anxiety,there is almost alwayssome environmentalcontributiontothedisease.Still,thenumberofstudieson the heritability of

anxiety is climbing intothe tensof thousands,andthe overwhelmingconclusionofalmostallofthem is that yoursusceptibility to anxiety—both as a temperamentaltendency and as a clinicaldisorder—is stronglydeterminedbyyourgenes.This would not havesurprised Hippocrates orRobert Burton or Charles

Darwin or any number ofobservers who longpredate the era ofmoleculargenetics.Onceafamilytreehasoneortwoindividuals with anxietydisorder or depression,then you will likely findtherestofthetreestippledwith anxiety anddepression. Researcherscall this phenomenon“familial aggregation due

togeneticrisk.”*Does “familial

aggregation” mean thatmy daughter, like mymother and me, isbiologically predestined tobe anxious, perhapsgenetically fated todevelop nervous illness?Onmymother’ssideofthefamily alone, there is, inadditiontomymotherandmy daughter and me, my

son, Nathaniel, now six,who has separationanxiety that threatens tobecome as bad as mineever was; my sister, whohas struggled since agetwelve with anxiety andhas tried as many drugtreatments as I have;anotherbloodrelativewhohas similarly wrestled hiswhole life with anxietyand depression and a

nervous stomach andwhohas been medicated offand on for decades; thatrelative’s older brother,who was diagnosed withclinical depression in theearly 1980s, at the tenderage of eight, and whovomited from anxietybefore schoolnearlyeveryday for a year; and mymother’s father, ninety-two years old, who today

takes a variety ofantianxiety andantidepressantmedications. Lookingfurther back into myancestry,Ihavediscoveredthat my mother’s father’sgrandfather was painfullyreservedandhateddealingwith people, dropping outofCornelltostarta“quietlife” cultivating fruitorchards (“The outdoor

life saved him,” hisdaughter-in-lawwould saylater), and that mygrandfather’sauntsufferedfrom severe anxiety,depression,andafamouslynervousstomach.And then there is mygrandfather’s fatherChester Hanford, whoseanxiety and depressionwere severe enough thathe had to be

institutionalized multipletimes, leaving himfrequently incapacitatedduringthelastthirtyyearsofhislife.

Isuspectthatmost,butnot all, of the largenumber of humantemperaments are theresultofgeneticfactorsthat contribute to theprofiles of molecules

and receptor densitiesthat influence brainfunction.—JEROMEKAGAN,WhatIsEmotion?(2007)

It frequently happensthat hysteria in themother frequentlybegets hysteria in theson.—JEAN-MARTIN

CHARCOT,LecturesonDiseasesoftheNervousSystem,VOLUME3

(1885)

Jerome Kagan, adevelopmentalpsychologist at Harvard,has spent sixty yearsstudying the effect ofheredity on humanpersonality.Inlongitudinalstudies extending across

decades, he hasconsistently found thatabout 10 to 20 percent ofinfants are, from the timethey are a fewweeks old,demonstrably more timidthan other infants. Theseinfants are fussier, sleepmore poorly, and havefaster heart rates, moremuscletension,andhigherlevels of cortisol in theirblood and of

norepinephrine in theirurine. They exhibit fasterstartle reflexes (meaningthat in response to asudden noise they twitchnanoseconds faster andshow greater increases inpupil dilation). In fMRIscans, the fear circuits oftheir brains—namely, theamygdalaand theanteriorcingulate—show higher-than-normal neuronal

activity. Thesephysiological measuresremain consistently higherfor thesechildren than forother children throughouttheir lifetimes. Whetherthey are tested at sixweeks, seven years,fourteenyears, twenty-oneyears, or older, theycontinue to have higherheart rates, faster startlereflexes, and more stress

hormones than their low-reactivepeers.Kagan has labeled as

inhibitedthetemperamentof these children withhigh-reactive physiology.“We believe that most ofthechildrenwerefertoas‘inhibited’ belong to aqualitatively distinctcategory of infants whowere born with a lowerthreshold for arousal to

unexpectedchanges in theenvironment or novelevents,” Kagan says. “Forthese children, theprepared reaction tonovelty that ischaracteristic of allchildrenisexaggerated.”A few years ago, Kagan

and his colleagues tookbrain scans of a group oftwenty-one-year-olds theyhad been studying for

nineteen years. In 1984,when Kagan had firstobserved these subjects astwo-year-olds, he haddescribed thirteenof themas inhibited and the othernine as uninhibited. Twodecadeslater,whenKaganshowed pictures ofunfamiliar faces to alltwenty-two test subjects,now young adults, thethirteen who had been

identified as inhibiteddisplayed significantlymore amygdala responsethan the nine who hadbeen identified asuninhibited. Kaganbelieves that your genesdeterminethereactivityofyour amygdala—and weknow from other researchthat the reactivity of youramygdala, in turn, helpsdetermine how you will

reacttostress.Thoseinfantsortoddlersidentified as inhibited aremorelikelytobecomeshy,nervous adolescents—andthenshy,nervousadults—than their peers. They aremuch more likely todevelopclinicalanxietyordepression as teens oradults than their lessphysiologically reactivepeers. Even those high-

reactive babies who don’tgrow up to get officiallydiagnosed with anxietydisorders tend to remainmorenervous,onaverage,thantheirpeers.In believing thattemperamentisinnateandlargely fixed from birth,Kaganfallssquarelyintheintellectual tradition thatstretches back toHippocrates, who in the

fourth century B.C. arguedthat personality andmental health derivedfrom the relative balanceof the four humors in thebody:blood,phlegm,blackbile, and yellow bile.According to Hippocrates,as noted in chapter 1, aperson’s relative humoralbalance accounted for histemperament: whereassomeone with relatively

more blood might have alively or “sanguine”temperamentandbegivento hot-blooded explosionsof temper, someone withrelatively more black bilemight have a melancholictemperament.Hippocrates’s theory ofhumoral balance directlyanticipates,metaphoricallyanyway, the serotoninhypothesis of depression

andothermoderntheoriesof the relation betweenchemicalimbalancesinthebrain and mental health.For instance, Hippocratesattributed what we wouldby the mid-twentiethcenturybecallingneuroticdepression—and what wewould today callgeneralized anxietydisorder (DSM code300.02)—to an excess of

black bile (melain chole).As Hippocrates describedit, this condition wascharacterized by bothphysicalsymptoms(“painsat the abdomen,breathlessness … frequentburps”) and emotionalones (“anxiety,restlessness,dread…fear,sadness, fretfulness” oftenaccompanied and usuallycaused by “meditations

andworriesexaggeratedinfancy”).Hippocrates may havehadthewrongexplanatorymetaphor, but modernscience is proving him tohave been basically rightabouttemperament’sfixityand biological basis.Kagan,nowinhiseighties,is semiretired, but fourmajor longitudinal studiesstarted by him or by a

former protégé, NathanFox at the University ofMaryland, are still underway.All fourare reachingconclusions that supportKagan’s long-held theorythat the anxioustemperament is an innate,genetically determinedphenomenon thatcharacterizes a relativelyfixed percentage of thepopulation.† His studies

haverepeatedlyfoundthatthose 15 to 20 percent ofinfantswho react stronglyto strangers or novelsituations are much morelikely to grow up todevelop anxiety disordersthan their lessphysiologically reactivepeers. If you are bornhighly reactive andinhibited,youtendtostayhighly reactive and

inhibited. In decades oflongitudinal studies, onlyrarely has Kagan seenanyone move from onetemperamentalcategorytoanother.Allofwhichwouldseemto complicate, if notundermine, what I saidabout attachment theoryin the previous chapter.Indeed, Kagan believesJohn Bowlby, Mary

Ainsworth, and theircolleagues were largelywrong about how anxietygets transmitted from onegeneration to the next. InKagan’s view, insecureattachment style per sedoes not produce ananxiouschild.Rather—andI’moversimplifyingalittle—genes produce a motherwith an anxioustemperament; that

temperament, in turn,leads her to demonstratean attachment style thatpsychologistsobservetobeinsecure.Themother thentransmits this anxiety toher children—notprimarily, as Bowlby andAinsworth would have it,through her nervousparentingstyle(though,tobesure,thatmayintensifythe transmission), but

ratherbythepassingonofher anxious genes.Which,if true, would make itharder to break thetransmission of anxietyfrom generation togeneration throughchanges in parentingbehavior—and whichmightexplainwhy,despiteour best efforts, my wifeandIhavebeenunable toprevent our children from

developing signs ofincipientanxietydisorders.John Bowlby cited

animal studies to buttresshis theory of attachment.ButJeromeKagancanalsociteanimalstudiestorebutBowlby and support hisown theory oftemperament. In the1960s, researchers at theMaudsley Hospital inLondonbredwhatbecame

known as the Maudsleystrain of reactive rats,which responded to stresswith pronounced anxiousbehavior. These breedingexperiments wereperformed without thebenefit of moderngenomics. Researcherssimply observed ratbehavior, noted the“emotionally reactive”ones(mainlybymeasuring

their defecation rateswhen placed in openspaces), and mated themwith one another—and inso doing managed toproduce this highlyanxious strain. (By thesame selective breedingtechnique, they alsoproduced a strain ofnonreactive rats, whichresponded less fearfullythan average to open

spacesandotherstressors.)This seemed to beevidence of a potenthereditary component toanxietyinratpopulations.Modern experimental

techniques have advancedbeyond selective breeding.Scientists are now able tochemicallyswitchdifferentmouse genes on or off,allowing researchers toobserve how the genes

affect behavior. Bydeactivatingcertaingenes,researchers have createdmice that, for instance,nolonger experience anxiety,and in fact cannotrecognize real danger,because their amygdalaehave stopped working.Researchers, churning outhundredsofstudiesofthissort a year, have so faridentified at least

seventeengenes that seemto affect various parts ofthe fear neurocircuitry inmice.For instance, EricKandel, a Nobel Prize–winning neuroscientist atColumbia, has discoveredone gene (known as Grp)that seems to encode amouse’s ability to acquirenew phobias through fearconditioning and another

gene (known as stathmin)thatregulatesinnatelevelsof physiological anxiety.Mice whose Grp gene hasbeen switched off cannotlearntoassociateaneutraltonewithanelectricshockthe way normal mice do.Micewhosestathmingenehas been switched offbecomedaredevils:insteadof instinctively coweringontheedgeofopenspaces

like normal mice, theyventure boldly intoexposedareas.Evolution has conservedmany genes, so humansandrodentssharemanyofthe same ones. ConsiderRGS2, a gene that in bothmiceandhumansseemstoregulate the expression ofa protein that modulatesserotonin andnorepinephrine receptors

in the brain. After it wasnoted that mice withoutthe RGS2 gene displayedmarkedlyanxiousbehaviorand “elevated sympathetictone” (meaning theirbodies were on constantlow-grade fight-or-flightalert), a series of studieson humans by JordanSmoller and his team atHarvard Medical Schoolfound a relation between

certain variations of theRGS2 gene and humanshyness. In one study ofchildrenfrom119families,the kids who displayedcharacteristics of a“behaviorally inhibited”temperament tended tohave the same variant ofthe RGS2 gene. Anotherstudy, of 744 collegestudents, found thatstudents with the “shy”

variant of the gene weremore likely to describethemselves as introverted.Athirdstudyrevealedhowthe gene exerts its effecton the brain: when fifty-five young adults wereplaced in a brain scannerand shown pictures ofangry or fearful faces,those with the relevantRGS2variationweremorelikely to show increased

“neuronal firing” in theamygdalaandtheinsula,apart of the cortexassociated not only withlimbic system expressionsof fear but also with“interoceptive awareness,”that explicit consciousnessof inner bodily functionsthat can give rise to“anxiety sensitivity.” Afourthstudy,of607peoplewho lived through the

severe Florida hurricaneseasonof2004,foundthatthosewhohadtherelevantvariant of the RGS2 genewere more likely to havedeveloped an anxietydisorder in the aftermathofthehurricanes.None of these studiesprovethatsimplyhavingacertainvariantoftheRGS2gene causes anxietydisorder. But they do

suggestthattheRGS2geneaffects the functioning offear systems in the insulaand the amygdala—andthat individuals who havethe “shy” variant of thegene are more likely tohave hyperactiveamygdalae and toexperiencehigherlevelsofautonomic arousal insocial situations andtherefore to be shy or

introverted. (Shyness andintroversion are bothpredisposing factors in theanxietydisorders.)Lauren McGrath, a

researcher in thePsychiatric andNeurodevel-opmentalGenetics Unit atMassachusetts GeneralHospital, studied 134babies over nearly twentyyears. When the babies

were four months old,McGrath’s team dividedthemintogroupsof(usingKagan’s terms) “high-reactives” and “low-reactives.”Atfourmonths,the high-reactives criedand moved more inresponse to themovementof amobile than the low-reactives did; at fourteenand twenty-one months,those same high-reactives

stilltendedtodemonstratefearful reactions inresponse to novelsituations. Eighteen yearslater, McGrath’s teamtracked down the originalstudy subjects and lookedat the structure andreactivity of theiramygdalae. Sure enough,the babies identified ashigh-reactives at fourmonths had larger, more

hyperactive amygdalae atageeighteenthanthelow-reactives did—yet moreevidence that theamygdala’s response tonovelty is a strongpredictor oftemperamental anxietylevel. In a final wrinkle,McGrath’steam,usingnewgenetic coding techniques,discovered that highamygdala reactivityatage

eighteen was highlycorrelated with aparticular variation on aspecific gene known asRTN4. McGrath and hercolleagues hypothesizethat the RTN4 gene helpsdetermine howhyperreactive youramygdalawillbe,whichinturn helps determinewhether yourtemperamentwillbehigh-

reactive or low-reactive—which in turn helpsdetermine yourvulnerability to clinicalanxiety.This alphabet soup ofgenetic studies—hundredsif not thousands of whicharebeingconductedatanygiven time—can seeminanelyreductionist.Afewyears ago, I read a NewYork Times article about

studies attributing acorrelation betweencertain variants of twohuman genes—AVPR1aand SLC6A4—and a“talent for creative danceperformance.”‡ The goodnews, I suppose, is that ifthischangeshowwethinkaboutcharacterandfate,itmightalsochangehowwethink about courage andcowardice, shame and

disease,stigmaandmentalillness. If extreme anxietyis owed to geneticanomalies, should it beany more shameful thanmultiple sclerosisorcysticfibrosis or black hair, alldiseases or traits encodedbythegenes?Fiftyyearsago,wecould

plausibly blame thebehavior of our mothersforallmannerofneuroses

and unhappiness and badbehavior. Today, we canperhaps still blame ourmothers—but it may bemore plausible to blamethe genes they conferreduponusthanthebehaviorsthey displayed or theemotional wounds theyinflicted.

Forthatwhichisbutaflea-biting to one,

causeth insufferabletormenttoanother.—ROBERTBURTON,The

AnatomyofMelancholy(1621)

A number of privatecompanies will, inexchange for a drop ofyoursalivaandaheftyfee,sequence part of yourgenome in order to

provide information aboutyourrelativeriskfactorforvarious diseases. A fewyears ago, I paid a fewhundred dollars to acompany called 23andMe,and so I now know thatmy genes have left mewith, all things beingequal, a modestly higherthan average likelihood ofgetting gallstones, amodestly lower than

average likelihood ofdevelopingtype2diabetesor skin cancer, and aroughlyaveragelikelihoodof suffering a heart attackor developing prostatecancer. I also learned thatI am, according to mygenotype, a “fast caffeinemetabolizer,” that I am at“typical” risk for heroinaddiction and alcoholabuse,andthatIhavefast-

twitch sprinter’s muscles.(I also learned that Ihave“wet”earwax.)Iwashopingtofindout

which variants I have oftwoparticular genes, eachof which has at differenttimes been dubbed the“Woody Allen gene.” Thefirst gene, known asCOMT, is found onchromosome 22 andencodes the production of

an enzyme (catechol-O-methyltransferase) thatbreaks down dopamine intheprefrontalcortexofthebrain. The second gene,SLC6A4,alsoknownastheSERT gene, is found onchromosome 17 andencodesforhowefficientlyserotonin gets ferriedacrossthesynapsesofyourneurons.The COMT gene has

three variants.§ One(known as val/val)encodesforahighlevelofthe enzyme that breaksdown dopamine veryeffectively; the others(val/met and met/met)encode for lower levelsthat break down lessdopamine and leave moreof it in the synapses.Recent studies have foundthat people with the

met/met version tend tohave a harder timeregulating their emotionalarousal. The excess levelsof dopamine, researchersspeculate, are linked to“negative emotionality”and to an “inflexibleattentional focus” thatleaves people unable totearthemselvesawayfromobsessional preoccupationwith frightening stimuli—

traits that are, in turn,linked to depression,neuroticism, and,especially, anxiety. Peoplewith the met/met variantshow an inability to relaxafter exposure toapparently threateningstimuli, even when thosestimuli are revealed to benotdangerous after all. Incontrast, the val/valvariant was associated

with less intenseexperiencing of negativeemotions, a less reactivestartle reflex, and lessbehavioralinhibition.‖David Goldman, thechief of humanneurogenetics at theNational Institutes ofHealth, has labeledCOMTthe “worrier-warriorgene.” Those who possessthe val/val version,

accordingtoGoldman,are“warriors”: under stressfulconditions, this genevariant gives them abeneficial increase in theextracellularbrain levelofdopamine, whichpresumably makes themless anxious and lesssusceptible to pain andallows them to focusbetter.Theextradopaminealso gives them “better

working memory” whileunder stress. I wouldimagine that, forexample,the NFL quarterback TomBrady—who is legendaryfor his ability to makequick, smart decisionswhile under tremendouspressure(throwingtheballaccurately to the correctreceiverevenasthousandsofpoundsoflinebackerarebearing down on him at

highspeedandmillionsofpeople are watching andjudging him)—has thewarrior variant. But therearesituationsinwhichtheworrier version, which 25percent of the worldpopulation has, confersevolutionary advantages.Studies have shown thatcarriers of the met/metversion perform better oncognitive tasks requiring

memory and attentionwhen not under severestress; this suggests theworriers may be better atevaluating complexenvironments andtherefore at avoidingdanger. Each versionconfers a differentadaptive strategy: thosewith the worrier variantare good at stayingout ofdanger; those with the

warrior variant acteffectively once they’re indanger.aTheSERT gene also hasthreevariants:short/short,short/long, and long/long(these get abbreviated tos/s, s/l, and l/l). Startingin the mid-1990s, manystudies have found thatpeople with one or moreshort SERT allele (that is,those with the s/s or s/l

variant of the gene) tendto process serotonin lessefficiently than thosewithonlylongalleles—andthatwhen carriers of short-allele polymorphisms areshown fear-producingimages, they displaymoreamygdala activity thancarriers of the l/l pairing.Thiscorrelationbetweenaspecific gene and activityin the amygdala,

researchers hypothesize,helps account for thehigher rates of anxietydisorder and depressionthat other studies werefinding inpeoplewith thes/sversion.In the absence of life

stress, peoplewith the s/sand s/l genotypes weren’tany likelier to becomedepressed than peoplewith the l/l genotypes.

When stressful situationsarose, however—whetherin the form of financial,employment, health, orrelationship problems—those individuals withshort versions were morelikelytobecomedepressedor suicidal. Put the otherway around, those peoplewiththel/lvariantseemedpartly insulated againstdepression and anxiety

evenwhenunderstress.bKerry Ressler, a

psychiatrist at EmoryUniversity, has producedsimilar findings aboutother genes. Ressler hasdiscovered that whereassome genotypes seem toconfer increasedvulnerability to certainforms of anxiety disorder,other genotypes seem toconfer almost complete

resistance to them. Forinstance, a gene calledCRHR1 encodes thestructureofbrainreceptorsfor corticotropin-releasinghormone (CRH), which isreleased during activationof the fight-or-flightresponse or during timesof prolonged stress. Tooversimplify a little, thereare three variants of thisgene: C/C, C/T, and T/T

(the letters refer to thesequence of proteins thatencode the amino acidsthat make up your DNA).Lookingatagroupof fivehundred people frominner-cityAtlantawhohadsuffered high rates ofpoverty,trauma,andchildabuse, Ressler found thatthe variant of the CRHR1gene you inheritedstrongly predicted the

likelihood of yourdeveloping depression asan adult if you wereabused as a child. Onehomozygousversionofthegene (C/C)wasassociatedwith child abuse victimsbeingverylikelytodevelopclinical depression inadulthood; theheterozygous version ofthe gene (C/T) wasassociatedwithamoderate

likelihood of depression inadulthood; and, mostfascinatingly, the otherhomozygousversionofthegene (T/T) was notassociated at all withdepression in adulthood—the T/T version of thegene seems to confer onthese child abuse victimsalmostcompleteimmunityto depression. Child abuseseemed to have had no

long-term psychologicaleffect at all on those withthisversionofthegene.Ressler has also

discoveredsimilarfindingsin studies on the generesponsible for coding thefeedback sensitivity ofglucocorticoid receptors.Variations in this gene,known as FKBP5, seem tohave a powerful effect onthe susceptibility of

children to post-traumaticstress disorder. Whereasone variant of the FKBP5gene seems to beassociated with high ratesof PTSD, another variantseems to confer strongresistance: kids with theG/G variant developedPTSD at only around athird the rateofkidswithothervariants.Research like this

suggests that yoursusceptibility to nervousbreakdown is stronglydeterminedbyyourgenes.Certain genotypes makeyou especially vulnerableto psychologicalbreakdownwhensubjectedto stress or trauma; othergenotypes make younaturally resilient. Nosinglegene,orevensetofgenes,programsyoutobe

anxiousperse.Butcertaingene combinationsprogram you to haveeitherahighoralowlevelof hypothalamic-pituitary-adrenal activity: if youwerebornwithasensitiveautonomic nervous systemand then get exposed tostress in early childhood,your HPA system getssensitized even further, soit’s always hyperactive

later in life, producing anexcessively twitchyamygdala—which in turnprimes you to developdepression or anxietydisorders.If,however,youwere born with genesencoding low baselinelevelsofHPAactivity,youwill tend to have a highlevel of immunity to theeffects of even severestress.

Here,itseems,isatleasta partial explanation forwhat the Oxford scholarRobert Burton hadobserved back in 1621 inThe Anatomy ofMelancholy: “For thatwhich is but a flea-bitingto one, causethinsufferable torment toanother.”

Would finding out that IhavethewarriorversionoftheCOMTgenebeareliefbecause it would meanthat I am not, after all,genetically doomed tohigh levels of“neuroticism” and “harmavoidance”? Or woulddiscovering that I have,say, the long/long versionoftheSERTgenemakemefeel even worse than I

already do: to be blessedwith the genes foreasygoingness andresilienceandyettofeelsoanxious and neurotic—how pathetic would thatbe? I’d be learning that Ihad somehowmanaged tosquander a generousgeneticinheritance.In her 1937 book, TheNeurotic Personality of OurTime, Karen Horney, a

disciple of Freud, writesabout how a standardbehavioral tic of theneurotic is to reducehimself to nothing—I amsuch a loser, he says tohimself, look at all theobstacles that impede meand the handicaps thatconfine me; it’s a wonderthatIcanfunctionatall—inorder to relieve thepressure to accomplish

anything. The neuroticsecretly (sometimeswithout even knowing it)nurtures a powerfulambition to achieve as ameansofcompensatingforaweaksenseofself-worth.But the fear of failing toaccomplish, or of havinghis poor self-worthconfirmedbymanifestlackof achievement despite asincereefforttosucceed,is

too unbearable to abide.So as a psychological self-defensetactic,theneuroticplays up the infirmitiesthat ostensibly makeachieving successdifficult.Once these handicaps anddisadvantages areestablished,thepressureisoff: anything a neuroticaccomplishes merits extracredit.And if theneuroticfails? Well, that’s what

playing up all thesedeficits has aimed toprepare for: How couldyou expect anything butfailure given the barriersstackedagainsthim?ThustodiscoverthatIhavetheneurotic version of theCOMTgeneortheanxious-depressive SERT genemight at some level provetobe a relief.See, I couldsay, here’s proof that my

anxiety is “real.” It’s rightthere inmygenes.Howcananyoneexpectme—howcanI expect myself—to doanything much more thanmuddleanxiouslyalong?It’sa wonder I’ve been able toaccomplish anything givenmy disordered constellationofgenes!Nowletmehuddleunder the covers andwatchsoothingtelevisionshows.Late one night, the

report on my COMT genearrived.c I amheterozygous (val/met),whichmeans,basedonthelimited data so far, I amneither warrior norworrier but something inbetween.(A2005studyatSanDiegoStateUniversitydid find that people—mainly women—with theval/met variant tended tobe more introverted and

neurotic.)Sometimelater,I received theresults fromthegenotypingofmySERTgene: I’m short/short—meaning I’ve got thevariant that many studieshavefoundispredictiveofanxiety disorders anddepression when coupledwith life stress. If currentgenetic research is to bebelieved, I should—basedon my genotype—be

anxious and harmavoidant, inordinatelysusceptible to sufferingandpain.Shouldn’t this be

liberating? If beinganxious is geneticallyencoded, a medicaldisease, and not a failureof character or will, howcanIbeblamedorshamedorstigmatizedforit?Butcedingresponsibility

for your temperament andpersonality and baselinelevel of anxiety tohereditary bad luck—however well based ingeneticsciencethismaybe—quickly bleeds intovexing philosophicalterritory. The samebuilding blocks ofnucleotides, genes,neurons, andneurotransmitters that

make up my anxiety alsomake up the rest of mypersonality. To the extentthat genes encode myanxiety, they also encodemyself.DoIreallywanttoattribute the “me-ness” ofme to genetic factorscompletely beyond mycontrol?

The enigmatic phobiasof early childhood

deserve mention onceagain.… Certain ofthem—thefearofbeingalone, of the dark, ofstrangers—we canunderstandasreactionsto the danger of objectloss; with regard toothers—fear of smallanimals,thunderstorms, etc.—there is the possibilitythat they represent the

atrophied remnants ofan innate preparednessagainst reality dangersas is sowell developedinotheranimals.—SIGMUNDFREUD,TheProblemofAnxiety

(1926)

Howcouldsomethingasidiosyncratic as a specificphobiahavegottenpassed

frommymother tome tomy daughter? Can asimplephobiabegenetic?RecallthatFreud,latein

his career, observed thatcertaincommonphobias—fear of the dark, fear ofbeing alone, fear of smallanimals, fear ofthunderstorms—seem tohave evolutionarilyadaptive roots,representing “the

atrophied remnants of aninnate preparednessagainst reality dangerssuch as is so welldeveloped in otheranimals.” By this logic,certain phobias are socommon because theyarisefrominstinctivefearsthat have beenevolutionarilyselectedfor.In the 1970s, Martin

Seligman,apsychologistat

the University ofPennsylvania, elaboratedthis notion into what hecalled preparednesstheory:certainphobiasarecommonbecauseevolutionhas selected for brainsprimed to haveexaggeratedfearresponsesto dangerous things. Cro-Magnons who innatelyfeared—andwhothereforeavoided—falling off cliffs

or getting bitten bypoisonous snakes or bugsor being exposed topredators in open fieldswere more likely tosurvive.If the human brain ispredisposed to developfearsofcertainthings,thatcasts one of the mostfamousexperiments in thehistory of psychology in anew light. What if John

Watsonmisinterpreted theLittle Albert experimentthat Idiscussed inchapter2?What if the real reasonAlbert developed such aprofound phobia of rats,and so readily generalizedit toother furrycreatures,was not that behavioralconditioningissopowerfulbut that the human brainhas a naturalpredispositiontofearsmall

furry things? Rodents,after all, can carry lethaldiseases. Early humanswho acquired a prudentfear of rats would havehad an evolutionaryadvantagethatmadethemmore likely to survive. Soitmaybe that neither theoutward projections ofinner psychic conflict (asthe early Freud wouldhave it) nor the power of

behavioral conditioning(as Watson had it) is theprimary reason so manypeople today developrodent phobias; rather, itmay be the connection ofsuch fears to an atavisticresponse that is readilytriggered.For a long time,

primatologists believedmonkeys emerged fromthe womb with an innate

fear of snakes. Whenresearchers would observea monkey encounter asnake(orevenasnakelikeobject),themonkeywouldreact fearfully—seeminglya clear instance of purelyinnatepreparedness, of aninborn fear somehowhanded down through thegenes.ButSusanMineka,apsychologist atNorthwestern University,

discovered that monkeyswho have been separatedfrom their mothers andraised in captivity displayno fear when they firstencounter a snake. Onlyafter infantmonkeys haveobserved their mothersreacting fearfully to asnake—or after they havewatched a video ofanother monkey reactingfearfully to a snake—do

they later exhibit fearfulbehaviorwhen exposed toa snake themselves. Thissuggests young monkeyslearntobeafraidofsnakesfrom watching theirmothers—which in turnwould seem to be strongevidencethatthephobiaisacquiredbyenvironmentallearning rather thanthrough the genes. ButMinekadiscoveredanother

wrinkle: she found thatmonkeys could not easilyacquirefearsofthingsthatwere not intrinsicallydangerous. Youngmonkeyswhowereshownvideos of other monkeysreacting fearfully to asnake subsequentlydeveloped the fear ofsnakes—but monkeysshown (artfully spliced)videos of other monkeys

reacting fearfully toflowers or rabbits did notdevelopfearsofflowersorrabbits. Evidently, acombination of socialobservation and intrinsicdanger is necessary toproduce phobic-likebehaviorinmonkeys.Arne Öhman, the

Swedish psychologistwhose work on socialanxiety I mentioned in

chapter 4, points out thatwhile all humans areevolutionarily primed toacquire certain adaptivefears, most people do notdevelop phobias. This isevidence, Öhman argues,that there is geneticvariation in how sensitiveour brains are to eventhose stimuli we areevolutionarily primed tofear. Some people—like

my mother, my daughter,my son, and me—have agenetically encodedpropensitytoacquirefearsandtohavethembemoreintensethanaverage.dIn supportofSeligman’s

preparedness theory,Öhman found that thosephobias—includingacrophobia (fear ofheights), claustrophobia(enclosed spaces),

arachnophobia (spiders),murophobia(rodents),andophidiophobia (snakes)—thatwouldhavehadclearadaptive relevance in ourearly evolutionary historywere much harder toextinguish with exposuretherapy than phobias ofobjects like horses ortrains that were nothistorically“fearrelevant.”Furthermore, Öhman

foundthatevenphobiasofguns and knives—whichare clearly “fear relevant”today butwould not havebeen forNeanderthalsandother evolutionaryforebears—were mucheasier to extinguish thanfears of snakes and rats,suggesting that the fearswe are most readilyprimedfor,andleasteasilyrid of, were inscribed in

our genes relatively earlyinprimateevolution.Butwhat, ifanything, is

evolutionarilyusefulaboutemetophobia? Vomiting isadaptive; it can rid us oftoxins that could kill us.Whatwould account for agenotype for such aphobia?One speculative

possibility is thatemetophobiaisgenetically

derived from an impulsethat is evolutionarilyadaptive: avoiding otherpeople who are vomiting.Instinctivelyrunningawayfrom regurgitating peersmight have saved thoseearlyhominids frombeingexposed to ambient toxinsthat could have poisonedthem. Another possibilityis that an array ofgenetically conferred

temperamental traits andbehavioral and cognitivepredispositions, plus ahigh innate level ofphysiological reactivity,combined to enhance avulnerability to phobicanxiety—and maybeespecially, somehow, tothis particular phobicanxiety. My mother, mydaughter, and I all havehigh-reactive physiologies,

withjitteryamygdalaeandbodiesalwaysonDEFCON4 alert, which make usconstantly hypervigilantabout danger. My mother—like my daughter andlike me—is a high-octaneworrier;attimes,sheemitsa nervous thrum that ispractically audible. Ourphysiological reactivityand inhibitedtemperaments make all

threeofusmoregenerallynervous, and more likelyto experience intensenegative emotion whenexposed to a frighteningstimulus, than someonewith a low-reactive,uninhibitedtemperament.Here’s a conversation Ihadwithmydaughter thenight before a trip toFlorida not long after sheturnedsix.

“I’m afraid of the planeridetomorrow.”“There’s nothing to be

afraid of,” I say, trying toproject calm. “What is itabouttheplanethatmakesyouscared?”“The safety

instructions.”“The safety instructions?

What about the safetyinstructions?”“The part where they

talkaboutcrashing.”“Oh, planes are verysafe.Theplane’snotgoingtocrash.”“Thenwhydotheyhavetheinstructionstellingyouwhat to do if it doescrash?”“That’s just becausethere’s special rules thatsay flight attendants haveto give us the instructionsin order to keep us extra

safe. But flying is muchsafer than driving in acar.”“Then how come wedon’t have to listen tosafety instructions whenwegetinthecar?”“Susanna,” I yell downthe stairs, “can you cometalk to Maren aboutsomething?”Maren seems to havecomebyher fearof flying

without any overtinstruction from me. Shewas alreadytemperamentally equippedto worry about things, toscan the environment forpotential threats; thenaturalcastofhermind—like mine, like mymother’s, like those oftypical patients withgeneralized anxietydisorder—is such that she

seeks out and worries (inthe original sense of“playing with it,” turningit over in her mind toconsider it from everyangle) every worst-casescenario. Her dawningawareness of the safetyinstructions, with theirreferences to waterlandings and crashpositions, stimulated heranxiety.

Both my children sharemygift forcatastrophizing—for always imagining,and worrying about, theworst-case scenario, evenif that scenario is notstatistically likely. If Idetectasmallbumponmyface while shaving, Iimmediately worry that itisnot (as ismost likely)aburgeoning pimple butrather a malignant and

possibly fatal tumor. If Ifeelatwingeinmyside, Iinstantly worry that it isnota strainedmuscleoradigestive blip but ratherthe onset of acuteappendicitis or livercancer. If, while drivinginto the sunlight, I feel abit of dizziness, I amconvinced that it is not atrickoftheflickeringlightbutratheranearlysignof

astrokeorabraintumor.Some time later, we

wereonceagainpreparingto fly off for a familyvacation. Maren clutchedthe armrests on the planebefore takeoff, keenlyattentive to every clankand whir from theaircraft’s innards, askingaftereachone if thenoisemeant that the plane wasbroken.

“No,itdoesn’t,”mywifesaid.“But how do you

know?”“Maren, would we ever

put you somewhere thatwasdangerous?”Another noise from the

engine: Clank! “But whatabout that noise,” Marensays, tears in her eyes.“Does that noisemean theplaneisbroken?”

Sigh. The apple hasfallen all too close to thetree.e

Andthatwhichismoreto be wondered at,[melancholy] skips insome families thefather, and goes to theson, “or takes everyother, and sometimesevery third in a linealdescent, and doth not

always produce thesame, but some like,and a symbolizingdisease.”—ROBERTBURTON,The

AnatomyofMelancholy(1621)

The patient has beenshown to be aperfectionist, ambitiousto succeed though not

in an egocentric way,and sensitive to smalldegrees of failure.Whether suchpsychodynamicexplanations give thecauseof thedepressionis not known. Anxietyseems the largerfeature.—FROMCHESTER

HANFORD’S1948MCLEAN

HOSPITALREPORT

As unnerving as it hasbeen to watch mychildren’s anxiety developalonglinessimilartomine,it’s been equally so todiscover the similaritiesbetween my great-grandfather’sneurosesandmy own. If there is suchbehavioral similaritybetween my mother and

me, and between me andmykids,thenmightn’ttheanxious genotype run allthe way from my great-grandfather through mychildren—five generations(at least)ofthehereditarytaint?Chester Hanford diedthe summer I turnedsix. Imainly recall him as agentle, kindly presence,simultaneously

distinguishedanddecrepit,sittinginhiswheelchairinmy grandparents’ livingroom in suburban NewJersey, or in his room atthe nursing home nearby,wearing a burgundyblazer,adarktie,andgrayflannel slacks. After hisdeath in 1975, heremainedapresenceinourhouse, gazing out withwise, sad eyes from

various photos and livingon ina letter tohim fromPresident Kennedy thathung on the living roomwallalongsideapictureofthe two of themcampaigningtogetherwithJacquelineKennedy.WhenIwasgrowingup,

I knew only aboutChester’saccomplishments: his longandsuccessfuldeanshipat

Harvard; his respectedacademic publications onmunicipalgovernment;hisassociation with JFK overthe course of severaldecades, from Kennedy’sundergraduateyearstohistime in the White House.OnlywhenIgotolderdidIbegin to glean the darkbits: that he had sufferedfrom anxiety anddepression; that he had

undergone multiplecourses of electroshocktherapy; that he had beeninstitutionalized forextended periods manytimes between the late1940s and the mid-1960sand had been forced intopremature semiretirement(giving up his deanship)and then full retirement(leaving Harvard) as aresult; and that he had

spent some portion of hisfinaldecadesmoaninginafetal ball in the bedroomof his home in westernMassachusetts.What was the cause of

Chester’s afflictions? Wasthe problem primarilywhatwewould today callan anxiety disorder orclinical depression? Howclosely did his anxietiesresemblemine?

According to hispsychiatric records fromseveralhospitals,Chester’sgeneral existential fearsandanxietieswereakintomyown.Does thismeanIshare—whether owing tothetransmissionofspecificgenes or to a neuroticfamily culture establishedby our ancestors—aspecificpsychiatricdiseaseincommonwithmygreat-

grandfather? Or merelythat, in an inversion ofTolstoy, allpsychoneurotics areunhappyinthesameway?Readingaboutmygreat-

grandfather—especiallyafter having learned alittle bit about behavioralgenetics—has kindled asense of deep uneasiness,because so much abouthimremindsmeofmyself.

His nervousness. His fearsof public speaking. Histendency toprocrastinate.fHis obsessive handwashing.g His fixation onhis bowels.h His relentlessself-criticism. His lack ofself-esteem despite hisrespectablejob.Hisabilityto project a demeanor ofseeming imperturbabilityand good cheer whileroiling with internal

torment.i His emotionaland practical dependenceon his more outgoing,moretogetherwife.jHis first

institutionalization, at agefifty-six, seems to havebeen precipitated by theanxiety he felt about aseriesoflectureshewastogive to graduate students.“He had read a good dealthispastfall,”hisprincipal

psychiatrist wrote afterChester was admitted toMcLean Hospital in 1948,“butbegan to fear thathecould not organize thematerial into lectures.”Hefelt that other professorswere better than he wasand that he was notenough of a scholar toproduce satisfactorylectures. In the late springof 1947, Chester “became

very upset over hisinability to organize hiswork and be creative.Anxietyoverwhelmedhim.Hebecamequitedepressedandweptattimes.”Chester’spsychotherapists tried toget him to quiet hissuperego. “The patient’ssense of self-criticism hasbeen attacked as a factorin his depression, and

shows itself to be morerigid and excessive thanhis talents and virtueswarrant.” (Over the years,my own therapists havetried todo the same thing—only they generallydon’t call it a superegoanymore; they call it an“innercritic”ora“criticalself.”) In my great-grandfather’s case, thisdidn’t work. Despite

abundant evidence of hiseffectiveness as a scholarand an administrator, hecouldn’t subdue hisfeelings of ineffectualityandinferiority.(“Heisnotgladtothinkbackoverhisgreat usefulness to thecollege as in any wayameliorating his presentplight of uselessness,” hispsychiatrist wrote.) Theobjective evidence

suggests that he was afigure who commandedconsiderable respectamong both students andacademicpeers.Yetbythefall of 1947, hehad cometobelievehimselfa fraud,unequal to the task ofcomposing lectures ofsufficient interest andcogencyforhisstudents.How did this happen?

This was a man who had

manifestly thrived in hisprofessional and familylife.Hehadhad tenure atHarvard for decades, hadwritten a well-usedpolitical science textbook,and had been theacademic dean of thecollegeformanyyears.Hehad been married forthirty-two years. Heenjoyed an active sociallifeasamodestgrandeeof

the Cambridge scene andoften presided overmorning chapel servicesfor undergraduates. Afather, a grandfather, aHarvard professor anddean, a member in goodstandingofthecommunity—he had all the outwardtrappings of success,stability, and happiness.Yet inwardly he wascrumbling.

Today, my grandfathersays that until his fatherbrokedowncompletelyforthe first time in the late1940s, he had never seenany evidence that hisfather was anxious ordepressed. Yet, accordingto his medical records,Chester had always been“a rathernervousperson,”with a habit of—as hiswife, Ruth, had first

noticed when they werecourting—constantlyblinkinghiseyes.(Modernresearchers sometimes usea measurement they calleyeblink frequency as agauge of physiologicalanxiety.) Ruth alsorecalledtheanxietyhehadsuffered over a series oflectureshehadtogiveasayoung assistant professor,reporting to his doctors

thathehadbecome“quiteapprehensive andsleepless” for days inadvance.Combingthroughold correspondence, Icame across a letterChester had written toRuthwhilehewasajuniorprofessor at Harvardduring the First WorldWar, inwhichhedeclaredthathealmosthopedtobedrafted for combat—

becausedodgingbulletsonthe battlefield would beless nerve-racking thanhaving to give lectures toundergraduates.All of this suggests that

Chester had a nervousdisposition—what JeromeKagan would call abehaviorally inhibitedtemperament—that wasalmost certainly, to somedegree, hereditary. Both

his father and a maternalauntwerepronetovariousforms of anxiety anddepression. But thisnervous disposition, thisbehavioral inhibition, wasnot,forthefirstfiftyyearsof his life, undulydebilitating: asapprehensive andsusceptible to worry andinsomnia as he couldsometimes be, he

progressedsteadilyalongadignified professionalpath, gaining esteem andrespectashewent.Sowhy,aftermorethanfive decades of managinghisworryandmelancholy,didhe finally crack in thewinter of 1947, surprisingeven himself?k Accordingto the stress-diathesismodel of mental illness,clinical disorders like

anxiety and depressionofteneruptwhenageneticsusceptibility topsychiatric diseasecombines with lifestressors that overwhelmthe individual’s ability tocope. Certain people areblessed with genotypesprogrammed to withstandeven severe trauma; otherpeople, like my great-grandfather (and,

presumably, me), are lessnaturallyresilientandlosethe ability to cope whenthe stress of life becomestooheavy.My great-grandfather

was able to carry on hiswork until the SecondWorldWar.Butasvariouscolleagues were deployedto the war effort, histeaching load increased.“This put added strain on

him,” his principalpsychiatrist later reported,“and he became quitenervousandanxiousabouthisabilitytocontinue.”Hebecame chronically tired.After years of hosting asalon at his home inCambridge, he foundhimself too fatigued toentertain or even tosocialize at all; dealingwithpeoplewastoomuch

ofastrain.HesuggestedtoJames Conant, thepresident of Harvard, thathe might resign. (For themoment,Conantrequestedthathestayonasdean.)In the springof1945, a

close friend died. Alreadyfeeling worried and onedge,hebecameafter this(according to his wife)perpetually “jittery”—acondition that was

compounded as hesurveyed the casualty listsfrom thewar and saw thenames of many of hisformer students. Afteryears of teachingundergraduates, Chestersuddenly could no longerorganize his lectures. Onseveral occasions, hiswifehad to write the lecturesfor the freshman seminarhetaught.

At the urging of hisfamily physician, RogerLee,hetookamonthoffinthe summer of 1946. “Hefelt better after this,” hisrecords report, “and wasabletocontinuefairlywellthrough the next schoolyear.” But the followingspring, he again becameupset over his inability toorganize his work; heworried his lectures were

inferior. He also worriedobsessively about a trivialfinancial matter.Depression descended. Hewas able to carry out histeaching andadministrative dutiesduring the day, but atnight he was driven toweeping by tension andsadness. Dr. Lee advisedhim to cut back on hisworkload, and so, in the

fall of 1947, he retired asdean and returned to hisfull-time position in thegovernment department,teaching courses inpoliticalscience.At which point he

deteriorated rapidly. Bymid-October, he hadbecome “overtired,nervous, and upset abouthislecturesandfeltthathecould not carry on.” He

wouldstayupuntiltwointhe morning revising hislecturesandyetstillcouldnot sleep because he wasdissatisfiedwithhisdrafts,andsohewouldriseearlythenextdaytobeginworkagain. “He began to thinkhe was not any good anymore as a lecturer,” hisMcLean Hospital recordssay. “He began to thinkthat other professorswere

betterandthathewasnotup to his own standard.”The week before he wasfinally admitted to thehospital for the first time,hehadbecome“evenmoreapprehensive” about hislectures.Attimeshe“weptbitterly,” and he hadbeguntalkingofsuicide.In the “diagnosticimpressions” section ofChester’s intake file, the

hospital’s psychiatricdirector reports: “Thepatient gives theimpressionofhavingbeenan extremely valuableperson in his professionallife,aswellasverykindlyandhelpfulinhispersonalrelations. He wasoverconscientious andoverly self-critical, apersonofhighenergyandwork output, but a

procrastinator. He was aworrier, and has a historyof previous depression.Thus he has anxious andobsessional charactertraits. The change backfrom administrative toscholasticduties cutdownthe amount of satisfactoryactivity and of personalcontacts,andincreasedtheamount of contemplative,self-conscious and self-

critical thinking.Dependent and despairingattitudes increased. Hemight be diagnosed aspsychoneurosis, reactivedepression. The prognosisseems fairly good for aneasing of the presentsymptomsbutthefutureofhis adjustment isdoubtful.”If Chester Hanford’s

psychoneurotic ailments

and his genotype—and, toa lesser degree, his lifecircumstances—are similartomyown,doesthatmeana fate like his awaitsme?(“The future of hisadjustment is doubtful.”)Does my heredity doommetoasimilardownwardspiral if I am subjected totoo much stress? Whatmight already havebecomeofme if Ihadnot

hadrecourseto,atvarioustimes,thereadilyavailableantipsychotics, tricyclicand SSRI antidepressants,and benzodiazepines thatwere unavailable to mygreat-grandfather, whodeveloped his afflictionbefore the flowering ofmodernpsychopharmacology? Ifmy great-grandfather hadhad access to, say, Xanax

or Celexa, would he havebeen spared the multipleroundsofelectroshockandinsulin coma therapy, notto mention the monthsspent moaning in his bedinafetalball?Impossible to say, of

course. Whatever quotientof anxious and depressivegenes we may share,ChesterHanford and I aredifferent people, living in

different times underdifferent culturalconditions, with differentexperiences and differentstresses. Maybe Celexawouldn’t have worked onChester Hanford. (As wehave seen, the clinicalevidence on SSRIs ismixed.) And, who knows?Maybe I could havemuddled through withoutThorazine and imipramine

and Valium anddesipramine and Prozacand Zoloft and Paxil andXanax and Celexa andInderalandKlonopin.But somehow I don’t

think so. Which is whatmakes the similaritiesbetween us sodisconcerting—and whatmakes me wonder if thedifference betweenHoldingItTogether(asI’m

doing now and as ChesterHanford anxiously did forso many years beforefinallybreakingdown)andFailing to Do So is someingested chemicalcompounds that inwhatever mysterious andimperfect way interactwithmygenotype to keepme suspended, tenuously,overtheabyss.

My great-grandfather’sfirst stay at McLeanHospital was relativelyEdenic compared with hissubsequent ones.Over thecourse of sevenweeks, hehad daily psychotherapysessions, swam, playedbadmintonandcards,readbooks, and listened to theradio.Healsotookvariousmedications, whichprovide a representative

snapshot of thepharmacotherapy of thetime.lIn Chester’s dailypsychotherapysessions,hispsychiatrist tried to boosthis self-esteem and toreduce his anxiety bygettinghimtobelessrigidinhis thinking.Gradually,whether it was the talktherapy, the badminton,thedrugs,therespitefrom

work, or the passage oftime, his anxiety lifted.(For what it’s worth, hisprincipal psychiatrist gavegreatest credit to thetestosterone injectionsandthe regular physicalexercise.)Hewas releasedfrom thehospital onApril12, less depressed and nolonger actively suicidal.But in his dischargerecords, his psychiatrist

stated ominously thatwhile the symptoms ofanxiety had momentarilyabated, his worry-pronetemperament would likelytroublehimagain.A year later, he was

back,readmittedonMarch28, 1949, feeling, as thehospital director noted,“tense,anxious,depressed,and self-deprecatory” andsuffering from “insomnia

and an inability toconcentrate on his work.”The day before returningto McLean, he had toldRoger Lee, his familyphysician, that he wantedtokillhimselfbut“didnothave theguts for suicide.”Dr. Lee advised that headmithimselfagaintothehospital.Chester acclimated to

life in a psychiatric

hospital more quickly thistime, and within ten dayshe already seemed to thestaff to be more relaxed.But he was still talkingabout the same issues ason his previous admission—theanxiety,tension,andpractical difficulties hewas having in composinghis lectures and thegeneral inferiority he feltrelative to his faculty

peers.mAs the doctors

successfully “reassuredhim as to his ownconsiderable value in thecollege community,” hebecame within a fewweeks “a good deal moresociable and relaxed.” Hispsychiatrists believed thatthe combination of “relieffromtheresponsibilitiesofwork” and the positive

boost he got from theinjections of testosteroneallowed his confidence tobuild up fairly quickly,and he was able to leavethe hospital within amonth.n

My great-grandfather wasat least somewhatimproved for a time. Heresumed his full teaching

responsibilities at thecollegeandreturnedtohisscholarlywork.Forseveralyears,itseems,hefeltwelland worked productivelyandeffectively.Thenhefelltopieces.At a facultymeeting on

January 22, 1953, hiscolleagues noticed that heseemed “very tense,”“depressed,” and“disturbed.” That spring,

his depression becamesevere and his anxietyrose; he couldn’t work.Most alarmingly, as hiswifereported,hespenthisdays walking around thehouse “shrieking.” “Oh!Lord, lift up my soul,” hewould moan loudly.“Today, this is the end ofeverything, this is the endof everything. I shouldn’thave let myself go.”

Feeling“verystronglythathe was losing control ofhimself,” he sought anemergency consultationwith Dr. Lee, whorecommended that hereturn to the hospital. OnMay 5, 1953, he wasadmitted to McLean forthe third time in fiveyears.During his psychiatric

exam upon admission, he

was terribly anxious, andhis sense of shame abouthisanxietyanddepressionwas palpable.o By now hehad developed symptomsof what would today becalled obsessive-compulsive disorder: hewashed his handsconstantly, and he shavedand changed shirtsmultipletimesaday.Because testosterone

injections seemed to haverelieved his depressionduring his earlier stints atMcLean, the doctorsstarted him on a largedose. This time, however,“the sense of well-beingengendered by thetestosterone” could notovercome his symptoms.His psychiatrists judgedthattalktherapyanddrugswould be insufficient to

elevatehismood.Andso,onMay19,withhis ready acquiescence,Chester Hanfordunderwent his first roundof electroshock therapywith Kenneth Tillotson.pDuring each session,Chester would be sedatedand strapped tightly to abed. Orderlies wouldattach electrodes tovarious points on his skin

andslip inamouthguardsohewouldn’tbiteoffhisowntongue.Thenaswitchwould be flipped, andseveral hundred volts ofcurrent would passthrough his body, whichwouldtwitchandconvulseonthebed.After each session, he

wouldfeelalittleconfusedandhaveamildheadache—bothcommonsymptoms

ofelectroshock.Butwithina day of his first session,hetoldhisdoctorshewasfeelingconsiderablybetter.A few days later, he hadhis second round oftreatment. After that, thenursesonhiswardnoticedthat he seemed “morerelaxed, more pleasant,and more outgoing.” Hestopped ruminating abouthis problems. He seemed

markedly less anxious. Aweek later, after a thirdround of electroshock, thetransformation wasprofound: he “lookedwell,” was sleeping andeating, and was “laughinga great deal.” The nursesreportedhim tobe “muchless fearful than when hecame in,” no longer“running around askingthenurseswhetherhecan

do thisor that.”Hebeganspending a great deal oftimeinthegymwithotherpatients, playingbadminton and bowling—activities that he hadearlier implied to hispsychiatrist were beneaththe dignity of a sixty-two-year-old Harvardprofessor.Theelectroshocktherapy, it seemed, hadrestored (or injected) a

senseoffun.After a fourth round of

treatment, on June 2, hereported himself “relaxed”and eager to return towork. His wife, whovisitedhimfrequently,wasamazed:herhusbandwas,she told his psychiatrists,“more the way he wasmany years ago.” Chesterhimself told the staff thathefelt“morelikehimself.”

To me this soundsuncannily like what PeterKramer reported inListeningtoProzac:thatthepatients he put on Prozacin the1990shadtoldhimthemedicationmadethemfeel “more likethemselves.”Westillhaveremarkably

littleunderstandingofhowelectroshock therapyworks. Metaphorically,

electroshock seems tofunction the way hittingCtrl+Alt+Delete on yourcomputer does; it rebootsthe system, restoring thesettings on the neuraloperating system. Theoutcome statistics arecompelling. Though thepracticewentoutofvoguein the 1970s and 1980s—in part because JackNicholson’sportrayalofan

electroshockpatient inthemovie version of KenKesey’s novel One Flewover the Cuckoo’s Nestconvinced people thetechnique was barbaric—modern studies show thatthe recovery rates fromsevere depression may behigher with electroshockthanwithanykindofdrugor talk therapy. Theexperience of my great-

grandfather,atleastintheshort term,wouldseemtobearthatout.Couldtherebeanymore

compelling evidence thatanxietyanddepressionareirreducibly “embodied” or“enmattered,” in thefashion observed sinceAristotle?Byhis third triptothepsychiatrichospital,Chester Hanford’spsychiatrists seem largely

to have given up ontalkingorpsychoanalyzinghim out of his depressionand anxiety; hispersonality and characterseemedsofixedastoresist“adjustment.” But zappinghis brain with a fewhundred volts ofelectricity, on the otherhand—rewiring theconnections—seemed todothetrickjustfine.After

four electroshocktreatments, the hospitaldirectorwrotethatChester“showed tremendousimprovement.”On June 9, 1953, aboutamonthafterenteringthehospital,acheerfulChesterwas discharged into thecare of his wife. Theypromptly left for vacationin Maine, where for thefirst time in years he

eagerly anticipated thearrivalof the fall semesterandanewcropofstudentstoteach.

I wish Chester Hanford’sstory ended on thishopeful note. But in timehis anxiety returned, andhewascompelledtoretire.Throughoutthe1950sand1960s, he went regularly

to McLean—and, later, tothe New EnglandDeaconess Hospital indowntown Boston—formoreelectroshocktherapy.At one point, a too-potentdrug cocktail nearly killedhim. For a period in thelate 1950s, his anxietiesand compulsions got sobad that his doctorsconsidered performing aprefrontal leucotomy—a

partial lobotomy.(Ultimately, he wasspared.)For the balance of his

lifetime,hekindoflimpedalong. He would be okayforstretches—andthenforstretches he wouldn’t be.Evenwhenhewasn’tokay,he could pull himselftogether for appearance’ssake. Mymother recalls asummer day in the mid-

1960s when a party wasplanned at the Hanfordhome in westernMassachusetts. Family andfriends from all over NewEngland were to begathering that evening.Throughoutthedayoftheparty, a haunted moaningemanated from Chester’sbedroom; my mothercringed to think what hisappearance at the party

wouldbelike—ifhecouldmanage an appearance atall.Yetastwilightfellandthe party began, heemerged downstairs as agracious, even sociablehost. And then the nextday he retreated again tohis room, to his fetal curlandhismoaning.My parents recall

Chester seeming lessanxious and agitated

during his years in thenursing home—a fact thatmyfathersuspectsmaybeexplained by the generousdoses of Valiumadministered there.Benzodiazepines may,finally, have successfullytranquilized his anxietyinto submission. Orperhaps being liberatedfrom the stresses of workrelaxedhim.

In immersing myself sodeeply in thepsychopathologies of mygreat-grandfather, and inidentifying rather stronglywith them, I—ashypochondriacal andprone to worry as I am—have naturally grownconcerned that thehereditary taint will soonreduce me, too, topermanent weeping and

shakinginmyroom.WhenItellDr.W.about

this, he says, “As youknow,Idon’tplacealotofstock in geneticdeterminism.”Icitesomeoftherecent

studies suggesting apowerful heritablecomponent to anxietydisordersanddepression.“Okay, but you’re three

generations removed from

your great-grandfather,”hesays.“Youshareonlyafractionofhisgenes.”Trueenough.Andinany

case, genes andenvironment interact incomplex ways. “[Agenetically] inheritedreaction to potentialdangermaybeaboonorabane,” says DanielWeinberger, the leadresearcher on one of the

firstSERTgenestudies.“Itcanplaceusat risk forananxiety disorder, or inanother situation it mayprovide an adaptivepositive attribute such asincreased vigilance. Wehave to remember thatanxiety is a complicatedmultidimensionalcharacteristic of humanexperience and cannot bepredictedbyanyformofa

singlegene.”Dr.W. and I talk aboutthe way academicconferences on anxietyhave been placingincreasing emphasis onhow the psychologicaltraits of resilience andacceptance can be crucialbulwarks against bothanxiety and depression;much of the cutting-edgeresearch and treatment

focusesinparticularontheimportance of cultivatingresilience.“Yes!”Dr.W. says. “We

need to work on makingyoumoreresilient.”When I tell him what

I’ve learned about theserotonintransportergene,and about how peoplewithcertaingenotypesarefar more likely to liveanxious, unhappy, and

unresilient lives, Dr. W.remindsme howmuch hedislikes the modernemphasis on the geneticsand neurobiology ofmental illness because ithardensthenotionthatthemind is a fixed andimmutablestructure,whenin fact it can changethroughoutalifetime.“Iknow,”Isay.I’veread

about the recent findings

on neuroplasticity—aboutthe way the human braincan keep forming newneuronal connections intoold age. I tell him that Iunderstandtheimportanceof resilience in combatinganxiety.Buthow,Iask,doIgainthatquality?“You’re already more

resilient than you know,”hesaid.

* In 2011, Giovanni Salum, aBrazilian psychiatrist, releasedthe results of one of the largest-scalestudiesoftheheritabilityofanxietydisorderseverconducted.Surveying data on ten thousandpeople, Salum found that a childwho has no relatives with ananxiety disorder has only a one-in-ten chance of developing onehimself. If that same child hasone relative with an anxiety

disorderinhisfamily,hisoddsofdeveloping an anxiety disorderrisetothreeinten.Andifalargemajority of members have ananxietydisorder, thechild’soddsrisetoeightinten.

† This squares with what studieshave found about the relativelyfixed percentage of soldiers whoare especially prone to breakdown when exposed to combatstress.

‡ To be sure, genetic researchers

grant that anxious emotion, or atalent for dancing, must havemultiple genetic (andenvironmental) causes. But thetrend toward reducing emotionsto their underlyingneurochemical correlates, and tothe genes that underwrote them,canseeminexorable.

§ Let me stipulate here that I amnotageneticscientist,andthatIam oversimplifying a vast andcomplexbodyofresearch.Foran

easy-to-understand book aboutpsychiatricgeneticsbyanexpert,I recommend The Other Side ofNormal: How Biology Is Providingthe Clues to Unlock the Secrets ofNormalandAbnormalBehaviorbyJordanSmoller.

‖Many studieshave supported theconnectionbetween themet/metvariant of the COMT gene andunusuallyhighlevelsofanxiety—though, interestingly, mainly inwomen.Onestudy,conductedby

investigators at the NationalInstitute on Alcohol Abuse andAlcoholism, looked at twodisparate groups of women—Caucasians from suburbanMarylandandPlainsIndiansfromrural Oklahoma—and found thatin both populationswomenwiththe met/met variant reportedmuch higher levels of anxietythan did women with the othervariants. (The met/met variantalso correlated with having only

aquartertoathirdofthetypicalquantity of the catechol-O-methyltranferase enzyme in thebrain.) When women with themet/met variant were placed inanEEGmachine,theyexhibiteda“low-voltage alpha brain-wavepattern,”whichhasbeenfoundtobe associated with both anxietydisorders and alcoholism. Inshort, the study revealed aconnection not only between thegene and enzyme levels, and

betweenenzymelevelsandbrainactivity, but also between brainactivity and subjectivelyexperienced levels of anxiety.Another study, conductedamongboth German and Americanpopulations in 2009, found thatpeoplewith themet/metversionofthegeneexhibitedhigher-than-average physiological startleresponseswhenshownaseriesofunpleasant pictures and were,accordingtostandardpersonality

tests,higheringeneralanxiety.

a These different evolutionarystrategies seem to apply even infish. Lee Dugatkin is a professorof biology at the University ofLouisville who studies guppybehavior.Someguppiesarebold;some are timid. Bold maleguppies, Dugatkin observes, aremore likely than timid maleguppiestoattractfemalestomatewith. But the bold guppies, intheir brazenness, are also more

likelytoswimnearpredatorsandgeteaten.Thetimidguppiesthustendtolivelonger—andthereforetoprolongthetimeduringwhichthey have opportunities tomate.Both types of guppies, the boldand the timid, represent aviableevolutionary strategy: Be boldandmatemorebutbemorelikelyto die young—or be timid,mateless, and be more likely to livelonger.There’sanadaptivevalueto being a bold guppy—but

there’s also an adaptive value tobeingatimidone.It’snothardtosee the same evolutionarystrategies atwork among humanpopulations. Some people liveboldly,matepromiscuously, takerisks, and tend to die young(think of the bold and tragicKennedy clan); others livetimidly,mateless,areriskaverse,and tend to be less likely to dieprematurelyinaccidents.

bNoteverystudyhasborneoutthe

initial hypothesis that having ashort version of the SERT allelemakes you more susceptible toanxiety or depression. Forinstance, while epidemiologicalstudiesconsistentlyfindthatratesofclinicalanxietyanddepressionare lower in Asia than in Europeand North America, genetictesting has found that theprevalenceof thes/sSERT alleleis markedly higher among EastAsian populations than among

Western ones—which raisesintriguing questions about howculture and social structureinteract with genetics to affecttheratesandintensityofanxietyamong individuals in differentsocieties.

c I asked my brother-in-law, amedical student and formerbiochemistry major, to take theraw genomic data that 23andMeprovided and plug it into open-source genome databases to

figureoutwhatvariant Ihaveofthe COMT gene. And though23andMe does not currentlyprovideclientswitheventherawdataonSERTvariants,Iprevailedupon some neuroscientist friendsofmine to testme for it, on thecondition that I not reveal theirnames since they receive federalgrant funding and are notsupposed to perform the test onanyonewho isnotofficiallypartofastudy.

d Interestingly, different phobiasseem to trigger different parts ofour neurocircuitry and to havedifferent genetic roots. This istrue to my own experience. Asphobic as I am of flying and ofheights and of vomiting and ofcheese, Ihaveno inordinate fearofsnakesorratsorotheranimals;in fact, theanimalkingdommaybeoneofthefewareaswhereI’mactually less fearful than I oughttobe.Ihavebeenbadlybittenby

adog(whichresultedinatriptothe emergency roomwhen Iwaseight), by a snake (I once had apet bull snake named Kim), andwas once viciously attacked by,of all things, a kangaroo, whichI’d mistakenly thought wanted ahug. (Long story.) I’d be muchhappier covered in a pile of(nonpoisonous) snakes and ratsthan flying through even themildestturbulence.

e I should say here that perhaps

because both my children havereceived early psychotherapy fortheir anxiety—to help them takecontrol of what we call their“worry brains”—they both seemtobelessanxiousthantheywerea few years ago. Maren is stillemetophobic,butshe’sdevelopedtechniquesformanagingherfear,and she’s less anxious—and infactquiteself-confident—inmostareas of her life. Nathanielremains an imaginative

catastrophizer,buthis separationanxiety has become a little lesssevere. Temperamentally, theywill probably remain prone toanxietyfortheirentirelives—butmyhopeisthattheywillbeableto manage their fear, and evenharness it inproductiveways, insuch a fashion that they will beabletothrivedespiteit.

f From a 1948 “diagnosticimpressions” report: “He wasoverconscientiousandoverlyself-

critical, a person of high energyand work output, but aprocrastinator.”

g From a report by his principalpsychiatristduringhis sojournatMcLean in May 1953: “It hasbeennoted thathe isdevelopingan increasing hand-washingritual.Thishasnotbeentakenupinpsychotherapy sessions since Ifeel it is important not to givehim the impression that we areunduly critical of his personal

activities.”

h From a handwritten physician’snote from the spring of 1948:“Thepatienthashadan irritablelarge bowel … for years.” Fromanother note some years later:“Patient chronically worriedabouthisbowels.”

i“Patientisverypleasant,”anursenoted, observing Chester as heambled around the ward duringhis second stint at McLean.“Gives the impression that

nothingcouldupsethim.”

j “Hehasalsobeenquiteaburdenon his wife.” That’s from apsychiatrist’s notes duringChester’sthirdstayatMcLean.

k “Mr. Hanford remarked that hehad once visited one of hisstudentsinthe[neuropsychiatric]ward at the Mass General andwasquiteimpressedwiththewaythe doors, etc., were keptlocked,” his psychiatrist noted.“Hesaid, ‘IneverexpectedthatI

wouldfindmyselfunderthesamecircumstances;IalwaysfeltthatIcouldtakecareofmyself.’”

l He took methyltestosterone, ananabolic steroid given to himbyinjection, which at midcenturywas considered a standardtreatment for depression inmen;Oreton, a synthetic testosteronethattodayseemstobeprescribedonly to boys suffering delayedpuberty;chloralhydrate,theold-fashioned nineteenth-century

ethanol-chlorine derivative thatremained popular as a sedativeand sleepaiduntil thearrival ofbenzodiazepines; and Donatal, apotent combination ofphenobarbital (the barbiturate inLuminal) and hyoscyamine andatropine (which are both plantderivatives from the deadlynightshade family), which wasprescribedforhisagitatedbowelsandnerves.

m As his principal psychiatrist

writes, “In talking with him Ihavelaidagooddealofstressonhis previous value as anindividual in his work for thecollege. I have led him to takemoresatisfactioninhisexecutiveand teaching accomplishments.Thus it has been possible tosomewhat relax his self-criticalattitude.”

n On April 29, 1949, Chester wasreturned to the care of his wifeand his personal physician, Dr.

Lee, his file noting, “There aresome evidences of tension anddepressionstillpresent,butithasbeen possible for him to bedischargedhomeasimproved.”

o “His colleagues recently havegiven him support during hisillness these past five years, andactually he is not carrying theworkload he should, and heknowsit,”onepsychiatristnoted.“Hehasalsobeenquiteaburdenon his wife who has found it

necessary to prepare some of hislecturesforhim.”

p During this same period, Dr.Tillotson also administeredelectroshock treatment to thepoet Sylvia Plath, who recordedthe experience in her novel, TheBellJar.

CHAPTER10

AgesofAnxiety

The philosophic studyof the several branchesof sociology, politics,charities, history,education, shall never

beeveninthedirectionofscientificprecisionorcompleteness until itshall have absorbedsome, at least, of thesuggestions of thisproblem of Americannervousness.—GEORGEMILLERBEARD,AmericanNervousness

(1881)

In April 1869, a youngdoctorinNewYorknamedGeorge Miller Beard,writing in the BostonMedical and SurgicalJournal, coined a term forwhat he believed to be anew and distinctivelyAmericanaffliction,onehehad seen in thirty of hispatients: “neurasthenia”(from neuro for “nerve”and asthenia for

“weakness”). Referring toit sometimes as “nervousexhaustion,” Beard arguedthat neurasthenia afflictedprimarily ambitious,upwardlymobilemembersof the urban middle andupper classes—especially“the brain-workers inalmost everyhouseholdofthe Northern and EasternStates”—whose nervoussystemswereovertaxedby

a rapidly modernizingAmerican civilization.Beard believed that hehimself had suffered fromneurasthenia but hadovercome it in his earlytwenties.Born in a small

Connecticut village in1839,Beardwasthesonofa Congregational ministerand the grandson of aphysician. After attending

prep school at PhillipsAcademy in Andover,Massachusetts,hewentontoYale,wherehebegantosuffer from the array ofnervous symptoms thatwould afflict him for thenext six years and that hewould later observe in hispatients: ringing in theears, pains in the side,dyspepsia, nervousness,morbid fears, and “lackof

vitality.” By his ownaccount, Beard’s anxioussuffering was promptedlargely by his uncertaintyabout what career topursue—though there isalso evidence that heanguishedoverhis lackofreligious commitment.(Two of Beard’s olderbrothers had followed hisfatherintotheministry;inhis diary, he chastises

himselfforhisindifferenceto spiritual concerns.)Once he decided tobecome a physician,however, his doubts lefthim and his anxietydissipated. He enteredmedical school at Yale in1862, determined to helpothers plagued by theanxious suffering that hadonceafflictedhim.Influenced by Darwin’s

recent work on naturalselection, Beard came tobelieve that cultural andtechnological evolutionhad outstripped biologicalevolution, puttingenormous stress on thehuman animal—particularly those in thebusiness and professionalclasses, who were mostdriven by statuscompetition and the

burgeoning pressures ofcapitalism. Even astechnological developmentandeconomicgrowthwereimproving material well-being, the pressure ofmarket competition—alongwiththeuncertaintythat took hold as thefamiliar verities fell awayunder the assault ofmodernity andindustrialization—

produced great emotionalstress, draining Americanworkers’ stock of “nerveforce”andleadingtoacuteanxiety and nervousprostration. “In the oldercountries, men plod alongin the footsteps of theirfathers, generation aftergeneration, with littlepossibility and thereforelittlethoughtofenteringahigher social grade,”

Beard’s colleague A. D.RockwellwroteintheNewYork Medical Journal in1893. “Here, on thecontrary,nooneiscontenttorestwith thepossibilityever before him ofstepping higher, and theraceoflifeisallhasteandunrest. It is thus readilyseen that the primarycause of neurasthenia inthis country is civilization

itself, with all that termimplies, with its railway,telegraph, telephone, andperiodical pressintensifying in tenthousand ways cerebralactivityandworry.”*Beard believed thatconstantchange,combinedwiththerelentlessstrivingfor achievement, money,and status thatcharacterized American

life, produced rampantnervous weakness.†“American nervousness isthe product of Americancivilization,”hewrote.TheUnitedStateshadinventednervousness as a culturalcondition: “The Greekswere certainly civilized,buttheywerenotnervous,andintheGreeklanguagethere is no word for thatterm.”‡ Ancient cultures

could not haveexperienced nervousness,he argued, because theydidn’t have steam power,the periodical press, thetelegraph, the sciences,and themental activity ofwomen: “Whencivilization,plusthesefivefactors, invades anynation, it must carrynervousness and nervousdisease along with it.”

Beard also argued thatneurasthenia affected onlythemore“advanced”races—especially the Anglo-Saxon—and religiouspersuasions; he observedthat “no Catholic countryis very nervous.” (On itsface, this is a dubiousproposition,andBeardhadno real evidence tobuttress it. On the otherhand, rates of anxiety in

modern Mexico, aprimarilyCatholiccountry,aremuchlowerthanintheUnited States. A 2002WorldHealthOrganizationstudy found thatAmericans are four timesmore likely to suffer fromgeneralized anxietydisorder than Mexicans—and some research hasfound that Mexicansrecover from anxiety

attackstwiceasquicklyasAmericans. Interestingly,when Mexicans immigrateto theUnited States, theirrates of anxiety anddepressionsoar.)Neurastheniawasaself-

flattering diagnosis, sinceit was thought to affectprimarily the mostcompetitivecapitalistsandthose with the mostrefinedsensibilities. Itwas

a disease of the elites; inBeard’s estimation, 10percentofhisownpatientloadwasmadeupofotherphysicians, and by 1900“nervousness” haddefinitively become amark of distinction—asignifierofbothhighclassandculturalrefinement.§Beard’s books contain

case studies and elaboratesymptomatologies that

sound strikinglycontemporary to themodern ear. InAPracticalTreatise on NervousExhaustion, published in1880, he expatiates forhundreds of pages on thesymptoms of nervousexhaustion. “I begin withthe head and brain,” hewrites, “and godownwards.” The listincludes tenderness of the

scalp; dilated pupils;headache; “MuscoeVolitantes, or floatingspecks before the eyes”;dizziness; ringing in theears; softness of voice (avoice “wanting inclearness and courage oftone”); irritability;numbness and pain in theback of the head;indigestion; nausea;vomiting; diarrhea;

flatulence(“withannoyingrumbling in the bowelsthese patients complain ofveryfrequently”); frequentblushing(“Ihaveseenverystrong,vigorousmen,whohavelargemuscularpowerand great capacity forphysical labor,who,whilein a neurasthenic state,would blush like younggirls”); insomnia;tendernessoftheteethand

gums;alcoholismanddrugaddiction; abnormaldryness of the skin;sweatingof thehandsandfeet (“Ayoungmanundermy care is so distressed[by his sweating] that hethreatenssuicideunlessheis permanently cured”);excess salivation (or,alternatively, dry mouth);back pain; “heaviness oftheloinsandlimbs”;heart

palpitations; musclespasms; dysphagia(difficulty swallowing);cramps; tendency to gethay fever; sensitivity tochanges in the weather;“profound exhaustion”;ticklishness; itching; hotflashes; cold chills; coldhandsand feet; temporaryparalysis; and gaping andyawning.Ontheonehand,this panoply of symptoms

is so broad as to bemeaningless; these are thesymptoms,moreorless,ofbeing alive. On the otherhand, this litany resonateswith the twenty-first-century neurotic’s—itsounds, in fact, not unlikemy weekly catalog ofhypochondriacalcomplaint.Neurasthenia alsoencompassed what we

would today call phobia.Beard’s case studies rangefrom the lightning phobic(“One ofmy patients tellsmesheisalwayswatchingthe clouds in summer,fearing that a storm maycome. She knows this isabsurd and ridiculous, butshe declares she cannothelp it. In this case thesymptom was inheritedfrom her grandmother;

andeven inher cradle, asshe is informed by hermother,shesufferedinthesame way”) to theagoraphobic (“One of mycases, a gentleman ofmiddle life,couldwalkupBroadway withoutdifficulty, because shopsandstores,hesaid,offeredhim an opportunity ofretreat,incaseofperil.Hecould not, however, walk

up Fifth Avenue, wheretherearenostores,nor inside streets, unless theywere very short.He couldnot pay a visit to thecountry in any direction,butwashopelesslyshutupin the city during the hotweather. One time, inriding in the stage upBroadway,onturningontoMadison Square, heshriekedwithterror,tothe

astonishment of thepassengers. The man whopossessed this interestingsymptom was tall,vigorous, full-faced, andmentally capable ofendurance”); from theclaustrophobic (who fearenclosed spaces) to themonophobic (who fearbeing alone; “One manwas so afraid to leave thehousealonehepaidaman

$20,000tobehisconstantcompanion”); from themysophobic (who fearscontamination and mustwash her hands twohundred times a day) tothepanophobic(whofearseverything). One ofBeard’s patients had amorbid fear of drunkenmen.By the turn of the

century, the language and

imagery of neurastheniahad permeated deep intoAmerican culture. If youyourself didn’t suffer fromit,yousurelyknewpeoplewho did. Political rhetoricand religious sermonsaddressed it; consumeradvertisements offeredremedies for it.Magazinesand newspapers publishedarticlesabout it.TheodoreDreiser and Henry James

populated their novelswith neurastheniccharacters. The languageof neurasthenic distress(“depression,” “panic”)crept into economicdiscourse. Nervousness, itseemed, had become thedefault psychological stateand cultural condition ofmodern times. Disruptedby the transformations ofthe Industrial Revolution

and riven by Gilded Agewealth inequality, theUnitedStateswasrifewithlevels of anxietyunmatched in humanhistory.OrsoBeardclaimed.But

wasitreally?According to the latest

figures from the NationalInstituteofMentalHealth,some forty millionAmericans, or about 18

percent of the population,currently suffer from aclinical anxiety disorder.RecenteditionsofStress inAmerica,areportproducedeachyearbytheAmericanPsychological Association,have found a badly“overstressed nation” inwhich a majority ofAmericans describethemselves as“moderately” or “highly”

stressed, with significantpercentages of themreporting stress-relatedphysicalsymptomssuchasfatigue,headache,stomachtroubles, muscle tension,and teeth grinding.Between 2002 and 2006,the number of Americansseeking medical treatmentforanxiety increased from13.4 million to 16.2million. More Americans

seekmedicaltreatmentforanxietythanforbackpainormigraineheadaches.Surveys by the AnxietyandDepressionAssociationofAmericafindthatnearlyhalf of all Americansreport “persistent orexcessive anxiety” in theirdaily work lives. (Othersurveysfindthatthreeoutof four Americans believethere is more workplace

stress today than in thepast.)Astudypublishedinthe American Psychologistfound that 40 percentmore people said they’dfelt an impending nervousbreakdown in 1996 thanhadsaidsoin1957.Twiceas many people reportedexperiencing symptoms ofpanicattacksin1995asin1980.‖ According to anational survey of

incoming freshmen, theanxiety levels of collegestudents are higher todaythan at any time in thetwenty-five-year history ofthe survey. When JeanTwenge, a professor ofpsychology at San DiegoStateUniversity, lookedatsurvey data from fiftythousand children andcollege students betweenthe 1950s and the 1990s,

shefoundthattheaveragecollege student in the1990s was more anxiousthan 85 percent ofstudents in the 1950s andthat “ ‘normal’schoolchildren in the1980s reported higherlevelsofanxietythanchildpsychiatric patients in the1950s.” (Robert Leahy, apsychologist at WeillCornell Medical College,

characterized this findingcolorfully in PsychologyToday: “The average highschool kid today has thesame level of anxiety asthe average psychiatricpatientinthe1950s.”)Thebaby boomers were moreanxiousthantheirparents;Generation X was moreanxious than theboomers;themillennialsareturningout to be more anxious

thanGenerationX.Ratesofanxietyseemtobe increasing all aroundtheworld.AWorldHealthOrganization survey ofeighteen countriesconcluded that anxietydisordersarenowthemostcommonmental illness onearth, once againovertaking depression.StatisticsfromtheNationalHealth Service reveal that

British hospitals treatedfourtimesasmanypeoplefor anxiety disorders in2011 as they did in 2007while issuing recordnumbers of tranquilizerprescriptions. A reportpublished by Britain’sMental Health Foundationin 2009 concluded that a“culture of fear”—markedby a shaky economy andhyperbolic threat-

mongering by politiciansand the media—hadproduced “record levels ofanxiety”inGreatBritain.Given the “record levels

ofanxiety”weseemtobeseeing around the world,surely we must today beliving in themost anxiousage ever—more anxiouseven than George Beard’seraofneurasthenia.How can this be?

Economic disruption andrecent global recessionnotwithstanding, we liveinanageofunprecedentedmaterial affluence.Standards of living in theindustrializedWestare,onaverage, higher than ever;life expectancies in thedeveloped world are, forthe most part, long andgrowing.Wearemuchlesslikelytodieanearlydeath

than our ancestors were,much less likely to besubjectedtothehorrorsofsmallpox, scurvy,pellagra,polio,tuberculosis,rickets,and packs of rovingwolves,nottomentionthechallenges of life withoutantibiotics, electricity, orindoorplumbing.Lifeis,inmany ways, easier than itused to be. Thereforeshouldn’t we be less

anxious than we oncewere?Perhaps in some sense

the price—and surely, inpart, the source—ofprogress andimprovements in materialprosperity has been anincrease in the averageallotment of anxiety.Urbanization,industrialization, thegrowth of the market

economy, increases ingeographic and classmobility, the expansion ofdemocratic values andfreedoms—all of thesetrends, on their own andin concert, havecontributed to vastlyimproved material qualityof life for millions ofpeople over the lastseveralhundredyears.Buteach of these may also

have contributed to risinganxiety.Until the Renaissance,there was scarcely anyconceptofsocial,political,technological,oranyotherkindof progress.This lenta kind of resignation tomedieval emotional lifethat may have beenadaptive: the sense thatthingswouldalwaysbeasthey were was depressing

butalsocomforting—therewasnohavingtoadapt totechnological or socialchange; there were nohopes for a better life indanger of being dashed.While life was dominatedby the fear—andexpectation—of eternaldamnation(oneFranciscanpreacher in Germany putthe odds in favor ofdamnation for any given

soul at a hundredthousand to one),medieval minds were notconsumed, as ours are,with the hope ofadvancement and the fearofdecline.Today, especially inWestern capitalistdemocracies, we alsoprobablyhavemorechoicethan ever in history: wearefreetochoosewhereto

live, whom to court ormarry, what line of workto pursue, what personalstyle toadapt.“Themajorproblem for Americans isthat of choice,” the latesociologist Philip Slaterwrotein1970.“Americansare forced into makingmorechoicesperday,withfewer ‘givens,’ moreambiguous criteria, lessenvironmental stability,

and less social structuralsupport, than any peoplein history.” Freedom ofchoice generates greatanxiety.BarrySchwartz, apsychologist atSwarthmore College, callsthis “the paradox ofchoice”—the idea that asthe freedom to chooseincreases,sodoesanxiety.Maybe anxiety is, insome sense, a luxury—an

emotion we can afford toindulge only when we’renot preoccupied by “real”fear. (Recall that WilliamJames made a version ofthis argument in the1880s.) Perhaps preciselybecause medievalEuropeans had so manygenuine threats to beafraidof (theBlackDeath,Muslim invaders, famine,dynastic turmoil, constant

military conflict, anddeath, always death,imminently present—theaverage life expectancyduring the Middle Ageswas thirty-five years, andone out of every threebabies died beforereaching the age of five),they were left with littlespace to be anxious, atleast in the sense thatFreud, forexample,meant

neurotic anxiety—anxietygenerated from withinourselves about things wedon’t really have rationalcause to be afraid of.Perhaps the Middle Ageswere relatively free ofneurotic anxiety becausesuch anxietywas a luxuryno one could afford intheir brief, difficult lives.In support of thispropositionarethesurveys

showing that people indeveloping nations havelower rates of clinicalanxiety than Americansdespite life circumstancesthat are materially moredifficult.Moreover, political andcultural life in theMiddleAgeswaslargelyorganizedto minimize, eveneliminate, the sorts ofsocial uncertainties we

contendwithtoday.“Fromthemoment of birth,” thepsychoanalystandpoliticalphilosopher Erich Frommobserved, “[the medievalperson] was rooted in astructuralized whole, andthus life had a meaningwhichleftnoplace,andnoneed, for doubt. A personwasidenticalwithhisrolein society; he was apeasant, an artisan, a

knight, and not anindividualwhohappened tohave this or thatoccupation.” Oneargument forwhy twenty-first-century life producesso much anxiety is thatsocial and political rolesare no longer understoodto have been ordained byGod or by nature—wehave to choose our roles.Such choices, research

shows, are stressful. Assodden with fear anddarkness and death as theMiddleAgeswere, Frommand others argue, theywerelikelyfreerofanxietythanourowntimeis.The “dizziness offreedom,” as Kierkegaarddescribed it, produced bythe ability to makechoices, canhavepoliticalimplications: it can

generateanxietysointensethat it creates a yearningtoreturntothecomfortingcertainties of the primaryties—a yearning for whatFromm called “the escapefrom freedom.” Frommargued that this anxietyled many working-classGermans to willinglysubmit to Hitler in the1930s. Paul Tillich, atheologianwhogrewupin

Weimar Germany,similarlyexplainedtheriseofNazismasaresponsetoanxiety. “First of all afeeling of fear or, moreexactly, of indefiniteanxietywasprevailing,”hewrites of 1930s Germany.“Not only the economicand political, but also thecultural and religious,securityseemedtobelost.There was nothing on

which one could build;everything was withoutfoundation.A catastrophicbreakdown was expectedevery moment.Consequently, a longingfor security was growingin everybody. A freedomthat leads to fear andanxiety has lost its value;better authority withsecuritythanfreedomwithfear.” Herbert L.

Matthews, a New YorkTimes correspondent whocovered Europe betweenthe wars, also observedthat Nazism providedrelief from anxiety:“Fascism was like a jailwheretheindividualhadacertainamountofsecurity,shelter, and daily food.”Arthur Schlesinger, Jr.,writing a few years afterthe end of the Second

World War, observed thesame thing about SovietCommunism: “It has filledthe ‘vacuum of faith’caused by the waning ofestablished religion; itprovides the sense ofpurpose which healsinternalagoniesofanxietyand doubt.” In periods ofsocialdisruption,whenoldverities no longer obtain,there’s a danger that, as

Rollo May put it, “peoplegrasp at politicalauthoritarianism in theirdesperate need for relieffromanxiety.”One implication of the

neurobiologist RobertSapolsky’s work is thathumansocialandpoliticalsystems that are highlyfluid and dynamicgenerate more anxietythan systems that are

static. Sapolsky points outthat “for 99 percent ofhuman history” societywas “most probablystrikingly unhierarchical”andthereforeprobablylesspsychologically stressfulthan in the modern era.Forhundredsofthousandsofyears,thestandardformof human socialorganization was thehunter-gatherertribe—and

such tribes were, judgingfromwhatweknowofthebands of hunter-gatherersthat still exist today,“remarkably egalitarian.”Sapolsky goes so far as tosay that the invention ofagriculture, a relativelyrecent development in thescope of human history,“was one of the greatstupidmovesof all times”because it allowed for the

stockpilingoffoodand,forthe first time in history,“the stratification ofsociety and the inventionof classes.” Stratificationcreated relative poverty,making possible theinvidious comparison andproducingtheoccasionforstatusanxiety.Jerome Kagan, among

others, has argued thathistorical changes in the

nature of human societyhave led to mismatchesbetween our evolutionaryhardwiring and whatmodern culture values.Qualitiessuchasexcessivetimidity, caution, andconcernwith the opinionsof others that would havebeen socially adaptive inearly human communitiesaremuch“lessadaptiveinan increasingly

competitive, mobile,industrialized, urbansociety than these traitshadbeenseveralcenturiesearlier in a rural,agricultural economy ofvillagesandtowns,”Kaganwrites. In preliteratecultures, allmembers of acommunity generallyshared the same valuesand sources of meaning.But starting sometime

around the fifth centuryB.C., humans haveincreasingly lived incommunities of strangerswith diverse values—atrend thathyperaccelerated duringtheRenaissanceandagainduring the IndustrialRevolution. As a result,and especially since theMiddle Ages, “a differentkind of uncomfortable

feeling was evoked byreflectionontheadequacyofself’sskillsorstatusandthevalidityofone’smoralpremises,” Kagan argues.“These feelings, whichwere labeled anxiety,ascendedtothepositionofthe alpha emotion in thehierarchy of humanaffects.” Perhaps thehuman organism is notequipped to live life as

societyhas latelydesignedit—a harsh zero-sumcompetition where theonlygainstobehadareatthe expense of someoneelse, where “neuroticcompetition”hasdisplacedsolidarityandcooperation.“Competitiveindividualism militatesagainst the experience ofcommunity, and the lackof community is a

centrally important factorin contemporaneousanxiety,” Rollo Mayarguedin1950.By 1948, when W. H.

Auden won the PulitzerPrize for The Age ofAnxiety, his six-part poemdepicting man adrift (“asunattached astumbleweeds”) in anuncertainindustrialworld,anxiety seemed to have

leachedoutoftherealmofpsychiatry to become ageneral cultural condition.During the 1950s, withAmerica newly ascendantafter the Second WorldWar, the best-seller listwas already stippled withbooks about how toachieve nervous relief. Onthe heels of DaleCarnegie’s best-selling1948HowtoStopWorrying

and Start Living came apassel of books bearingtitles like Relax and LiveandHow to Control Worryand Cure Your NervesYourself and The Conquestof Fatigue and Fear,suggesting that Americawas in the grip of whatone social historian called“a national nervousbreakdown.”OnMarch31,1961, a Time magazine

cover story (featuring animage of Edvard Munch’sThe Scream) declared thatthe present era “is almostuniversallyregardedastheAge of Anxiety.” TheBritishandAmericanbest-seller lists of the 1930s, amuchmore unstable time,were similarly populatedwithself-helpbooksabout“tension” and “nerves.”Conquest of Nerves: The

Inspiring Record of aPersonal Triumph overNeurastheniawent throughmultipleprintings in1933and1934.YouMustRelax:A Practical Method ofReducing the Strains ofModern Living, a book byan American physiciannamed Edmund Jacobson,reachedthetopoftheNewYork Times best-seller listin1934.

In linking anxiety touncertainty, Auden wasboth falling into a longhistorical tradition andanticipating modernneuroscience. One of theearliest uses of the word“anxiety” in Englishassociated it with chronicuncertainty: theseventeenth-centuryBritish physician and poetRichard Flecknoe wrote

that the anxious person“troubles herself withevery thing” or is “anirresolute person” who“hoversinhiseverychoicelike an empty Ballancewith no weight ofJudgmenttoinclinehimtoeither scale.… When hebegins to deliberate henevermakesanend.”(Thefirst among the OxfordEnglish Dictionary’s

definitions of “anxiety” is“uneasiness about someuncertainevent”[emphasisadded].) Recentneurobiologicalinvestigations haverevealed that uncertaintyactivates the anxietycircuits of the brain; theamygdalae of clinicallyanxious people areunusually sensitive touncertainty. “Intolerance

of uncertainty appears tobe the central processinvolved in high levels ofworry,”MichelJ.Dugas,apsychologistatPennState,has written. Patients withgeneralized anxietydisorder “are highlyintolerant of uncertainty,”he says. “I use themetaphor of ‘allergy’ touncertainty … to helpthem conceptualize their

relationship withuncertainty.” Between2007and2010, therewasa 31 percent increase inthe number of newsarticles employing theword “uncertainty.” Nowonderwe’resoanxious.

Except maybe we’rerelativelylessanxiousthanwe think. Because if you

read far enough back intothe cultural history ofnervousness andmelancholy, eachsuccessive generation’sclaim to be the mostanxious starts to soundmuchliketheclaimsofthegenerations that precededand followed it.When theBritish physician EdwinLee, writing in A Treatiseon Some Nervous Disorders

in 1838, argued that“nervous complaintsprevail at the present dayto an extent unknown atany former period, or inany other nation,” hesounds not only likeGeorge Miller Beard afterhim but also like theBritish naval surgeonThomas Trotter beforehim. “At the beginning ofthenineteenthcentury,we

do not hesitate to affirmthat nervousdisorders … may now bejustly reckoned two thirdsof the whole with whichcivilized society isafflicted,”Trotterwrote inA View of the NervousTemperament, published in1807.aEightyyearsbeforeTrotter, George Cheyne,themostprominent“nervedoctor” of his day, argued

that the “atrocious andfrightful symptoms”of thenervous affliction he haddubbed “the EnglishMalady” were “scarceknown to our ancestors,and never r[ose] to suchfatalheightsnorafflict[ed]such numbers and anyotherknownnation.”bSome intellectualhistorians have traced thebirthofmodernanxietyto

the work of theseventeenth-centuryOxford scholar RobertBurton.c Burtonwas not adoctor,andhescarcelylefthis study, so busy was hefordozensofyearsreadingastonishingly widely andscribbling away at hismammoth tome, TheAnatomyofMelancholy,buthis influence on Westernliterature and psychology

has been lasting. SirWilliamOsler,theinventorof the medical residencysystem and one of themost influentialdoctorsofthe late nineteenthcentury, called TheAnatomy of Melancholy“the greatest medicaltreatise ever written by alayman.” John Keats,CharlesLamb,andSamuelTaylor Coleridge all

treasureditanddrewonitfor their own work.Samuel Johnson, for hispart, told James Boswellthat itwas“theonlybookthat ever took him out ofbedtwohourssoonerthanhe wished to rise.”Completed in 1621, whenBurton was forty-four andthenrevisedandexpandedmultiple times over thefollowing seventeen years,

TheAnatomyofMelancholyis an epic work ofsynthesis that rangesacross all of history,literature, philosophy,science, and theology upto that time. Originallypublished in threevolumes,theworkswelledas Burton tinkered andadded (and added somemore) in the years beforehisdeathin1640;myown

copy, a paperbackfacsimile of the sixthedition, is 1,382 pages ofverysmalltype.Much of what Burtonwrites is absurd,nonsensical, self-contradictory, boring, inLatin, or all of the above.But it is also full of goodhumoranddarkpessimismand consoling wisdomaboutthehumancondition

(it’s easy to see whySamuel Johnson was sotaken with it), and in hisexuberant travels throughwhatseemslikeeverythingever written, he managedto gather all of the extanthuman knowledge aboutmelancholy in a singlework and to establish forlater writers and thinkersthe terrain on which theywould operate. The work

isalsoclearlyinformedbyhis own depression and,like Augustine’sConfessions and Freud’sInterpretation of Dreams,draws insight not onlyfrom the expert testimonyofothersbutfromhisowndeep introspection. “Othermen get their knowledgefrom books,” hewrites. “Iget mine frommelancholizing.” Of

course, a lot of Burton’sknowledge does comefrom books—he citesthousands of them—andpart of what makes thebook so interesting isBurton’s ability toobjectify his subjectiveexperience.dThoughpartsofBurton’s

book were alreadyoutdated and ridiculouswhen he published it,

some of his insights andobservations are quitemodern. His clinicallyprecise description of apanic attack would passmuster with the DSM-V:“Many lamentable effectsthis fear causeth in men,astobered,pale,tremble,sweat; it makes suddencoldandheattocomeoverallthebody,palpitationofthe heart, syncope, etc.”

And here’s a passabledescription ofwhatwouldtoday be diagnosed asgeneralized anxietydisorder: “Many men areso amazed and astonishedwith fear, they know notwhere theyare,what theysay, what they do, andthat which is worst, ittortures them many daysbefore with continualaffrights and suspicion. It

hinders most honourableattempts, and makes theirhearts ache, sad andheavy. They that live infear are never free,resolute, secure, nevermerry, but in continualpain: that, as Vives trulysaid,Nullaestmiseriamajorquam metus, no greatermisery, no rack, nortorture like unto it; eversuspicious, anxious,

solicitous, they arechildishly droopingwithout reason, withoutjudgment, ‘especially ifsome terrible object beoffered,’ as Plutarch hathit.”eBurton piles up

hundreds upon hundredsof theories about anxietyand depression, many ofwhich contradict eachother, but in the end the

treatments he emphasizesmight be boiled down togetting regular exercise,playing chess, takingbaths, reading books,listening to music, usinglaxatives, eating right,practicing sexualmoderation, and, aboveall,keepingbusy.“Thereisno greater cause ofmelancholy than idleness,‘no better cure than

business,’ ” he wrote,citing the Arabianphysician Rhasis.Channeling thewisdomofthe Epicureans and theStoics(and,fromtheEast,the Buddhists), he advisesmodesty of ambition andanacceptanceofwhatonehasasapathtohappiness:“Ifmenwould attempt nomore than what they canbear, they should lead

contented lives and,learning to knowthemselves, would limittheirambition;theywouldperceive then that naturehath enough withoutseeking such superfluitiesand unprofitable things,which bring nothing withthem but grief andmolestation.Asa fatbodyismoresubjecttodiseases,so are rich men to

absurdities and fooleries,to many casualties andcrossinconveniences.”

Tryingtodirectlycomparelevels of anxiety betweeneras is a fool’s errand.Modern poll data andstatistics about rising andfalling levels oftranquilizer consumptionaside, there is no magical

anxiety meter that cantranscend the culturalparticularitiesofplaceandtime to objectivelymeasure levels of anxiety—which,likeanyemotion,is in some sense aninherently subjective andculturallyboundthing.Butif anxiety is a descendantof fear, and if fear is anevolutionary impulsedesigned to help prolong

thesurvivalofthespecies,then anxiety is surely asold as the human race.Humans have always andeverbeenanxious(even ifthat anxiety gets refractedin different ways indifferent cultures); somerelatively fixed proportionof us have always beenmore anxious than others.As soon as the humanbrain became capable of

apprehendingthefuture,itbecame capable of beingapprehensive about thefuture.Theabilitytoplan,the ability to imagine thefuture—with these comethe ability to worry, todread the future.DidCro-Magnons suffer nervousstomachs when predatorslurked outside the cave?Did early hominids findtheirpalmsgettingsweaty

andtheirmouthsdrywheninteracting with higher-status members of thetribe? Were thereagoraphobic cavemen orNeanderthalswhoenduredperformance anxiety orfear of heights? I imaginethere were, since theseproto–Homo sapiens werethe products of the sameevolution that hasgenerated our own

capacity for anxiety, andthey possessed the same,or very similar,physiological equipmentforfear.Which suggests thatanxiety is an abiding partof the human condition.“Inourdaywestillseeourmajor threats as comingfromthetoothandclawofphysical enemies whenthey are actually largely

psychological and in thebroadest sense spiritual—that is they deal withmeaninglessness,” RolloMaywrote in 1977 in theforeword to his revisededition of The Meaning ofAnxiety.“Wearenolongerprey to tigers andmastodons but to damageto our self-esteem,ostracismbyourgroup,orthe threat of losing out in

the competitive struggle.The form of anxiety haschanged, but theexperience remainsrelativelythesame.”

* Anxiety seems to be woven intotheAmericanspirit—asAlexisdeTocqueville observed as early asthe 1830s. “Life would have norelishforthe[peoplewholiveindemocracies] if they were

delivered from the anxietieswhich harass them, and theyshow more attachment to theircares than aristocratic nations totheir pleasures,” he wrote inDemocracyinAmerica.

†Italsoproduceddrugdependence.Just as the postwar affluence ofthe 1950s would lead to thefrantic gobbling of Miltown,Librium, and Valium, thecompetitive pressures of the latenineteenth century produced an

alarming rise in the number of“opiate eaters.” Writing inConfessionsofanAmericanOpiumEater:FromBondagetoFreedomin1895,HenryG.Cole argued that“our mechanical inventions, thespread of our commerce … ourambitionforpoliticalhonors;andgraspingforpettyofficesforgain;ourmad race for speedywealth,which entails feverishexcitements…[and]agrowthsorapid, and in some ways so

abnormal, [have combined toproduce]thementalstrain[that]has been too much for thephysical system to bear; tillfinally,theoverworkedbodyandthe overtaxed bodymust… findrestintherepeateduseofopiumormorphine.”

‡ Elsewhere, Beard wrote thatanxiety was “modern, andoriginallyAmerican; and no age,no country, and no form ofcivilization, not Greece, not

Rome, nor Spain, nor theNetherlands, in their days ofglory,possessedsuchmaladies.”

§ Some years earlier, the elites ofGeorgian Britain—the periodextending from the early 1700suntilQueenVictoria ascended tothethronein1837—hadadopteda similar “nervous culture,”whichclaimedforitselfthesamekind of self-flattering classconnotations that would becharacteristic of American

neurasthenia: the idea that thenervoussystemsofthoseofbetterbreeding and more creativesensibilities were unusuallysusceptible to hypochondriasisand nervous collapse. Thisculture, like that of theRenaissance, tendedtoglamorizeindividualswithsensitivenervoussystems while providing bothmedical and psychologicalexplanations for their delicateconstitutions. As anatomists

continuedtounlockthesecretsofthe human nervous system,scientists of this era variouslydescribedthenervenetworkasasystem of fibers, strings, pipes,andcords,venturingexplanationsthat attributed the system’sfunctioning to hydraulics,electricity, mechanics, and soforth. The crucial concept in allthese explanations was thenervous breakdown—the ideabeing that when the nervous

systemwasoverstrained,itwouldbreak down, producing bothmental and physical symptomsand often general prostration.Beginning in the 1730s, themalfunctions of the nervoussystem that led to breakdownwere often called “nervousdistempers,” which encompassedeverything from hysteria andhypochondria to “the vapors”—mental and physical complaintsthat inmore recent timeswould

be labeled psychoneurotic orpsychosomatic.

Instrikingcontrast tothestiff-upper-lip ideals of the Victorianerathatwouldfollow,theBritishelites of the eighteenth centurywallowedin,andevencultivated,their nervous disabilities.“Nervous self-fashioning”—painting oneself as the victim ofone’snerves—wascommon.From1777 to 1783, James Boswell,Samuel Johnson’s biographer,

wrote a monthly essay for TheLondon Magazine under the pennametheHypochondriack,andinhis own diary he minutelytracked every subtle shift in hisendless litany of emotional andphysical symptoms. Boswell wasobsessed with his digestivesystem.“FromthisdayfollowMr.[John] Locke’s prescription ofgoingtostooleverydayregularlyafter breakfast,” he wrote in hisjournalearlyinOctober1764.“It

willdoyourhealthgood,anditishighly necessary to take care ofyour health.” (Yes, that JohnLocke—the one who wrote TwoTreatisesofGovernmentandisthefatherofconstitutionalliberalism.MostpeopleturntoLockeforhisthoughts on political philosophy;Boswell did so for his advice ondigestive hygiene. If you’recuriouswhatLocke’sprescriptionwas,well, sowas I—so I trackeditdown,andhere’swhat I found

in section 24 of Some ThoughtsConcerning Education: “If a man,after his first eating in themorning, would presently solicitnature,andtrywhetherhecouldstrain himself so as to obtain astool, he might in time, byconstant application, bring it tobehabitual.”)

Nervous disorders of variouskinds were believed to be sowidespreadduringthistimethat,despite the various physiological

explanationsgivenforthem,theywere viewed as a culturalcondition as much as a medicalone. One prominent Britishphysician claimed that a thirdofthepopulationwas“destroyedormademiserablebytheDiseases.”(Thepopularityofnervousillnessduringthistimewasnotconfinedto England. In 1758, JosephRaulin, thepersonalphysician toLouis XV of France, wrote that“the vapors” had become “a

veritable social plague, anendemic disease in the cities [oftheContinent].”)

‖Thisisnotsurprising,consideringthat panic attacks did notofficially exist until thepublication of the DSM-III in1980.

aTrotterwarnedthatan“epidemic”of nervousness threatened notonly the “national character” ofBritain but also its nationalsecurity, since in theirweakened

states, British citizens were ripeforbeinginvadedandconquered.(Trotter’s fears about thecountry’s epidemic of nervousweakness were intensified byNapoleon, who was maraudingaroundtheContinent.)

bCheyneclaimedthatathirdoftheBritish population was afflictedwith the nervous conditionknownvariouslyas“spleen,”“thevapours,” or “hypochondria”—whatwouldtodaybeclusteredin

theDSM under the umbrellas ofthe anxiety or depressivedisorders. (Note that Cheyne isclaiming a level of anxiousaffliction for the England of the1730sthatiscomparabletowhatthe National Institute of MentalHealthclaimsforAmericatoday.)

cCitingthereportsofotherwriters,Burton claimed that thefrequencyofmelancholia—whichsubsumed the modern diagnosesofbothanxietyanddepression—

was “so common in this crazedageofours”that“scarceoneinathousandisfreefromit.”

d I feel a kinship with Burtonbecause he freely conceded thathe wrote about melancholy tocombat his own: “I write ofmelancholy, by being busy toavoid melancholy.” (I write ofanxietytoavoidbeinganxious.)

e Plutarch, the biographer andhistorian, described vividly andaccurately how what we would

todaycallclinicaldepressioncanbring with it an escalation ofanxiety.Anyonewhohassufferedthe torturous insomnia ofagitated depression—whereanxiety begets sleeplessness andsleeplessnessbegetsmoreanxiety—will recognize the clinicalaptness of Plutarch’s description.To the depressed person, hewrites, “every little evil ismagnifiedbythescaringspectresofhisanxiety.…Asleeporawake

he is haunted alike by thespectresofhisanxiety.Awake,hemakes no use of his reason; andasleep,heenjoysnorespite fromhis alarms. His reason alwaysslumbers; his fears are alwaysawake. Nowhere can he find anescape from his imaginaryterrors.”

Plutarchwasnotaphysician—but Galen, born not long afterPlutarchdied,was.Describinganepidemic of anxiety that sounds

remarkablymodern,Galenwroteof having seen “tremors in thehearts of healthy young peopleand adolescents weak and thinfromanxietyanddepression”andpatients with “scarce, turbulent,and interrupted sleep,palpitations, vertigo” and“sadness,anxiety,diffidence,andthebeliefofbeingpersecuted.”

PARTV

RedemptionandResilience

CHAPTER11

Redemption

The capacity to bearanxietyisimportantforthe individual’s self-realization and for hisconquest of his

environment.… Self-actualization occursonly at the price ofmoving ahead despitesuch shocks. Thisindicates theconstructive use ofanxiety.—KURTGOLDSTEIN,HumanNatureinthe

LightofPsychopathology

(1940)

Starting when I was tenyears old, I saw the samepsychiatrist once or twicea week for twenty-fiveyears. Dr. L. was thepsychiatrist who, when Iwas taken to McLeanHospital as acomprehensively phobic

ten-year-old, administeredmyRorschachtest.WhenIstarted therapy with himintheearly1980s,hewasapproaching fifty, tall andlanky,baldingalittle,witha beard in the classicFreudian style. Over theyears, thebeardcameandwent a few times, and helost more of his hair,which turned, over time,from brown to salt-and-

peppertowhite.Hemovedhis office from one place(where he lived with hisfirst wife) to another(where he lived with hissecond wife) to a third(where he leased spacefrom an eye doctor) to afourth (where, in keepingwith his migration in aNew Age direction, heshared a waiting roomwith a massage therapist

and an electrologist) to,finally, the last time Ivisited him, a building bythe ocean on Cape Cod(where he’d moved hispractice and where hisoffice is once againconnectedtohishouse).Trained at Harvard in

the1950sandearly1960s,Dr.L.cameofprofessionalage in the late stages ofthepsychoanalyticheyday,

when Freudianism stilldominated. When I firstencounteredDr.L.,hewasa believer both inmedication and in suchFreudian concepts asneurosis and repression,Oedipus complexes andtransference. Our firstsessions, in the early1980s, were filled withRorschach tests and free-associatinganddiscussions

ofearlymemoriesfrommyyoungest years. Our lastsessions,inthemid-2000s,were focused on role-playing and “energywork”; he also spent a lotoftimeduringthoselatteryears trying to get me tosign up for a special kindof yoga program that istoday defending itself infederal court againstmultipleallegationsthat it

isabrainwashingcult.Here’s someofwhatwe

did in our sessionstogether over a quartercentury: looked at picturebooks (1981); playedbackgammon (1982–85);played darts (1985–88);experimented sporadicallywith various cutting-edgepsychotherapeuticmethodsofaprogressivelymore New Age

complexion, such ashypnotism, facilitatedcommunication, eyemovement desensitizationand reprocessing, inner-child therapy, energysystems therapy, andinternal family systemstherapy (1988–2004). Iwas the beneficiary, orpossibly the victim, ofseemingly every passingtrend in psychotherapy

andpsychopharmacology.A few years ago, when

embarkingontheresearchfor thisbook, Idecided totrack down Dr. L. for aninterview. His inability tocure me notwithstanding,who better to help mefigureoutmyanxietythanthemanwho hadworkedfordecadestotreatme?SoIwrote tohim to tell himwhatIwasworkingonand

toask if Imight interviewhimaboutmymanyyearsof therapy with him andlookatanyoldcasefilesofmine he still had.He saidhe didn’t have my filesanymorebutthathewouldbe happy to talk. So on acold afternoon in lateNovember, I drove fromBoston out the length ofCapeCodtoProvincetown,briskandbarrenintheoff-

season. It had been morethan five years since I’dlastseenorspokentohim,and I was anxious (ofcourse) about how themeeting would go.Wanting to maintain ajournalistic composure—and to avoid falling intoold dependent habits ofrelating tohim (he’dbeena father figure for twenty-five years)—I popped a

Xanax beforehand andbrieflyconsideredstoppingat a liquor store for asedating nip of vodka.* Ipulledintohisdrivewayinthemidafternoon.Waiting on his back

deck, he waved andgestured me up the stepsand into his office, wherehegreetedmewarmly,ifalittle warily, wondering, Isuspect, if I had come to

gather evidence for amalpractice suit. (His e-mail correspondenceleadinguptothismeeting,aboutmycasefilesandsoforth, had all seemedcarefully worded, asthough vetted by alawyer.)Bytheninhislateseventies, he still lookedlithe and fit and appearedyoungerthanhisyears.WesatdownandIcaughthim

uponwhatI’dbeendoingthe past few years, andthen we began talkingaboutmyanxiety.What, I asked, did he

remember about my casefrom when I originallyshowed up at thepsychiatric hospital morethantwodecadesearlier?“I remember it pretty

clearly,” he said. “Youwere a very distressed

child.”I asked him about my

emetophobia, which hadalready presented itselfforcefully by the time Iwasten.“Itwasadramaticfantasy that vomitingwould make your bodycome apart,” he said.“Your parents didn’t helpyoutoreality-test,andyoumergedwiththatphobia.”Did he remember how

he and the team at thementalhospitalinterpretedmy Rorschach test? I hadrecently approached therecords department atMcLean Hospital to askwhether archivists couldfind my originalevaluation file, but it hadbeen moved off-site someyearsago,andnoonehadbeenabletotrackitdown.The only image I could

recall was one that Irememberedlookinglikeawounded bat, its wingstorn, unable to escapefrom its cave. “That likelyhad something to dowithyour feelings of beingabandoned or beingenveloped,”Dr.L.said.“Asenseof lackofsafetyandof enormousvulnerability.”I asked him what he

thoughthadproducedthatvulnerability.“Therewasawholehostofcausalfactors.Weknewthere were deficits in theparents.”He spoke firstaboutmyfather, whom he knewvery well, havingcounseled him when mymother left him for themanaging partner of herlawfirm.†“Whenyouwere

growing up, your fatherhad a very strong‘knower,’ which meantthatpartsofhimself stoodstrongly in judgment. Hedidn’t have a lot oftolerance for anxiousbehavior. Your anxietywould make him blow upwith anger. He had noempathy. When you gotanxious,hewouldjudgeitand want to fix it. He

couldn’t just help you sitwithit.Hecouldn’tsootheyou.”Dr. L. paused for a

moment. “He couldn’tsoothe himself, either. Hewouldjudgehisanxiety.Inhis mind, anxiety isweakness. It makes himangry.”‡Whataboutmymother?“She was too anxious

herselftobeveryeffective

at helping you cope withyour own anxiety,” Dr. L.said. “She organized herlifearoundtryingnottobeanxious. So when you gotanxious, she would getanxious. A parent-childunit like that, the childtakesontheanxietyoftheparent but doesn’t knowwhere it came from. Heranxietybecameyours,andyoucouldn’thandleit,and

shecouldn’thelpyou.“Youhadproblemswith‘object constancy,’ ” hecontinued. “You couldn’tcarry an internal imageofyour parents. Wheneveryouwereawayfromthem,you were in fundamentaldoubt about whether youwere being abandoned.Your parents could neversettledownenoughtogiveyou the assurance they

wereontheplanet.”§Dr. L. said he believedthisseparationanxietywascompounded by mymother’soverprotectiveness. “Themessageyougotfromyourmotherwas,Youcan’ttakeit—don’t take risks becausethe anxiety will be toooverwhelming.”I tell him it sounds likehe’smainlyattributingmy

anxiety to psychodynamicissues—to the relationshipIhadwithmyparents.Butdoesn’t modern researchsuggest that vulnerabilityto anxiety is largelygenetic? Doesn’t, forinstance, Jerome Kagan’sworkonthelinksbetweengenes and temperament,andbetween temperamentand anxiety, suggest thatanxious character is

hardwired into thegenome?“Look,maybehavingan‘inhibited temperament’made things worse foryou,” he said. “But myown view is that even ifyou hadn’t had that kindof genetically producedtemperament, yourmother’spersonalitymightstillhavegivenyouissues.Neither she nor your

father could offer whatyou needed. You couldn’tsootheyourself.“Yes,” he continued,“there’s evidence thatyou’ve got neurochemicalproblems produced byyour genes. And yourmother’spersonalitywasabadmatchforyourgenetictemperament. But a genepredisposing you to anillness doesn’t necessarily

give you that illness.Geneticistssay,‘We’llmapthegenesandfindoutthetrouble.’No!Nottrue!Evenwith breast cancer,sometimes only anenvironmental factor—likenutrition—will catalyze agenetic predisposition tocancerintoactualcancer.”I observe that

medication—Xanax,Klonopin, Celexa, alcohol

—is more effective atsoothing me than myparentseverwere,orthanDr.L.was,orthanmyownself-will (whatever thatmayconsistof) is.Doesn’tthat suggest that myanxiety is a medicalproblem more than apsychological one,regardless of what myparents’shortcomingsmayhavebeen?Thatanxietyis

a problem embedded inthe body, in the physicalbrain rather than somedisembodied mind orpsyche—a problem thatleaches up from body tobrain to mind rather thanseeping down from mindtobraintobody?“False dichotomy!” hesays emphatically,standinguptopullabookoff his shelf: Descartes’

Error.Init,theneurologistAntonio Damasio explainsthat Descartes was wrongtoarguethatthemindandbody are distinct. Themind-bodydualityisnotinfact a duality, Dr. L. says,paraphrasing Damasio.Thebodygives rise to themind;themindimbuesthebody. The two cannot bedifferentiated.“Neocorticalfunction”—that is, the

mind—“makes us who weare,” Dr. L. says. “But thelimbic system”—which isautonomic andunconscious—“maybejustasrelevant,ifnotmore,indetermining who we are.The neocortex can’t makea decision without theemotional system playingin.”To illustrate the

inseparability of body and

mind, Dr. L. talked aboutthe effects of trauma. (Hehad recently been to SriLanka, where he coachedpsychotherapists on howto work with survivors ofthe 2004 tsunami.) Theexperience of trauma orabuse, he explained, getsstoredinthebody,“wovenintothebodilytissue.”“Consider Holocaust

survivors,” he said. “Even

grandkids of Holocaustsurvivors carry extraanxiety that ismeasurableat a physiological level.They tend to have moreanxious triggers. If theysee a movie with victimsof violence in Somalia,they respond to it muchmore strongly.” This istrue, he said, not just ofthe children of Holocaustsurvivors but of their

grandchildren and evengreat-grandchildren.“They’ve got somethingplastered into their bodiesvia theexperienceof theirparents or grandparents.The trauma doesn’t evenbelong to them, but itaffectsthem.”(Ithinkhereof my father’s Holocaustfixation, the books aboutNazis piled always on hisbedside table, the World

War II documentariesalwaysrunningontheTV.Hismotherandfatherhadescaped Germany beforetheHolocaust;sodidmuchof the rest of the family,but not before his unclesand grandfather werebeaten up onKristallnacht.)IaskedDr.L.howmuchhe thought the psychiatricfieldhadchangedsincehe

entereditnearlyfiftyyearsago, especially regardingits thinking about thecauses and treatment ofanxiety.“Freudians were about‘insight’ über alles,” hesaid. “If you had insightabout your neurosis, theexpectation was that youcouldcontrolit.Wrong!”Dr. L.’s treatments ofchoice these days are,

depending on your pointof view, either high-techand cutting-edge or NewAge and weird: forinstance, eye movementdesensitization andreprocessing, whichinvolvesmovingyoureyesback and forth whilereliving a trauma, andinternal family systemstherapy, based on thework of the psychiatrist

Richard Schwartz, whichinvolves training a patientto gain control of hismultiple selves throughthe “conducting self” andhelping him to develop abetter,more strengtheningrelationship with hisvulnerable inner child. Inmy latter years of therapywithDr.L.,Ispentalotoftimemovingfromchairtochair in his office,

inhabiting different“selves” and “energies,”and talking to my innerchild.“We used to have amonolithic view of moodandpersonalitydisorders,”Dr.L.continued.“Butnowwe realize we have littlepackets of personality;theyhavetheirownsetsofbeliefs and values.” Thekey to treatment, he says,

is to make the patientconsciousofthesemultipleselves and to help himmanage the selves thatcarrytraumaoranxiety.“Today,” he said, “wenow know much moreabouttheneurocircuitryofanxiety. Sometimes youneed to medicate. Butnewer, better psychiatryalters the brain chemistry—altersitinthesameway

drugsdo.”“Am I doomed by my

neurocircuitry?”Iasked.“Iwent to therapy with youfor twenty-five years, andhave seen multiple othertherapists, and have triedmultiple methods oftreatment. And yet here Iam,advancingintomiddleage, and still sufferingfrom chronic and oftendebilitatinganxiety.”

“No, you’re notdoomed,”Dr.L. said. “Wenow know enough aboutneuroplasticity tounderstand that thecircuitry is alwaysgrowing. You can alwaysmodifythesoftware.”

EvenifIcan’tfullyrecoverfrom my anxiety, I’vecometobelievetheremay

be some redeeming valueinit.Historical evidencesuggests that anxiety canbe allied to artistic andcreative genius. Theliterary gifts of EmilyDickinson, for example,were inextricably boundup with her anxiety. (Shewas completelyhousebound, and in factrarely left her bedroom,

after age forty.) FranzKafka yoked his neuroticsensibility to his artisticsensibility; so, of course,did Woody Allen. JeromeKagan, the Harvardpsychologist, argues thatT. S. Eliot’s anxiety andhigh-reactive physiologyhelped make him a greatpoet. Eliot was, Kaganobserves, a “shy, cautious,sensitive child”—but

because he also had asupportive family, goodschooling, and “unusualverbal abilities,” Eliotwasable to “exploit histemperament” to becomeanoutstandingpoet.Perhaps most famously,Marcel Proust transmutedhisneuroticsensibilityintoart. Marcel’s father,Adrien, was a physicianspecializing in nervous

health and the author ofan influential book calledThe Hygiene of theNeurasthenic. Marcel readhis father’s work, as wellas books by many of theother leading nervedoctors of his day, andincorporated their workinto his; his fiction andnonfiction are “saturatedwith the vocabulary ofnervous dysfunction,” as

one critic has put it. Atvarious points throughoutRemembrance of ThingsPast, characters eithercomment on or embodythe idea that, as Aristotlefirst observed, nervoussuffering can give rise togreat art. For Proust,refinement of artisticsensibility was directlytied to a nervousdisposition.Fromthehigh-

strungcomeshighart.‖From the high-strungcan also come, at leastsome of the time, greatscience.Dean Simonton, apsychologist at theUniversity of California,Davis, who has spentdecades studying thepsychology of genius,estimatesthatathirdofalleminent scientists sufferfromanxietyordepression

or both. He surmises thatthe same cognitive orneurobiologicalmechanisms thatpredispose certain peopleto developing anxietydisordersalsoenhance thesort of creative thinkingthat produces conceptualbreakthroughs in science.When Sir Isaac Newtoninvented calculus, no oneknewaboutitfortenyears

—because he was tooanxious and depressed totell anyone. (For severalyears, he was tooagoraphobic to leave hishouse.) Perhaps if Darwinhad not been forciblyhouseboundbyhisanxietyfor decades on end, hewould never have beenable to finish hiswork onevolution. SigmundFreud’s career was nearly

derailed early on by histerrible anxiety and self-doubt; he overcame it tobecomeacultfigureandamajor intellectualinfluenceongenerationsofpsychotherapists.Once hisreputation as a greatmanof science had beenestablished, Freud and hisacolytessoughttoengravein stone the image of himas the eternally self-

assuredwiseman. But hisearly letters revealotherwise.aNo, anxiety is not, by

itself,goingtomakeyouaNobel Prize–winning poetor a groundbreakingscientist. But if youharness your anxioustemperament correctly, itmight make you a betterworker. Jerome Kagan,who has spent more than

sixtyyearsstudyingpeoplewith anxioustemperaments, believesthatanxiousemployeesarebetter employees. In fact,hesays,helearnedtohireonly people with high-reactive temperaments asresearch assistants.“They’re compulsive, theydon’t make errors, they’recareful when they’recoding data,” he told The

NewYorkTimes.They“aregenerally conscientiousand almost obsessivelywell-prepared.” Assumingtheycanavoidsuccumbingto full-blown anxietydisorders, “worriers arelikely to be the mostthorough workers and themost attentive friends,” asThe Times put it. Otherresearch supports Kagan’sobservation.A 2012 study

by psychiatrists at theUniversity of RochesterMedical Center found thatconscientious people whowere highly neurotictended to be morereflective, more goaloriented, more organized,and better at planningthan average; they tendedto be effective, “high-functioning”workers—andtobebetterat takingcare

of their physical healththan other workers.(“These people are likelytoweightheconsequencesof their actions,” NicholasTuriano, the leadresearcher, said. “Theirlevel of neuroticismcoupled withconscientiousnessprobablystops them from engagingin risky behaviors.”) A2013studyintheAcademy

of Management Journalfound that neuroticscontribute more thanmanagers predicted togroup projects, whileextroverts contribute less,with the contributions ofthe neurotics becomingeven more valuable overtime. The director of thestudy, Corinne Bendersky,an associate professor atUCLA’sAndersonSchoolof

Management, says that ifshe were staffing a teamfor a group project, “Iwould staff it with moreneurotics and fewerextroverts than my initialinstinct would lead me todo.”In2005researchersatthe University of Walespublished a paper, “CanWorriers Be Winners?,”reporting that financialmanagers high in anxiety

tendedtobethebest,mosteffectivemoneymanagers,as long as their worryingwas accompanied by highIQs. Smart people whoworry a lot, theresearchers concluded,tend to produce the bestresults.bUnfortunately, thepositive correlationbetweenworryingand jobperformance disappeared

whentheworriershadlowIQs. But some evidencesuggests that excessiveworrying is itself allied tohigh IQ. Dr. W. says thathis anxious patients tendtobehissmartestpatients.(Inhisexperience,anxiouslawyershave tendedtobeparticularly smart—skillednot only at foreseeingcomplexlegaleventualitiesbut also at imagining

worst-case scenarios forthemselves.) Dr. W.’sanecdotalobservationsaresupported by recentscientific data. Somestudies have found thecorrelation to be quitedirect: thehigheryour IQ,themore likelyyouare toworry; the lower your IQ,the less likely you are toworry. A study publishedin 2012 in Frontiers in

Evolutionary Neurosciencefound that high IQ scorescorrelatedwithhighlevelsof worry in peoplediagnosed withgeneralized anxietydisorder. (Anxious peopleare very smart at plottingout possible badoutcomes.)JeremyCoplan,the lead author of thatstudy, says that anxiety isevolutionarily adaptive

because “every so oftenthere’s a wild-carddanger.” When such adanger arises, anxiouspeople are more likely tobe prepared to survive.Somepeople,Coplansays,are effectively stupidenough that they are“incapable of seeing anydanger,evenwhendangeris imminent”; moreover,“if these folks are in

positions as leaders, theyaregoingtoindicatetothegeneral populace thatthere’snoneed toworry.”Coplan, a professor ofpsychiatry at the StateUniversity of New YorkDownstateMedicalCenter,says that anxiety canbeagood trait in politicalleaders—and that lack ofanxiety can be dangerous.(Some commentators have

suggested, based onfindingslikeCoplan’s,thatthe main cause of theeconomic crash of 2008was politicians andfinancierswhowereeitherstupid or insufficientlyanxiousorboth.)The correlations aren’tuniversal, of course: thereare plenty of brilliantdaredevils and stupidworriers. And, as always,

this comes with theproviso that anxiety isproductivemainlywhen itisnotsoexcessiveastobedebilitating.Butifyouareanxious, perhaps you cantake heart from thegrowing collection ofevidence suggesting thatanxiety and intelligencearelinked.Anxietymayalsobetied

both to ethical behavior

andtoeffectiveleadership.MywifeoncemusedaloudaboutwhatImightloseifIwere to be fully cured ofmy anxiety—and aboutwhat she might lose if Iwere to lose my anxioustemperament.“I hate your anxiety,”

shesaid,“andIhatethatitmakes you unhappy. Butwhat if there are thingsthat I love about you that

are connected to youranxiety? What if,” sheasked,getting to theheartof the matter, “you’recured of your anxiety andyoubecomeatotaljerk?”I suspect I might—becauseitmaybethatmyanxiety lends me aninhibition and a socialsensitivity that make memore attuned to otherpeople and a more

tolerable spouse than Iotherwise would be.Evidently, fighter pilotshave unusually highdivorce rates—a fact thatmaybetiedtotheirhavinglowlevelsofanxietyandacorresponding lowbaseline autonomicarousal, which togetheraretiednotonlytoaneedforadventure(indulgedbyflying a fighter plane or

having extramaritalaffairs) but also to acertain interpersonalobtuseness, a lack ofsensitivity to theirpartners’ subtle socialcues.c Anxious people,becausetheyarevigilantlyscanning the environmentfor threats, tend to bemore attuned thanadrenalinejunkiestootherpeople’s emotions and

socialsignals.The notion of a

connection betweenanxiety and morality longpredates the findings ofmodern science or mywife’s intuition. SaintAugustine believed fearwas adaptive because ithelps people behavemorally. (That’s alsowhatboth Thomas Burgess andCharles Darwin believed

about anxiety andblushing: fear ofmisbehavior helpsprimates and humansbehave “rightly,”preserving social comity.)The pragmatistphilosophers CharlesSanders Peirce and JohnDewey believed that thehuman aversion toexperiencing negativeemotions like anxiety,

shame, and guilt providesa kind of internalpsychological incentive tobehave ethically.Furthermore,psychological studies ofcriminalshavefoundthemto be low in anxiety, onaverage, and to have low-reactive amygdalae.(Criminals also tend tohave lower-than-averageIQs.)

In earlier chapters, Idiscussedhowhundredsofstudies on primatesconducted over the lasthalfcenturyhavefoundinvarious ways that thecombination of certaingenes and small amountsofearlylifestresscanleadto lifelong anxious anddepressive behavior inhumansandotheranimals.But recent studies on

rhesus monkeys byStephen Suomi, the chiefof the Laboratory ofComparative Ethology atthe NIH, have found thatwhen anxious monkeyswere taken in early lifefromtheiranxiousmothersand given to nonanxiousmothers to be raised, afascinating thinghappened: these monkeysgrew up to display less

anxiety than their geneticsiblings—and they also,intriguingly, tended tobecome the alpha males ofthe troop. This suggeststhat some quotient ofanxiety not only enhancesyour odds of living longerbut also, under the rightcircumstances, can equipyoutobealeader.

My anxiety can beintolerable. It oftenmakesme miserable. But it isalso, maybe, a gift—or atleast the other side of acoinIoughttothinktwiceabout before trading in.Perhaps my anxiety islinkedtowhatever limitedmoral sense I can claim.What’s more, the sameanxious imagination thatsometimes drives me mad

with worry also enablesme to plan effectively forunforeseen circumstancesor unintendedconsequences that other,lessvigilant temperamentsmightnot.Thequicksocialjudgingthatisalliedtomyperformance anxiety isalso useful in helping meto size up situationsquickly and to managepeopleanddefuseconflict.

Finally, at some bruteevolutionary level, myanxiety might actuallyhelp keep me alive. I amless likely than you boldand heedless people (youfighter pilots and conartists, with your lowbaseline autonomicarousal) to die in anextreme sporting accidentor to provoke a fight thatleadstomygettingshot.d

In his 1941 essay “TheWound and the Bow,” theliterary critic EdmundWilson writes of theSophoclean heroPhiloctetes, the son of aking, whose suppurating,never-healing snakebitewoundonhisfootislinkedto a gift for unerringaccuracywithhisbowandarrow—his “malodorousdisease” is inseparable

fromhis“superhumanart”formarksmanship.e I havealwaysbeendrawnto thisparable: in it lies, as thenovelist JeanetteWinterson put it, “theproximity of wound togift,” the insight that inweakness andshamefulness is also thepotential fortranscendence,heroism,orredemption. My anxiety

remains an unhealedwound that, at times,holdsmebackandfillsmewith shame—but it mayalsobe,atthesametime,asource of strength and abestower of certainblessings.

*That Ievencontemplated this,ofcourse, suggests that thosedecades of therapy with Dr. L.

were not terribly effective; mydependenciesarenowchemical.

†This, by theway, led to a rathercomplex web of conflicts ofinterest. On the Sunday in theautumn of 1995 thatmymotherannounced to him she mightwant a divorce, my father,desperate to save the marriage,stopped drinking completely forthe first time in years and, in agesture that was completely outof character, acquiesced to

emergency couples’ counseling.For years before that,my father,despite footing the bill for mysister’sandmyshrinks,disdainedpsychotherapy. “How was yourwackolesson?”he’daskjeeringlyafter I’dhadanappointment.Hedid this so often that the termbecame a part of the family’slingua franca,andeventuallymysister and I were referringwithout irony to our wackolessons.(“Mom,canyougiveme

a ride to my wacko lesson onWednesday?”)In1995,Dr.L.hadrecentlyhungoutashingle—withhis new wife, Nurse G.—as arelationship counselor. So myparents began seeing Dr. L. andNurseG.(whowasalsoalicensedclinical social worker) inintensivecouples’therapy.WhichwouldhavebeenfineexceptthatI—by then in my midtwenties—was still seeing Dr. L. as myprincipal psychotherapist. So my

appointments with Dr. L. startedtorunsomethinglikethis:

DR.L.:Howareyou?

ME:Well,Ihadkindofaroughweek.Ihadapanicattackwhen—

DR.L.:Howareyourparentsdoing?

ME:What?

DR.L.:Haveyoutalkedtoyourmotherorfatherinthelastcoupleofdays?Has

yourmothersaidanythingaboutwhethershe’sstillseeingMichaelP.?

Asithappened,mymotherwasstillseeingMichaelP.andinfactwould soon be setting up housewithhim.

Unmoored by my mother’sdeparture, my father startedseeing Dr. L. for psychotherapyon an individual basis. By this

point,wemightaswellhavehadDr.L.onfamilyretainer.Hehadjust provided six months ofmarriage counseling to myparents,was seeingmy father atleast once a week, and was stillseeing me. To make this web ofpsychopathology even moreincestuous, my mother hadstarted seeing Nurse G. on anindividualbasis.

My own therapy sessions withDr. L. came to be dominated by

his questions about his new starpatient, my father. I couldn’tblameDr.L.forfindingmyfatherthe more interesting patient.After all, while he’d been seeingme for more than fifteen years,he’donlybeenseeingmydadfora fewmonths.Beingable to talkto my father about hisrelationshipwithme,andthentotalk tomeaboutmyrelationshipwith my father, surely providedan intriguing Rashomon-like

fascination for Dr. L. He wasseeing my father, his wife wasseeing my mother, he and hiswifewere seeingmymotherandfather together, and he wasseeingme—akaleidoscopicgameof family telephone, with Dr. L.andNurseG. as the switchboardoperators.

My dad entered therapyemotionally wrecked by hisseparation, profoundly shaken,and drinking heavily. He

completed therapy less than twoyears later, happy, productive,remarried, and deemed (byhimselfandbyDr.L.)tobemuchmore “self-actualized” and“authentic”thanhehadbeen.Hewas in and out of therapy withDr. L. in eighteen months.Whereas I was entering mynineteenth year of therapy withDr.L.andwasstillasanxiousasever.

Afewyearsago,mywifeasked

my father what had happenedwhenhegraduated fromtherapywith Dr. L. Had Dr. L. saidanythingaboutmewhenhedid?He had. Dr. L., my fatherrecalled, had told him that Iwasn’t anywhere near ready tograduate and that I had “seriousissues”Istillneededhelpwith.

Which, I suppose, wasmanifestly the case. But wasn’tone of those issues the fact thatmy own father—whose stern

criticalassessmentsofmylifeandwork over the years had likelycontributedtotheleakinessofmyself-esteem—had, in borrowingmytherapistandadvancingfromtemporarybasketcasetocuredinno time at all as I languished inpurgatorial neurotic stasis,confirmed yet again my generalinferiority and incompetence?Whenmyfathergraduated, I feltlikeaschoolchildwhoseyoungersibling has just sped past him in

the accelerated class: my father,starting therapy years (decades!)afterme,shotthroughquicklytograduation with honors, while I,trapped in remedial classes,repeated third grade for thenineteenthtime.

‡ My father’s anger. Among thedarkermomentsofmychildhoodwas this: One night when I wasfourteen, I woke up at three inthe morning with one of mybouts of screaming panic.

Hearing me cry, my father lostcontrol. He stormed into myroom, trailedbymymother,andstarted hitting me repeatedly,tellingme to shutup.Thismademe cry harder. “You twerp, youpathetic littletwerp!”heshoutedas he picked me up and threwme.Ihitthewallandslidtothefloor. As I lay there, racked bysobbing while my father lookeddown at me, I could see mymother standing impassively in

the doorway. I have apredisposition toward feelinglonely evenwhen surrounded byfriends and family; in thatmoment, I felt more lonely thanever before or since. (Here, forconfirmation-of-memorypurposes, is an entry from mydad’s diary, which he begankeepingaftermymotherlefthimandwhichhekindlysharedwithme a few years ago: “At aboutage 11, however, Scott began to

become very anxious and wasparticularly phobic aboutvomiting. He began to manifestsome behavioral oddities thatAnne detected and which Idenied. Anne was right, and,acerbically reviling mypsychological blindness, Dr.Sherry [a pediatric psychiatrist]recommended an evaluation atMcLean. This process led intoScott’s now extendedpsychotherapywithDr. [L.].The

initial rigmarole was terrible,however. Scott got much worseandinparticularcouldn’tsleepatnight. He had to take Thorazineand imipramine. In frustration Ioften got verbally and evenphysicallyabusive.”)

§ This comports with the Bowlby-Ainsworth attachment theoryconceptofthesecurebase.

‖ Consider also such nervousinvalid intellectuals as DavidHume, James Boswell, John

StuartMill, GeorgeMiller Beard,William James, Alice James,Gustave Flaubert, John Ruskin,Herbert Spencer, Edmund Gosse,Michael Faraday, ArnoldToynbee, Charlotte PerkinsGilman, and Virginia Woolf,every single one of whomsuffered debilitating nervousprostration early (and sometimeslate) in their careers. Duringyoung adulthood, David Hume,who would become one of the

bright stars of the ScottishEnlightenment, abandoned hisstudies in the law and entereduponafarmoreprecariouscareerin philosophy. In the spring of1729, following a period ofintense intellectual exertion,Humebrokedown.Hefelt,ashelaterwroteinalettertoadoctordocumenting his ills, physicallyexhausted and emotionallydistraught; he couldn’tconcentrate on the book he was

trying to write (which wouldeventually become the famousTreatiseofHumanNature),andhesuffered terrible stomach pains,rashes, and heart palpitationsthat incapacitated him for thebetterpartoffiveyears.Muchinthe way Darwin later would,Hume sampled the full range ofremedies on offer in the hope offindingacureforwhathecalledhis nervous “distemper”: he tookwater treatments at spas and

went for walks and rides in thecountry; he took the “Course ofBitters and Anti-hysteric Pills”and “an English Pint of ClaretWine every Day” prescribed byhis family’sphysician.Writing toanother doctor in search ofsuccor, Hume asked “whetheramong all those Scholars youhave been acquainted with youhaveeverknownanyaffected inthismanner?Whether I caneverhope for a Recovery? Whether I

must long wait for it? WhethermyRecoverywilleverbeperfect,and my Spirits regain theirformerSpringandVigor,soastoendure the Fatigue of deep andabstruse thinking?” In the event,Hume did recover: after hepublished A Treatise of HumanNature in 1739, he seems not tohave suffered further, and hewent on to become perhaps themost important philosopher evertowriteinEnglish.

The political philosopher JohnStuart Mill endured a similarnervousbreakdown.Inthefallof1826,whenhewas twentyyearsold,Mill experienced a completeemotional collapse, which hewould years later recount in thefamousfifthchapter,“ACrisis inMy Mental History,” of hisautobiography. Through the“melancholywinter”ofthatyear,he was, he writes, in anunrelentingstateof“depression,”

“dejection,” and “dulled nerves.”Hefoundhimselfsoparalyzedbyhis “irrepressible self-consciousness” that he couldscarcely function. (This puts onein mind of the novelist DavidFoster Wallace, another geniusdone in by his acute anxiety.)After eighteen months of thisunremitting misery, Mill wrote,“a small ray of light broke inupon my gloom” while he wasreading thememoirsof aFrench

historian:heneeded,hedecided,to become less repressed andanalytic and to develop hisemotionalandaestheticfaculties.The arduous education imposedon him by his “grim andexacting”fatherhad,herealized,robbed him of a normalchildhood and of an inneremotionallife.“Thecultivationofthe feelings became one of thecardinalpointsinmyethicalandphilosophical creed,” he wrote.

Bybecomingmoreattunedtohisemotions(whichhecultivatedby,forinstance,readingthepoetryofWordsworth), he was evidentlyable to leave anxiety anddepressionbehind.

a Ernest Jones, the originalguardian of Freud’s legacy, onceclaimed that only “uninterestingdetails” had been excised fromthecollectionofFreud’slettershepublished. But among thosestrategically omitted letters were

some 130 to his friend WilhelmFliess,manyofthemconsistingofa litany of neurotic,hypochondriacalcomplaint.

“I have not been free ofsymptoms for as much as half aday,andmymoodandabilitytowork are really at a low ebb,”Freud wrote Fliess in early May1894.Theomittedlettersarefullof symptom reports, repeatedover andover again.Byhisownaccount, Freud sufferedmigraine

headaches, pains all over hisbody, all kinds of stomachdistress, and endless heartpalpitations that led him topredict in one letter that hewoulddie inhisearlyfiftiesofa“ruptured heart.” His (failed)attempts to wean himself fromcigar smoking would cause aresurgenceofphysicalsymptoms:“I feel aged, sluggish, nothealthy.”Whenhisfatherdiedin1896, he reported a seemingly

phobicpreoccupationwithdeath,what he called his “deathdelirium.”

Thisishardlytheimageofthestoical,self-assuredmasterofthemind that he sought to project.“Itistoodistressingforamedicalman who spends every hour ofthe day struggling to gain anunderstandingoftheneurosesnotto know whether he is sufferingfrom a justifiable or ahypochondriacal mild

depression,”FreudtoldFleiss.Hisletters are replete withmelancholic, self-laceratingthoughts:hebelievesthathewilldie inobscurity, thathiswork is“rubbish,” thatallhis laborswillamount to nothing. At times, itseemshecannotpossiblysurvive,let alone thrive, in the field hehaschosen.“Ihavebeenthroughsome kind of neuroticexperience,” he wrote on June22, 1897, plagued by “twilight

thoughts, veiled doubts, withbarely a ray of light here orthere.”

“I still do not know what hasbeenhappeningtome,”henoteda couple of weeks later.“Something from the deepestdepths of my own neurosis setitself against any advance in theunderstandingoftheneuroses.”

InAugust1897,FreudwrotetoFliess from Bad Aussee, Austria,where he was vacationing with

his family.Freudwasnothappy:he was “in a period of badhumor”and“tormentedbygravedoubts about my theory of theneuroses.” His vacation wasdoing nothing toward“diminishing the agitation inmyhead and feelings.” Despite hisgrowing practice, Freud wrote,“the chief patient I ampreoccupiedwith ismyself.”Thefollowing summer, on anothervacation, he reported unhappily

that his work was progressingpoorly and that hewas bereft ofmotivation. “The secret of thisrestlessness is hysteria,” heconcluded remarkably, assigningto himself the affliction that hehadstakedhiscareeroncuring.

b “Anxiety is an importantcomponent of motivatedcognition, essential for efficientfunctioning in situations thatrequire caution, self-disciplineand the general anticipation of

threat,”theresearcherswrote.

c TheAir Force reportedly has thehighest divorce rate in the U. S.armed services, and nine out often fighter-pilot divorces areinitiatedbywives.

d On the other hand, I’m morelikely to die prematurely fromsomestress-relateddisease.

e Wilson’s essay is about how artand psychological suffering arelinked in writers like Sophocles,

Charles Dickens, ErnestHemingway, James Joyce, andEdithWharton.

CHAPTER12

Resilience

Anxiety cannot beavoided, but it can bereduced. The problemof the management ofanxiety is that of

reducing anxiety tonormallevels,andthento use this normalanxiety as stimulationto increase one’sawareness, vigilance,zestforliving.—ROLLOMAY,TheMeaningofAnxiety

(1950)

The essayist, poet, andlexicographer SamuelJohnson was, famously, amelancholic intellectual intheclassicmode, sufferingbadly from what RobertBurton called the “Diseaseof the learned.” In 1729,whenhewastwentyyearsold,Johnsonfoundhimself“overwhelmed with anhorrible hypochondria,with perpetual irritation,

fretfulness, andimpatience; and with adejection, gloom, anddespair, which madeexistence misery,” asJamesBoswell reported inhisLife of Samuel Johnson.“From this dismal maladyhe never afterwards wasperfectly relieved.” (“Thatit was, in some degree,occasioned by a defect inhisnervoussystemappears

highly probable,” Boswellsurmised.) It was, asanother biographerrecords, “an appallingstate of mind, in whichfeelings of intense anxietyalternatedwith feelings ofutter hopelessness.” Manycontemporaries notedJohnson’s strange tics andtwitches, which suggestshemayhavehadOCD.Healso seemed to havewhat

would today be calledagoraphobia. (He oncewrote to the localmagistrate asking to beexcused from jury dutybecause “he came verynear fainting … in allpublic places.”) Johnsonhimself refers to his“morbid melancholy” andwas ever worried that hisdejection would tip overinto full-blown madness.

In addition to dippingregularly into Burton’sAnatomy of Melancholy,Johnson read widely inboth classic andcontemporary medicaltexts.Desperate to hold on tohis sanity, Johnson—likeBurtonbeforehim—seizedon the idea that idlenessand slothful habits werebreeding grounds for

anxiety and madness andthat the best way tocombat them was withsteady occupation andregular habits, such asrising at the same timeearly each morning.“Imagination,” he wouldsay,“nevertakessuchfirmpossessionof themind, aswhen it is found emptyand unoccupied.” So hewas always at pains to

occupy himself and to trytoimposearegimenonhisdaily habits. What mostendears Johnson to me ishis lifelong, and plainlyfutile, attempts to startgetting up earlier in themorning. A representativesampling from hisjournals:

September7,1738:“O Lord, enable

me … in redeemingthetimewhichIhavespentinSloth.”January 1, 1753:

“ToriseearlyTo losenotime.”July 13, 1755: “I

willoncemoreformaschemeoflife…(1)toriseearly.”Easter Eve 1757:

“AlmightyGod … Enable me to

shakeoffsloth.”Easter Day 1759:

“GivemethyGracetobreak the chain ofevil custom. Enableme to shake offidlenessandSloth.”September 18,

1760:“Resolved … To riseearly … To opposelaziness.”April21,1764:“My

purpose is from thistime (1) Toreject … idlethoughts. To providesome usefulamusementforleisuretime. (2) To avoidIdleness. To riseearly.”The next day (3:00

a.m.): “Deliver mefrom the distresses ofvain

terrour … Againstloose thoughts andidleness.”September 18,

1764: “I resolve torise early, Not laterthansixifIcan.”Easter Sunday

1765:“Iresolvetoriseat eight … I purposeto rise at eightbecausethoughIshallnot yet rise early it

will be much earlierthan I now rise, for Ioftenlyetilltwo.”January1,1769:“I

am not yet in a stateto form manyresolutions; I purposeandhopetorise…ateight,andbydegreesatsix.”January 1, 1774

(2:00 a.m.): “To riseat eight … The chief

cause of mydeficiencyhasbeenalife immethodical andunsettled, whichbreaks allpurposes … andperhaps leaves toomuch leisure toimagination.”Good Friday 1775:“When I look backupon resoluti[ons] ofimprovement and

amendments, whichhave year after yearbeen broken … whydoIyettrytoresolveagain? I try becauseReformation isnecessaryanddespairis criminal … Mypurpose is fromEaster day to riseearly, not later thaneight.”January2,1781:“I

will not despair.…Myhope is (1) to rise ateight,orsooner.…(5)toavoididleness.”

Johnson neverwas ableto sustain his early rising,and he spentmany nightsworkinguntilnearlydawnor roaming the streets ofLondon tormented by hisfearsandphobias.*Johnson’s journal

entries, you will havenoted, span more thanforty years—from histwenties until his earlyseventies—anditishardtoknow which is moreaffecting:thefutilityofhisefforts to shake off slothand to rise early or hisearnest commitment tocontinuing to try despitehis knowledge of thatfutility.(Ashewroteinhis

journal on June 1, 1770,“Every Man naturallypersuades himself that hecan keep his resolutions,nor is he convincedof hisimbecilitybutbylengthoftime and frequency ofexperiment.”) WalterJackson Bate, Johnson’sgreatest modernbiographer, first compiledmany of these entries inthe 1970s, when

psychobiography in theFreudian mode was invogue.Batesuggestedthatthese entries—andJohnson’s continuingexhortations to improvehimself generally—wereevidence of a superegothatwastooperfectionisticin its demands, and heargued that the constantberating by Johnson’ssuperego, along with the

low self-esteem thatnaturally accompanied it,accounted for Johnson’s“depressive anxiety” andhis many psychosomaticsymptoms. For Johnson,the “danger” of indolencewas that, as his friendArthurMurphynoted,“hisspirits, not employedabroad, turned inwardwith hostility againsthimself. His reflections on

his own life and conductwere always severe; and,wishingtobe immaculate,he destroyed his ownpeace by unnecessaryscruples.” When Johnsonsurveyed his life, Murphywrote, “he discoverednothingbutabarrenwasteof time, with somedisorders of body, anddisturbancesofmind,verynear to madness. His life,

he says, from his earliestyouth, was wasted in amorning bed; and hisreigning sinwasageneralsluggishness, to which hewas always inclined, and,in part of his life, almostcompelled, by morbidmelancholy and wearinessof mind.” In this strivingforperfectioninorderthathe might think well ofhimself, Johnson exhibits

the classic traits of whatKaren Horney, theinfluential Freudianpsychoanalyst, called theneurotic personality.According to Bate,Johnson’s writing, “whichoftenanticipates … modernpsychiatry,” wasconcerned with “howmuch of the misery ofmankind comes from the

inability of individuals tothink well of themselves,and how much envy andother evils spring fromthis.” As Johnson himselfputit,hisstronginterestinbiography as a literaryform—his work includesThe Lives of the Poets andother biographicalsketches—was motivatedbyaninterestnotsomuchin understanding how a

man“wasmadehappy”orhow“helostthefavourofhis prince” but inunderstanding “how hebecame discontented withhimself.”Buthere’san instructive

fact: As unhappy withhimself as he was, and asfrequently as he beratedhimself for his lassitudeand for lying in bed untiltwo, Johnson was

enormously productive.Johnson, despite churningout essays formoney (“noman but a blockhead”would ever do otherwise,as he famously said), wasnomerehack.Someofhiswritings—his protonovelRasselas, his poem TheVanity of Human Wishes,thebestofhisessays—arefixtures of the Westerncanon. The Works of

Samuel Johnson occupiessixteen thick volumes onmy shelf—and that’s noteven including the workfor which he is mostfamous, the massivedictionary he compiled.Clearly, Johnson’s self-assessments of skillfulnessand accomplishment wereat odds with the reality—which, modern clinicalresearch has shown, is

oftenthecaseinpeopleofmelancholydisposition.†In his persistent efforts

toward self-improvement,andinkeepinguphisgreatwriterly productivity inthe face of emotionaltorment, Johnsonexhibited a form ofresilience—a trait thatmodern psychology isincreasingly finding to bea powerful bulwark

against anxiety anddepression. Anxietyresearch, which hastraditionally focused onwhat’s wrong withpathologically anxiouspeople, is focusing moreand more on what makeshealthypeople resistant todeveloping anxietydisorders and otherclinical conditions. DennisCharney, a professor of

psychiatry andneuroscience at the IchanSchool of Medicine atMount Sinai, has studiedAmericanprisonersofwarin Vietnam who did not,despite the traumas theyendured, becomedepressed or developPTSD.Anumberofstudiesby Charney and othershave found that thequalities of resilience and

acceptance were whatallowed these POWs toward off the clinicalanxiety and psychologicalbreakdown that afflictedmany others. The tencritical psychologicalelements andcharacteristicsofresiliencethatCharneyhasidentifiedare optimism, altruism,havingamoralcompassorset of beliefs that cannot

be shattered, faith andspirituality,humor,havinga role model, socialsupports, facing fear (orleaving one’s comfortzone),havingamissionormeaning in life, andpractice in meeting andovercoming challenges.Separate research hassuggestedthatresilienceisassociated with anabundance of the brain

chemicalneuropeptideY—and while it’s unclearwhich way the causationgoes (does a resilienttemperamentproduceNPYin the brain, or does NPYin the brain produce aresilient temperament, oris it, most likely, acombination of both?),some evidence suggestsNPY levels have a stronggeneticcomponent.‡

I lament to Dr. W. that,based on thirty years offutile effort so far, myprospects for achieving arecovery from anxietysufficientlytranscendenttoprovide an upliftingending to this book seemdismal.Italktohimaboutthe emerging research onresilience, which isfascinating and hopeful—but then I note, as I’ve

done before, that I don’tfeelveryresilient.Infact,Isay, I’ve now got tangibleproof that I’m geneticallypredisposed to be notresilient: I’m biologicallyhardwired, at a cellularlevel, to be anxious andpessimistic andnonresilient.“This is why I keeptelling you I hate all themodern emphasis on the

genetics and neurobiologyofmentalillness,”hesays.“Ithardensthenotionthatthe mind is a fixed andimmutablestructure,whenin fact it can changethroughout the lifecourse.”ItellhimthatIknowallthat. And I know,furthermore, that geneexpression is affected byenvironmental factors and

that, in any event,reducingahumanbeingtoeither genes orenvironment is absurdlyreductionist.Andyet I stilldon’t feelmuch capacity forresilience.“You’re more resilientthan you know,” he says.“You’re always saying ‘Ican’thandlethis’or‘Ican’thandle that.’ Yet you

handle a lot for someonewith anxiety—you handlea lot, period. Just thinkabout what you’ve had todeal with while trying tocompleteyourbook.”As my deadline fordelivering this book creptparalyzingly closer, I tookapart-time leave frommyday job as a magazineeditor so I could focus onwriting. This decisionwas

not without risk:advertising mydispensability at acompany that had beendownsizing, inanindustry(printjournalism)thatwasradically contracting andpossibly dying, and in aneconomy that was theworst since the GreatDepressionwashardly thebest way to maximize myjob security. But

increasingly panicked thatI was going to miss mydeadline and have toplunge my family intobankruptcy, I calculatedthat the leave was anecessary gamble. Myhope was that the timefreed up by going ontemporary leave,combined with thepressure of the loomingdeadline,wouldcreatethe

conditions necessary for aspasmofproductivity.Thatdidn’thappen.Thisdid:The very day that myleave was to begin, myheretoforehealthywifefellill with a mysterious andprotractedailmentthatledto multiple doctor’sappointments (internists,allergists, immunologists,endocrinologists) and a

series of inconclusivediagnoses (lupus,rheumatoid arthritis,Hashimoto’s thyroiditis,Graves’ disease, andothers). A few days afterthat, my completely law-abiding wife was charged(wronglyandabsurdly;it’salongstory)withafelonythat required thousandsofdollars in legal expensesand several trips to court

to combat. Around thissame time, my mother’ssecondhusbandleftherforanother woman, and they(mymother andmy soon-to-be ex-stepfather) begandivorce proceedings that Ifeared would leave herimpoverished. My father’sstart-up company,which Ihad hoped would helpfund my kids’ collegeeducation, lost its funding

andfolded.AndsoasIsatat my computer day afterdayonmyostensiblebookleave, I spent less timewriting than I didworrying about my wife’shealth and compulsivelychecking our dwindlingbank balances as moneyflowed out much fasterthanitwasflowingin.And then one earlymorning in August—the

finalmonthofmyleave—Iawoketocrashingthunderand a driving rain.Suddenly branches andstones started pummelingmybedroomwindow.AsIleapt from bed and ranfrom the room, thewindow exploded inward.(My wife and kids wereout of town.) I made forthe basement, passing thekitchen just as the ceiling

cavedin—atreehadfallenontheroof.Cabinetswereripped from thewalls andpitched to the floor. Lightfixtures dropped fromabove and dangled in theair, suspended by sizzlingwires. A swath ofinsulation unfurled fromwhat remained of theceiling, hanging there likeapanting tongue.Shinglesrained from above,

splattering onto thelinoleum. Rain pouredthroughthegapingholeintheroof.I ran through the livingroom just as another treetoppledontothehouse.Allfourwindows in the roomshattered at once, glassflying everywhere. Dozensoftreeswerefalling,someofthempulledupbytheirroots, others split in two

about eighty feet up fromtheground.I scrambled down thestairs, intending to takerefuge underground. Butwhen I got to thebasement, three inches ofwater already covered theground, and the levelwasrising fast. I stood on thebottom step, thoughtsracing, wondering whatwas going on (hurricane?

nuclear attack?earthquake? tornado?alien invasion?)§ andtrying to figure out whattodo.Standing there in myboxer shorts, I becameconscious of thethunderous pounding ofmy heart. My mouth wasdry, my breathing wasquick, my muscles weretense, my heart was

racing, adrenaline wascoursing through mybloodstream—my fight-or-flight response was fullyactivated. As I felt myheartthudding,itoccurredto me that my physicalsensations were like thoseof a panic attack or anepisode of phobic terror.But even though thedanger now was so muchmore real than during a

panicattack,eventhoughIwasawarethatImightgethurtoreven(whoknows?)die as the roof caved inand giant trees tumbled, Iwas less unhappy than Iwould be during a panicattack. I was scared, yes,but I was marveling atNature’s force, her abilitytoteardownmyseeminglysolidhousearoundmeandto knock down scores of

big trees. It was actuallysortof…exciting.Apanicattackisworse.‖The next several weekswere spent dealing withinsurance claims anddisaster recoverytechniciansandrealestateagents and movers—andnot at all working on mybook.Asthepreciousdaysof my dwindling leavetickedaway,Iagainfound

myself in an excruciatingbind.IfIdidn’tgobacktowork, I feared, I wouldlose my job; if I did gobacktowork,I’dprobablymiss my book deadline(and maybe lose my jobanyway). Worse stillwouldbetofinallyreceivethe external confirmationofmy inner conviction allthese years: that I am afailure—weak, dependent,

anxious,shameful.“Scott!” Dr. W. saidwhen I was going on inthis fashion. “Are youlistening to yourself?You’vealreadywrittenonebook. You’re supporting afamily.Youhaveajob.”Later that day he e-mailedme:

As I was writing mynotes today after we

met, it occurred to methatyouneed tobetterinternalize positivefeedback.… Yourcapabilities are farfrom the picture ofinadequacy that youcarry around in yourhead. Please try andabsorb.

Iwroteback:

I’ll try to absorb thesecomments—but Iimmediately discountor back away orrationalizethem.

Heresponded:

Scott, the automaticresponse is to discountpositive feedback. Thatiswhy it is so difficultto change. But the

beginning of thatprocess is a pushbackagainst the negativejuggernaut.

Trying is all anyonecanask.

The irony, of course, isthat, as Dr. W. keepstelling me, the route tomentalhealthandfreedomfrom anxiety is to deepen

mysenseofwhathecalls,drawing on the work ofthe cognitive psychologistAlbert Bandura, self-efficacy.(Bandurabelievedthat repeatedly proving tooneself one’s competenceand ability to mastersituations,anddoingsoinspiteoffeelingsofanxiety,depression, orvulnerability, builds upself-confidence and

psychologicalstrengththatcan provide a bulwarkagainst anxiety anddepression.) Yet writingthis bookhas requiredmeto wallow in my shame,anxiety, and weakness sothatIcanproperlycaptureand convey them—anexperience that has onlyreinforced how deep andlong-standing my anxietyand vulnerability are. Of

course,Isupposethatevenas writing this book hasintensified my sense ofshame, anxiety, andweakness and hasaccentuated those feelingsof “helpless dependency”that, according to thepsychiatrists at McLeanHospital, did inmy great-grandfather, it has alsohelpedme appreciate thatmy efforts to withstand

their corrosive effectprovide some evidencethatIhavetheresourcestoovercomethem.Maybebytunneling into my anxietyfor this book I can alsotunnel out the other side.Not that I can escape myanxiety or be cured of it.But in finishing this book,albeitabookthatdwellsatgreat length on myhelplessness and

inefficacy, maybe I amdemonstrating a form ofefficacy, perseverance,productivity—and, yes,resilience.MaybeIamnot,forthatmatter—despite mydependency onmedication, despite myflirtations withinstitutionalization,despite the genotype ofpathologyhandeddownto

me by my ancestors,despite the vulnerabilityand what sometimes feelslike the unbearablephysical and emotionalagony of my anxiety—asweak as I think I am.Consider the openingsentence of this book: “Ihave an unfortunatetendency to falter atcrucial moments.” Thatstatementfeelstruetome.

(“The neurotic,” KarenHorney writes in TheNeurotic Personality of OurTime, “tenaciously insistsonbeingweak.”)Andyet,as Dr. W. is alwayspointing out, Idid survivemy wedding and havemanaged(sofar)toremainproductive and gainfullyemployed for more thantwentyyearsdespiteoftendebilitatinganxiety.

“Scott,” he says. “Overthe last few years, you’verunamagazineandeditedmany of its cover stories,worked on your book,taken care of your family,and coped with thedestruction of your houseand with the normalvicissitudesandchallengesof life.” I point out thatI’vemanaged all this onlywith the help of

(sometimes heavy)medication—and thatanything I’veaccomplished has beenaccompanied by constantworry and frequent panicand has been punctuatedby moments of near-complete breakdown thatleavemealwaysat riskofbeing exposed for theanxious weakling that Iam.

“Youhaveahandicap—anxietydisorder,”he says.“Yet youmanage it and, Iwould say, even thrivedespite it. I still think wecan cure you of it. But inthemeantime,youneedtorecognizethat,givenwhatyou’re up against, you’veaccomplished a lot. Youneedtogiveyourselfmorecredit.”Maybe finishing this

book and publishing it—and, yes, admitting myshame and fear to theworld—will beempowering and anxietyreducing.I suppose I’ll find out

soonenough.

* Recent research on sleep cyclessuggests that difficulty in risingearlyisnot(entirely)acharacter

failing but rather a biologicallyhardwired trait: some people’scircadian rhythms make themwhat researchers call “morningdoves,” leapingeasilyoutofbedin the morning and fading atnight, whereas other people are“night owls,” productivelyburning the midnight oil andunable to get out of bed in themorning.

† Actually, an intriguing body ofresearchhasfoundthatclinically

depressedpeopletendtobemoreaccurate in their self-assessmentsthan healthy people, suggestingthat an ample quotient of self-delusion—of thinking you’rebetter or more competent thanyouinfactare—isusefulforgoodmental health and professionalsuccess.

‡ As we saw in chapter 9, theresearch of Jerome Kagan, KerryRessler, and others suggests thatgenes play a large role in

determiningone’sinnatelevelsofnervousnessandresilience.

§ It was, my insurance companywouldlaterconclude,“atornadicevent.”

‖As if to confirm that, two nightslater I woke up with astomachache, which instantlytriggeredmiserablebody-quakingpanic that had me desperatelygulping vodka and Xanax andDramamine in headlong pursuitof unconsciousness—probably

putting myself at more risk ofdeath than the house-destroyingstormdid.

Acknowledgments

This bookmight not existif Kathryn Lewis had not,unbeknownst to me,shown an e-mail with myinchoatethoughtstoSarahChalfant of the WylieAgency—and it wouldalmost certainly not existif Sarah had not then

tracked me down andspurred me, patiently butrelentlessly, toproduceanactual proposal. ScottMoyers,duringhisstintattheWylieAgency,heldmyhand through some darktimes, providing bothwisdom and invaluablepractical advice. AndrewWylieisaslegendhashim:agreatandfearsomeagent—you want him on your

side. No one is a greaterchampion of writers thanAndrew.Marty Asher, a

sympathetic editor,immediately graspedwhatIwastryingtodo,andhisenthusiasm for the bookbrought it to Knopf.Marty’s warmth and hismanykindnessessustainedthebook(andme)throughsomedifficultstretches.

I owe Sonny Mehtatriply: first for signing offon Marty’s originalacquisition of the book;second for his patience asthe writing dragged on;andthirdforassigningthemanuscript to Dan Frankfor editing. Dan’sministrations made thisbook so much better. Ihave worked as an editorfor twenty years, so I like

to think I know goodediting when I encounterit:Danisabrillianteditorand a kind man. AmySchroederhelpeduntanglemy prose. Jill Verrillo,GabrielleBrooks,JonathanLazzara, and Betsy Sallee,among others, make it apleasure to be a Knopfauthor.I am grateful for

fellowships at the Yaddo

and MacDowell colonies,which gave me time andspacetowork.Lots of people

contributed ideas, steeredme to useful sources, orprovided support in otherways: Anne Connell,Meehan Crist, KathyCrutcher,TobyLester,Joyde Menil, Nancy Milford,Cullen Murphy, JustineRosenthal, Alex Starr, and

Graeme Wood. AlaneMason, Jill Kneerim, andPaul Elie all providedhelpful early feedback onthebookproposalbeforeitwas fully formed. AliesMuskin, executive directorat the Anxiety andDepression Association ofAmerica, was generouswith her time and herRolodex.My brother-in-law, Jake

Pueschel, providedvaluable researchassistance, tracking downhundreds of scholarlyarticles for me and, moreessentially, helped me toprocess and interpret mygenetic data. Jake’sparents, my mother- andfather-in-law Barbara andKris Pueschel, providedboth child care andmoralsupport—andtoleratedmy

too-frequentabsencesfromfamilyeventswhileIracedtomeetdeadlines.At The Atlantic, I am

gratefultocolleagues(andformer colleagues) whoendured my periodicabsences and filled in formewhile Iworkedon thebook, among them BobCohn, James Fallows,Geoff Gagnon, JamesGibney, Jeffrey Goldberg,

CorbyKummer,ChrisOrr,Don Peck, Ben Schwarz,Ellie Smith, and YvonneRolzhausen. (On thebusiness side, Atlanticpresident Scott Havens,Atlantic Media presidentJustin Smith, and AtlanticMedia chairman andowner David Bradleyshowed blessedforbearance in allowingme time to work on this

book.) More than anyother Atlantic colleagues,though, I owe JenniferBarnett,MariaStreshinsky,and James Bennet, whowereexceedinglygenerousin working around theproblems my absencescaused. Iworry I’ve takenyearsoffJames’slife.Despiteeverything,Iam

grateful to Dr. L., Dr. M.,Dr. Harvard, Dr. Stanford,

and various othertherapists and socialworkers and hypnotistsand pharmacologists whoare not named or got lefton the cutting room floor.I am unreservedly andongoingly grateful to Dr.W.: thank you for helpingkeepmeafloat.I want to thank my

family—especiallymydad,my mom, my sister, and

my grandfather. I lovethem all. None of them(with the qualifiedexception of my father)were happy I was writingthis book—and they wereall even unhappier to beincluded in it themselves.(Iamespeciallygratefultomy father for sharing hisdiary with me.) I havetriedtobeasaccurateandobjective as my memory

and the limiteddocumentary recordpermit. Some familymembers would disputeaspects of what I havewritten here. I worry thatsome in my family viewmy revelations aboutChester Hanford as adesecrationofhismemoryand a posthumousdespoiling of his dignity.For what it’s worth, I

respect him tremendously,andIhopethatinmyownanxious struggle I can liveup to the standards ofgrace, decency, kindness,and perseverance heembodied. (I owe specialthanks to my grandfather,who—though he madeclear he didn’t want toknow what was in hisfather’spsychiatricrecords—was willing to let me

find out and helped menavigate probate court tosecurethem.)As ever, my deepest

thanks go to my wife,Susanna. Early on, shelogged many hours at theNational Institutes ofHealth Library, trackingdown scientific articlesand books. She also wentfarbeyondanyreasonableexpectation of spousal

support in helping mefightthroughlegalthicketsand bureaucraticimpediments to gainaccesstothementalhealthrecords of my great-grandfather. Mostimportant, if you’ve readthis book, you know thatholding me together cansometimes be challenging,unrewarding work. Thatworkfallsmostheavilyon

Susanna—and for that Iowe her more than I caneverrepay.

Notes

CHAPTER1:THENATUREOFANXIETY

1 accounting for 31percent of theexpenditures:Figureonanxiety and mentalhealth careexpenditures comesfrom “The EconomicBurdens of AnxietyDisorders in the1990s,” a

comprehensive reportpublished in TheJournal of ClinicalPsychiatry 60, no. 7(July1999).

2 “lifetime incidence”ofanxiety disorder:Ronald Kessler, anepidemiologist atHarvard, has spentdecades studying this.See, for instance, his

paper “LifetimePrevalence and Age-of-Onset Distributions ofDSM-IV Disorders inthe NationalComorbidity SurveyReplication,” Archivesof General Psychiatry62, no. 6 (June 2005):593–602.

3Astudypublished:R.C.Kessler et al.,

“PrevalenceandEffectsof Mood Disorders onWorkPerformanceinaNationallyRepresentative Sampleof U.S. Workers,” TheAmerican Journal ofPsychiatry 163 (2006):1561–68. See also“EconomicBurdens.”

4 themediannumberofdays: U.S. Bureau of

Labor Statistics, “TableR67: Number andPercent Distribution ofNonfatal OccupationalInjuries and IllnessesInvolving Days Awayfrom Work by Natureof Injuryor IllnessandNumber of Days AwayfromWork,2001.”

5 Americans filled fifty-three million

prescriptions: DrugTopics,March2006.

6 Xanax prescriptionsjumped 9 percentnationally: “Taking theWorry Cure,”Newsweek,February24,2003. See also Restak,Poe’sHeart,185.

7 the economic crashcaused prescriptions:Report from Wolters

Kluwer Health, amedical informationcompany, cited inRestak, Poe’s Heart,185.

8 A report published in2009: Mental HealthFoundation, In theFaceof Fear, April 2009, 3–5.

9 A recent paper:“Prevalence, Severity,

and Unmet Need forTreatment of MentalDisorders in theWorldHealth OrganizationWorld Mental HealthSurveys,”TheJournalofthe American MedicalAssociation 291 (June2004):2581–90.

10Acomprehensiveglobalreview: “Prevalenceand Incidence Studies

ofAnxietyDisorders:ASystematic Review ofthe Literature,” TheCanadian Journal ofPsychiatry 51 (2006):100–13.

11 other studies havereported similarfindings: For instance,“Global Prevalence ofAnxiety Disorders: ASystematic Review and

Meta-regression,”Psychological Medicine10(July2012):1–14.

12Primarycarephysiciansreport: See, forinstance, “Content ofFamilyPractice:ADataBank for Patient Care,Curriculum, andResearch in FamilyPractice—526,196Patient Problems,” The

Journal of FamilyPractice 3 (1976): 25–68.

13 One large-scale studyfrom 1985: “TheHidden Mental HealthNetwork: Treatment ofMental Illness by Non-psychiatricPhysicians,”Archives of GeneralPsychiatry 42 (1985):89–94.

14 one in three patientscomplained: “PanicDisorder: EpidemiologyandPrimaryCare,”TheJournal of FamilyPractice 23 (1986):233–39.

15 20 percent of primarycare patients: “QualityofCareofPsychotropicDrug Use in InternalMedicine Group

Practices,” WesternJournal of Medicine 14(1986):710–14.

16 “Woody Allen gene”:See, for instance, PeterD. Kramer, “Tappingthe Mood Gene,” TheNew York Times, July26, 2003. See alsoRestak, Poe’s Heart,204–12.

17 “The real excitement

here”: Thomas Insel,“Heeding Anxiety’sCall” (lecture,May 19,2005).

18 “as vain as a child’sstory”: Roccatagliata,History of AncientPsychiatry,38.

19 “if one’s body andmind”: MauriceCharlton, “PsychiatryandAncientMedicine,”

inHistorical Derivationsof Modern Psychiatry,16.

20 “All that philosophershave written”:Charlton, “PsychiatryandAncientMedicine,”12.

21 One study found thatchildren: See, forinstance, RachelYehuda et al., “Trans-

generational Effects ofPosttraumatic StressDisorder in Babies ofMothersExposedtotheWorld Trade CenterAttacks DuringPregnancy,” TheJournal of ClinicalEndocrinology andMetabolism 90, no. 7(July 2005): 4115Rachel Yehuda et al.,“Gene Expression

Patterns Associatedwith PosttraumaticStress DisorderFollowing Exposure totheWorldTradeCenterAttacks,” BiologicalPsychiatry 66(7)(2009):708–11.

22 “Myself and fear wereborn twins”:Quoted inHunt, Story ofPsychology,72.

23 There’s also evidencethat: See, for instance,“The RelationshipBetween Intelligenceand Anxiety: AnAssociation withSubcortical WhiteMatter Metabolism,”Frontiers inEvolutionaryNeuroscience 3, no. 8(February 2012). (Alsoon high Jewish IQ:Steven Pinker, who in

2007 gave a lecturecalled “Jews, Genes,and Intelligence,” says“their average IQ hasbeen measured at 108to 115.”Richard Lynn,author of the 2004article “TheIntelligence ofAmerican Jews,” saysJewish intelligence ishalf a standarddeviation higher than

the European average.Henry Harpending,Jason Hardy, andGregory Cochran,University of Utahauthors of the 2005research report“Natural History ofAshkenaziIntelligence,” state thattheir subjects “score.75 to 1.0 standarddeviations above the

general Europeanaverage, correspondingtoanIQof112–115.”)

24 An influential study:“The Relation ofStrengthofStimulus toRapidity of Habit-Formation,” TheJournal of ComparativeNeurology andPsychology 18 (1908):459–82.

25 “We then face theprospect”: Los AngelesExaminer,November 4,1957, quoted in Tone,AgeofAnxiety,87.

26 “Van Gogh, IsaacNewton”: Los AngelesExaminer, March 23,1958, quoted in Tone,AgeofAnxiety,87.

27 “Withoutanxiety, littlewould be

accomplished”: Barlow,Anxiety and ItsDisorders,9.

28“Iawokemorningaftermorning”: James,Varieties of ReligiousExperience,134.

29 Petraeus … “rarelyfeels stress at all”:Steve Coll, “TheGeneral’s Dilemma,”The New Yorker,

September8,2008.

CHAPTER2:WHATDOWETALKABOUTWHENWETALKABOUT

ANXIETY?

1 “usually linkedwithastrong”: Jaspers,GeneralPsychopathology, 113–14.

2“asenseofforeboding”:Lifton, Protean Self,101.

3 “the internalprecondition of sin”:Niebuhr, Nature andDestiny,vol.1,182.

4 “the most pervasivepsychologicalphenomenon”: HochandZubin,Anxiety,v.

5 “The mentalistic andmulti-referenced term”:Theodore R. Sarbin,“Anxiety:Reificationof

a Metaphor,” ArchivesofGeneralPsychiatry10(1964):630–38.

6 “to feelings”: Kagan,WhatIsEmotion?,41.

7 “as wine to vinegar”:See, for instance,“Three Essays on theTheoryofSexuality,”inFreud,BasicWritings.

8 “with a manualstimulation”:Quotedin

Roccatagliatia, Historyof Ancient Psychiatry,204.

9 “It is almostdisgraceful”: Freud,ProblemofAnxiety,60.

10 “When a mother isafraid”: Horney,NeuroticPersonality,41.

11 Studies of the:DSM-II:See, for instance, R.SpitzerandJ.Fleiss,“A

Re-analysis of theReliability ofPsychiatric Diagnosis,”The British Journal ofPsychiatry 125 (1974):341–47; Stuart A. Kirkand Herb Kutchins,“The Myth of theReliability of DSM,”Journal of Mind andBehavior 15, nos. 1–2(1994):71–86.

12 “stress tradition”: Formore on the stresstradition, see thesection “Anxiety andtheStressTradition”inHorwitzandWakefield,All We Have to Fear,200–4.

13“asister,fidusAchates”:Burton,Anatomy,261.

14 “are affrighted still”:Ibid.,431.

15 “Don’t allow the sumtotal”: Breggin,Medication Madness,331.

16 Moreover, thebrainofa research subject:Kagan, What IsEmotion?,83.

17 humans whoseamygdalae getdamaged: See, forinstance,“Fearand the

Amygdala,”TheJournalof Neuroscience 15, no.9 (September 1995):5879–91.

18 “the final and mostexciting contest”:Cannon, BodilyChanges,74.

19 “The progress frombrute to man”: James,Principles of Psychology,415.

20 “One day”: Quoted inFisher, House of Wits,81.

21 “Contrary to the viewof some humanists”:LeDoux, EmotionalBrain,107.

22EvenAplysiacalifornica:This comes from theresearchofEricKandel,which is described inBarber, Comfortably

Numb,191–96.23 “It is not obvious”:Kagan, What IsEmotion?,17.

24 “entering a seeminglyinvoluntary state”:Barlow,Anxiety and ItsDisorders,35.

25 “How many hipposworry”: Sapolsky,Zebras,182.

26 “A rat can’t worry”:

Quoted in StephenHall, “Fear Itself,” TheNew York TimesMagazine, February 28,1999.

27 “Theta activity is arhythmic burst”: Grayand McNaughton,Neuropsychology ofAnxiety,12.

28“ThisremarkofPlato”:Maurice Charlton,

“Psychiatry andAncient Medicine,” inGaldston, HistoricDerivations,15.

29 Meditation led todecreased density: G.Desbordes et al.,“Effects of Mindful-Attention andCompassionMeditationTraining on AmygdalaResponse to Emotional

Stimuli inanOrdinary,Non-meditative State,”Frontiers of HumanNeuroscience 6 (2012):292.

30 Other studies havefound that Buddhistmonks: See, forinstance, Richard J.Davidson and AntoineLutz, “Buddha’s Brain:Neuroplasticity and

Meditation,” IEEESignal ProcessingMagazine 25, no. 1(January 2008): 174–76.

31 suppress their startleresponse: See, forinstance, R. W.Levenson, P. Ekman,and M. Ricard,“Meditation and theStartle Response: A

Case Study,” Emotion12, no. 3 (June 2012):650–58; for additionalcontext, see TomBartlett, “The Monkand the Gunshot,” TheChronicle of HigherEducation, August 21,2012.

32evenold-fashionedtalktherapy: Richard A.Friedman, “Like Drugs,

Talk Therapy CanChange BrainChemistry,” The NewYork Times, August 27,2002.

33 “My theory”: WilliamJames first articulatedthis in “What Is anEmotion?,” an articlehepublishedinMind,aphilosophy journal, in1884.

34 When researchers atColumbia: S. Schachterand J. E. Singer,“Cognitive, Social, andPhysiologicalDeterminants ofEmotional State,”PsychologicalReview69,no. 5 (1962): 379–99.Joseph LeDoux has agooddescriptionofthisexperi-ment,andofthehistory of the James-

Lange theory, inEmotionalBrain,46–49.

35 “fear of death,conscience, guilt”:Tillich, “ExistentialPhilosophy,” Journal ofthe History of Ideas 5,no. 1 (1944): 44–70.(This later appeared inTillich’s 1959 bookTheologyofCulture.)

36themomentananxious

patient: See, forinstance, Gabbard, “ANeurobiologicallyInformed PerspectiveonPsychotherapy,”TheBritish Journal ofPsychiatry 177 (2000):11;A.ÖhmanandJ.J.F.Soares,“UnconsciousAnxiety: PhobicResponses to MaskedStimuli,” Journal ofAbnormal Psychology

(1994); John T.Cacioppo et al., “ThePsychophysiology ofEmotion,”Handbook ofEmotions 2 (2000):173–91.

37 Richard Burton couldnot bear: Shawn,Wish,10.

38 how to eliminate fearresponses in cats:Joseph Wolpe,

Psychotherapy byReciprocal Inhibition(Stanford, Calif.:Stanford UniversityPress,1958),53–62.

39 “chimney sweeping”:Breger,Dream,29.

CHAPTER3:ARUMBLINGINTHEBELLY

1 “scare the hell out ofthe patient”: DavidBarlow “ProvidingBestTreatments forPatientswith Panic Disorder,”AnxietyandDepressionAssociation ofAmerican AnnualConference, Miami,March24,2006.

2 phobiacurerateofupto 85 percent: LaurenSlater, “The CruelestCure,” The New YorkTimes, November 2,2003.

3 Barlow himself has aphobia:“APhobiaFix,”The Boston Globe,November26,2006.

4 “It’s from1979”: J.K.Ritow, “Brief

Treatment of aVomiting Phobia,”American Journal ofClinical Hypnosis 21,no.4(1979):293–96.

5 “a phobia and a beef-steak”: Northfield,ConquestofNerves,37.

6asmanyas12percent:Harvard MedicalSchool, Sensitive Gut,71.

7Firstidentifiedin1830:Ibid.,72.

8 Inonewell-knownsetof experiments:William E. Whiteheadet al., “Tolerance forRectosigmoidDistention in IrritableBowel Syndrome,”Gastroenterology98,no.5 (1990): 1187;William E. Whitehead,

Bernard T. Engel, andMarvin M. Schuster,“Irritable BowelSyndrome,” DigestiveDiseases and Sciences25, no. 6 (1980): 404–13.

9 an article in themedical journal Gut:Ingvard Wilhelmsen.“Brain-Gut Axis as anExample of the Bio-

psycho-social Model,”Gut47,supp.4(2000):5–7.

10 “nervous in origin”:Walter Cannon, “TheInfluence of EmotionalStatesontheFunctionsof the AlimentaryCanal,” The AmericanJournal of the MedicalSciences 137, no. 4(April1909):480–86.

11 between 42 and 61percent: AndrewFullwood and DouglasA. Drossman, “TheRelationship ofPsychiatric Illness withGastrointestinalDisease,”AnnualReviewof Medicine 46, no. 1(1995):483–96.

12 40 percent overlapbetween patients:

Robert G. Maunder,“Panic DisorderAssociated withGastrointestinalDisease: Review andHypotheses,”JournalofPsychosomatic Research44,no.1(1998):91.

13 “Fear brings aboutdiarrhea”: Quoted inRoccatagliata, Historyof Ancient Psychiatry,

106.14 “People attacked byfear”: Quoted inSarason andSpielberger, Stress andAnxiety,vol.2,12.

15 “90 percent redness”:WolfandWolff,HumanGastricFunction,112.

16 One of the morealarming: Richard W.Seim, C. Richard

Spates, and Amy E.Naugle, “Treatment ofSpasmodic Vomitingand LowerGastrointestinalDistress Related toTravel Anxiety,” TheCognitive BehaviourTherapist 4, no. 1(2011):30–37.

17 weepingat a sadplay:Alvarez, Nervousness,

123.18 The nervousness andhypersensitivity: Ibid.,266.

19“Thestomachspecialisthastobe”:Ibid.,11.

20 “day and night for aweek”:Ibid.,22.

21 “a tense, high-pressuretypeofsalesmanager”:Ibid.,17.

22 “the cruelest prank ofnature”:Ibid.

23 A study published in:Angela L. Davidson,Christopher Boyle, andFraser Lauchlan,“Scared to LoseControl? General andHealthLocusofControlin Females with aPhobia of Vomiting,”Journal of Clinical

Psychology 64, no. 1(2008):30–39.

24AstheBritishphysicianandphilosopher:Tallis,Kingdom of InfiniteSpace,193.

25“Age56–57”:QuotedinDesmond and Moore,Darwin,531.

26“DiaryofHealth”:CitedatlengthinColp,ToBeanInvalid,43–53.

27 “knocked up”:Desmond and Moore,Darwin,530.

28 “We liked Dr.Chapman”: Quoted inColp,To Be an Invalid,84.

29“Whatthedevilisthis”:Hooker,LifeandLettersof Joseph DaltonHooker,vol.2,72.

30 “Darwin’s Illness

Revealed”: Anthony K.Campbell andStephanieB.Matthews,“Darwin’s IllnessRevealed,”PostgraduateMedicalJournal 81, no.954(2005):248–51.

31 “bad headache”:Bowlby, CharlesDarwin,229.

32 “Charles Darwin andPanic Disorder”:

ThomasJ.BarloonandRussell Noyes Jr.,“Charles Darwin andPanic Disorder,” TheJournal of theAmericanMedicalAssociation277,no.2(1997):138–41.

33 “neurotic hands”:Edward J. Kempf,“Charles Darwin—theAffectiveSourcesofHisInspirationandAnxiety

Neurosis,” ThePsychoanalyticReview 5(1918):151–92.

34 one pseudoscholarlypaper: Jerry Bergman,“Was Charles DarwinPsychotic? A Study ofHis Mental Health”(Institute of CreationResearch,2010).

35 “the most miserablewhich I ever spent”:

Darwin, Autobiography,28. 92 “I was out ofspirits”:Ibid.,28.

36 “I dread goinganywhere”: Life andLetters of CharlesDarwin,vol.1,349.

37 “I have therefore beencompelled”: Darwin,Autobiography,39.

38 He installed a mirror:Quammen, Reluctant

Mr.Darwin,62.39 In addition to Dr.Chapman’s icetreatment: SourcesincludeBowlby,CharlesDarwin; Colp,ToBe anInvalid; Desmond andMoore, Darwin;Browne, The Power ofPlace; and Quammen,The Reluctant Mr.Darwin;amongothers.

40 “a very bad form ofvomiting”: Bowlby,CharlesDarwin,300.

41 “I have been bad”:Ibid.,335.

42“Ihavebeenverybad”:Ibid.,343.

43“strivetosuppresstheirfeelings”:Ibid.,11.

44“Imusttellyou”:Ibid.,375.

45 “Without you, when Ifeel sick”: Desmondand Moore, Darwin,358.

46“OMammyIdolong”:Bowlby, CharlesDarwin,282.

CHAPTER4:PERFORMANCEANXIETY

1 Startingwhen hewasthirty: Oppenheim,“ShatteredNerves,”114.

2 “To that”: Davenport-Hines, Pursuit ofOblivion,56.

3 “mystifying andscandalously suddenretirement”: Quoted in

Marshall,SocialPhobia,140.

4 “They … to whom apublic examination”:“Memoir of WilliamCowper,” Procedings ofthe AmericanPhilosophicalSociety97,no.4(1953):359–82.

5“Myheadwasreeling”:Gandhi, Autobiography.(I was pointed to this

source by chapter 5 ofTaylorClark’sNerve.)

6“ThomasJefferson,too,had his law careerdisrupted”: AllJeffersonmaterial hereis drawn from JoshuaKendall’s AmericanObsessives,21.

7 a career-ending panicattack: Mohr, GaspingforAirtime,134.

8 “I had all these panicattacks”: “Hugh Grant:Behind That SmileLurks aDeadly SeriousFilmStar,”USAToday,December17,2009.

9 Elfriede Jelinek, theAustrian novelist: “AGloom of Her Own,”The New York TimesMagazine, November21,2004.

10 Sigmund Freud tookcocaine to medicate:See, for instance,Kramer,Freud,42.

11 The first case study oferythrophobia: Casper,Johann Ludwig,“Biographie d’une idéefixe” (translated intoFrench,1902),ArchivesdeNeurologie, 13, 270–287.

12“Itisnotasimpleact”:Darwin, Expression,284.

13 “the soul might havesovereign power”:Burgess, Physiology orMechanism of Blushing,49.

14 Writing in 1901, PaulHartenberg:Hartenberg, Les timideset la timidité (Félix

Alcon,1901).15 The term “socialphobia” first appeared:Pierre Janet, Lesobsessions et lapsychiatrie (Alcan,1903).

16 “the socially promotedshow of shame”: Ken-Ichiro Okano, “Shameand Social Phobia: ATranscultural

Viewpoint,” Bulletin oftheMenningerClinic58,no.3(1994):323–38.

17 In 1985, Liebowitzpublished an article:Michael Liebowitz etal., “Social Phobia,”Archives of GeneralPsychiatry 42, no. 7(1985):729–36.

18 As recently as 1994:“Disorders Made to

Order,” Mother Jones,July/August2002.

19 One study has found:See Manjula et al.,“Social AnxietyDisorder (SocialPhobia)—a Review,”International Journal ofPharmacology andToxicology 2, no. 2(2012):55–59.

20 Studies at the

University ofWisconsin: SeeDavidsonetal., “Whilea Phobic Waits:Regional BrainElectrical andAutonomic Activity inSocial Phobias DuringAnticipation of PublicSpeaking,” BiologicalPsychiatry 47 (2000):85–95.

21 “When I see anyoneanxious”: “OnAnxiety,” in Epictetus,Discourses,ch.13.

22 Kathryn Zerbe, apsychiatrist: See, forinstance, Kathryn J.Zerbe, “UnchartedWaters:PsychodynamicConsiderations in theDiagnosis andTreatment of Social

Phobia,” Bulletin of theMenningerClinic58,no.2 (1994): A3. See alsoCapps, Social Phobia,120–25.

23“Highlyanxiouspeopleread facialexpressions”: “AnxiousAdults Judge FacialCues Faster, but LessAccurately,” ScienceNews,July19,2006.

24 “this barometer cancause them”:“Whaddya Mean byThat Look?,” LosAngeles Times, July 24,2006.

25ArneÖhman,aSwedishneuroscientist: See, forinstance, Arne Öhman,“Face the Beast andFear the Face: Animaland Social Fears as

Prototypes forEvolutionary Analysesof Emotion,”Psychophysiology 23,no. 2 (March 1986):123–45.

26 “doing somethingfoolish”: Marshall,SocialPhobia,50.

27 ANational Institute ofMentalHealthstudy:K.Blair et al., The

American Journal ofPsychiatry 165, no. 9(September 2008):193–202;K.Blairetal.,Archives of GeneralPsychiatry 65, no. 10(October 2008): 1176–84.

28 “Generalized-social-phobia-relateddysfunction”: K. Blairetal.,“NeuralResponse

to Self- and OtherReferential Praise andCriticism inGeneralized SocialPhobia,” Archives ofGeneral Psychiatry 65,no.10 (October2008):1176–84.

29 they are notconsciously aware ofseeing: For instance,Murray B. Stein et al.,

“Increased AmygdalaActivation to Angryand ContemptuousFaces in GeneralizedSocialPhobia,”Archivesof General Psychiatry59, no. 11 (2002):1027.

30 “Unconsciouslyperceived signals ofthreat”: Zinbarg et al.,“NeuralandBehavioral

Evidence for AffectivePriming fromUnconsciouslyPerceived EmotionalFacial Expressions andthe Influence of TraitAnxiety,” Journal ofCognitive Neuroscience20, no. 1 (January2008):95–107.

31 Murray Stein, apsychiatrist: Murray B.

Stein, “NeurobiologicalPerspectives on SocialPhobia: FromAffiliation to Zoology,”BiologicalPsychiatry44,no.12(1998):1277.

32thesocialhierarchiesofparticular baboonpopulations: See, forinstance, RobertSapolsky, “TesticularFunction, Social Rank

andPersonalityAmongWild Baboons,”Psychoneuroendocrinology16, no. 4 (1991): 281–93; Robert Sapolsky,“The Endocrine Stress-Response and SocialStatus in the WildBaboon,”HormonesandBehavior 16, no. 3(September 1982):279–92; RobertSapolsky, “Stress-

Induced Elevation ofTestosteroneConcentrations in HighRanking Baboons: Roleof Catecholamines,”Endocrinology118no.4(April1986):1630.

33 the happiest-seemingand least stressedmonkeys: Gesquiere etal., “Life at the Top:RankandStressinWild

Male Baboons,”Science333, no. 6040 (July2011):357–60.

34 monkeys withenhanced serotonergicfunction: See, forinstance,Raleighetal.,“SerotonergicMechanisms PromoteDominance Acquisitionin Adult Male VervetMonkeys,” Brain

Research 559, no. 2(1991):181–90.

35 altered serotoninfunction in certainbrain regions: Forinstance, Lanzenbergeret al., “ReducedSerotonin-1A ReceptorBinding in SocialAnxiety Disorder,”BiologicalPsychiatry61,no. 9 (May 2007):

1081–89.36 Prozac and Paxil canbe: See, for instance,van der Linden et al.,“The Efficacy of theSelective SerotoninReuptake Inhibitors forSocialAnxietyDisorder(Social Phobia): AMeta-analysis ofRandomizedControlledTrials,” International

ClinicalPsychopharmacology 15,supp. 2 (2000): S15–23; Stein et al.,“Serotonin TransporterGene PromoterPolymorphism PredictsSSRI Response inGeneralized SocialAnxiety Disorder,”Psychopharmacology187,no.1(July2006):68–72.

37 when nonanxious,nondepressed peopletake SSRIs: See, forinstance, Wai S. Tseand Alyson J. Bond,“SerotonergicIntervention AffectsBoth SocialDominanceand AffiliativeBehaviour,”Psychopharmacology,161(2002):324-330

38 the monkeys that risethe highest: See, forinstance,Morganetal.,“Social Dominance inMonkeys:DopamineD2Receptors and CocaineSelf-Administration,”Nature Neuroscience 5(2002): 169–74;Morgan et al.,“Predictors of SocialStatus in CynomolgusMonkeys (Macaca

fascicularis) AfterGroup Formation,”American Journal ofPrimatology 52, no. 3(November 2118):115–31.

39 people diagnosedwithsocial anxiety disorder:See, for instance, Steinand Stein, “SocialAnxiety Disorder,”Lancet 371 (2008):

1115–25.40 One 2008 study foundthat half: ArthurKummer, FranciscoCardoso, and AntonioL.Teixeira, “Frequencyof Social Phobia andPsychometricProperties of theLiebowitz SocialAnxiety Scale inParkinson’s Disease,”

Movement Disorders 23,no. 12 (2008): 1739–43.

41 Multiple recent studieshave found: See, forinstance, Schneier etal.,“LowDopamineD2Reception BindingPotential in SocialPhobia,” The AmericanJournal of Psychiatry157(2000):457–59.

42 Murray Stein, amongothers: Stein, MurrayB., “NeurobiologicalPerspectives on SocialPhobia:fromAffiliationto Zoology,” BiologicalPsychiatry 44, no. 12(1998): 1277–85. Seealso David H. Skuseand Louise Gallagher,“Dopaminergic-NeuropeptideInteractions in the

SocialBrain,”Trends inCognitive Sciences 13,no.1(2009):27–35.

43 where you fall on thespectrum: See, forinstance, Seth J.Gillihan et al.,“Association BetweenSerotonin TransporterGenotype andExtraversion,”Psychiatric Genetics 17,

no.6(2007):351–54.44 But Robert Sapolskyhas found: Sapolsky,“Social Status andHealth in Humans andOtherAnimals,”AnnualReview of Anthropology33(2004):393–418.

45 In the late1990s,DirkHellhammer: DirkHelmut Hellhammer etal., “Social Hierarchy

and AdrenocorticalStress Reactivity inMen,”Psychoneuroendocrinology22, no. 8 (1997): 643–50.

46 In 1908, twopsychologists: RobertM.Yerkes and JohnD.Dodson, “The RelationofStrengthofStimulusto Rapidity of Habit-

Formation,” TheJournal of ComparativeNeurology andPsychology 18, no. 5(1908):459–82.

47Bertoia…“couldn’thitandsometimesbobbledfielding plays”: Tone,The Age of Anxiety,113–14.

48“likeasongthatgotinmy head”: Quoted in

Ballard,BeautifulGame,76.

49 “disreturnophobia”:“Strikeouts and Psych-Outs,” The New YorkTimesMagazine,July7,1991.

50Theexplicitmonitoringtheoryofchoking:SianL. Beilock and ThomasH. Carr, “On theFragility of Skilled

Performance: WhatGovernsChokingUnderPressure?,” Journal ofExperimentalPsychology: General130,no.4(2001):701.

51 Beilock has found thatshe can: For more onthis,seeBeilock,Choke.

52aneural“trafficjam”ofworry:QuotedinClark,Nerve,208.

53 “foundhimself in suchdisgrace”: Herodotus,Histories,vol.4,bk.7.

54 inure their soldiers toanxiety: Gabriel, NoMoreHeroes,104.

55 and also valerian, amildtranquilizer: Ibid.,139.

56 Researchers at JohnsHopkins University:“Stress Detector for

Soldiers,” BBC WorldNews,May29,2002.

57 The Anglo-SaxonChronicle recounts:Cited in Gabriel, NoMoreHeroes,51.

58 “at best aconstitutionallyinferiorhuman being”:Herman, Trauma andRecovery,21.

59 A 1914 article: “The

Psychology of Panic inWar,” American ReviewofReviews 50 (October1914):629.

60 “hyperconsiderateprofessional attitude”:Quoted in Barber,ComfortablyNumb,73.

61 “because only such ameasure wouldprevent”: Quoted inBourke,Fear,219.

62“Itisnowtimethatourcountry”:Ibid.

63 General George Pattonof the U.S. Armydenied: Shephard,WarofNerves,219.

64 dishonorablydischarged forcowardice: JeffreyGettleman, “ReducedCharges for SoldierAccused of Cowardice

in Iraq,”TheNewYorkTimes, November 7,2003.

65 the first person to beformally diagnosed:Jacob Mendes DaCosta, “On IrritableHeart:AClinical StudyofaFormofFunctionalCardiac Disorder andIts Consequences,” TheAmerican Journal of the

Medical Sciences 121,no.1(1871):2–52.

66 Studies of “self-soilingrates”:Collins,Violence,46.

67 A survey of one U.S.combat division: PaulFussell,“TheRealWar,1939–45,”TheAtlantic,August1989.

68 Another survey ofWorld War II

infantrymen: Kaufman,“ ‘Ill Health’ as anExpression of Anxietyin a Combat Unit,”Psychosomatic Medicine9(March1947):108.

69 “Hell … all thatproves”: Quoted inClark,Nerve,234.

70 “I could feel atwitching”:Manchester, Goodbye,

Darkness,5.71“Now,thosewhofailtoregister”: ChristopherHitchens, “The BlairHitch Project,” VanityFair,February2011.

72 needed a man “withiron nerve”: Alvarez,Nervousness,18.

73 Comprehensive studiesconducted duringWorld War II: See, for

instance, Grinker andSpiegel, Men UnderStress.

74 “These people will beable to collect”: Leach,SurvivalPsychology,24.

75 “uncontrolledweeping”:Ibid.,25.

76 civilians withpreexisting neuroticdisorders: Janis, AirWar,80.

77 “Neurotics turned outto be”: Bourke, Fear,231.

78 “looking asworried asthey have felt”: FelixBrown, “CivilianPsychiatric Air-RaidCasualties,” The Lancet237, no. 6144 (May1941):689.

79 One fascinating studyof stress: V. A. Kral,

“PsychiatricObservations UnderSevere Chronic Stress,”TheAmericanJournalofPsychiatry 108 (1951):185–92.

80“unprecedentedinover30 years”: Kathleen E.Bachynski et al.,“Mental Health RiskFactors for Suicides intheUSArmy,2007–8,”

InjuryPrevention18,no.6(2012):405–12.

81 more than 10 percentof Afghanistanveterans: Hoge et al.,“Mental HealthProblems, Use ofMentalHealthServices,and Attrition fromMilitary Service AfterReturning fromDeployment to Iraq or

Afghanistan,” JAMA259, no. 9 (2006):1023–32.

82 army veteransdiagnosed with post-traumatic stressdisorder: Boscarino,Joseph,“Post-traumaticStress Disorder andMortality Among U.S.Army Veterans 30Years After Military

Service,” Annals ofEpidemiology 16, no. 4(2006):248–56.

83thesuicideratereacheda ten-year high: “MikeMullen on MilitaryVeteran Suicide,”HuffingtonPost,July2,2012.

84 “were some of thegreatest”: Charles A.Morgan et al.,

“Relationship AmongPlasma Cortisol,Catecholamines,Neuropeptide Y, andHuman PerformanceDuring Exposure toUncontrollable Stress,”Psychosomatic Medicine63, no. 3 (2001): 412–22.

85 Some individuals withhigh NPY: “Intranasal

Neuropeptide Y MayOffer TherapeuticPotential for Post-traumatic StressDisorder,” MedicalPress,April23,2013.

86 AdministeringNPYviaa nasal spray: CharlesA. Morgan III et al.,“Trauma ExposureRather ThanPosttraumatic Stress

Disorder Is Associatedwith Reduced BaselinePlasma Neuropeptide-YLevels,” BiologicalPsychiatry 54, no. 10(2003):1087–91.

87 Researchers at theUniversityofMichigan:Brian J. Mickey et al.,“Emotion Processing,Major Depression, andFunctional Genetic

Variation ofNeuropeptide Y,”Archives of GeneralPsychiatry 68, no. 2(2011):158.

88 with moreglucocorticoidreceptors: Mirjam vanZuiden et al., “Pre-existing HighGlucocorticoidReceptor Number

PredictingDevelopment ofPosttraumatic StressSymptoms AfterMilitary Deployment,”TheAmericanJournalofPsychiatry 168, no. 1(2011):89–96.

89 “[Russell] used tothrowupall thetime”:George Plimpton,“SportsmanoftheYear

Bill Russell,” SportsIllustrated, December23,1968.

90 he ordered that thepregamewarm-up:See,for instance, JohnTaylor,TheRivalry:BillRussell, WiltChamberlain, and theGoldenAgeofBasketball(New York: RandomHouse,2005).

91 “one of the greatmysteriesinthehistoryof sport”: “LitoSheppard SaysDonovan McNabbThrewUp in theSuperBowl,” CBSPhilly, July8,2013.

92 “You must wonderwhat makes a man”:Gay Talese, “TheLoser,” Esquire, March

1964.93 Hoping to conquer hisanxiety:ThissectiononPisa in wartime isdrawn from Arieti,Parnas.

CHAPTER5:“ASACKOFENZYMES”

1 Reportedly, it did:“Restless Gorillas,”Boston Globe,September 28, 2003;“Restless and Caged,Gorillas SeekFreedom,” BostonGlobe, September 29,2003.

2 “In my last serious

depression”:Quotedin,among many otherplaces, Kramer, Freud,33. For more onFreud’s use of cocaine,see Markel, AnAnatomyofAddiction.

3 “I take very smalldoses”: Davenport-Hines, Pursuit ofOblivion,154.

4Itisanironyofmedical

history: This irony hasbeen noted by PeterKramer,amongothers.

5 they were ingestingalcohol: Tone, Age ofAnxiety,10.

6 “a suitable form ofalcohol”: Quoted inShorter, Before Prozac,15.

7The1899editionofTheMerck Manual: Tone,

AgeofAnxiety,10.8 “quick-curenostrums”:Topics of the Times,The New York Times,January23,1906.

9 TheMerckManualwasstill recommending:Tone, Age of Anxiety,22.

10 “more of a menace tosociety”: Quoted inTone, Age of Anxiety,

25.11ButwhenFrankBerger:Much of the history ofFrank Berger andMiltown in thesepagesdraws heavily fromAndrea Tone’s Age ofAnxiety, EdwardShorter’sBefore Prozac,and Mickey Smith’sSmallComfort.

12 “The mold is as

temperamental”:QuotedinTone,Age ofAnxiety,34.

13 “The compound had aquieting effect”: TaylorManor Hospital,Discoveries in BiologicalPsychiatry,122.

14 “Wehad about twentyRhesus”: Quoted inTone, Age of Anxiety,43.

15 “individuals who arepleasantly”: Henry H.Dixon et al., “ClinicalObservations onTolserol in HandlingAnxiety TensionStates,” The AmericanJournal of the MedicalSciences 220, no. 1(1950):23–29.

16 The New Jerseypsychiatrist reported

back:Borrus,“StudyofEffect of Miltown (2-Methyl-2-n-Propyl-1,3-PropoanediolDicarbamate) onPsychiatricStates,”TheJournal of theAmericanMedical Association,April 30, 1955, 1596–98.

17 The psychiatrist inFlorida: Lowell Selling,

“ClinicalUse of aNewTranquilizing Drug,”The Journal of theAmerican MedicalAssociation, April 30,1955,1594–96.

18 “You are out of yourmind”:QuotedinTone,AgeofAnxiety,52.

19 Carter Products soldonly $7,500: “Onwardand Upward with the

Arts: Getting ThereFirst with Tranquility,”TheNewYorker,May3,1958.

20 In December,Americans bought$500,000:Restak,Poe’sHeart,187.

21“Ifthere’sanythingthismovie business needs”:QuotedinTone,Age ofAnxiety,57.

22 Lucille Ball’s assistantkept a supply: Tone,AgeofAnxiety,57.

23 “Miltowns, liquor,[and]swimming”:Ibid.

24 The actress TallulahBankhead:Ibid.,58.

25 “Hi, I’m MiltownBerle”: Restak, Poe’sHeart,187.

26a$100,000Miltownartinstallation: Tone, Age

ofAnxiety,76.27 “For the first time inhistory”: Restak, Poe’sHeart,187.

28“beofmarkedlygreaterimport”: Testimony ofNathan S. Kline, Falseand MisleadingAdvertisements(PrescriptionTranquilizing Drugs):Hearings Before a

Subcommittee of theCommittee onGovernment Operations,4.

29 Kline told a journalist:“Soothing, but Not forBusinessmen,”BusinessWeek, March10,1956.

30 By 1960, some 75percent: Tone, Age ofAnxiety,90.

31 “tense, anxious,Mediterranean-typepatients”: Shorter,History of Psychiatry,248.

32 “the insulin of thenervous”: Shorter,BeforeProzac,49.

33 “Thisstuff is sogood”:Valenstein, Blaming theBrain,27.

34 “the most dramatic

breakthrough”: Tone,AgeofAnxiety,80.

35 “No one in their rightmind”: Valenstein,BlamingtheBrain,27.

36 may have precipitatedWallace’s downwardspiral:See,forinstance,D. T. Max, “TheUnfinished,” The NewYorker,March9,2009.

37 “was the first cure”:

Kline,FromSadtoGlad,122.

38 the “sparks” and the“soups”: Valenstein,Blaming the Brain, 60–62.

39 “When I was anundergraduatestudent”: Quoted inAbbott, Alison,“Neuroscience: TheMolecular Wake-up

Call,” Nature 447, no.7143(2007):368–70.

40 Gaddum took LSD:Shorter, Before Prozac,69.

41 to give reserpine toevery single one:Valenstein, Blaming theBrain,69–70.

42administeringreserpineto rabbits: Healy,Creation of

Psychopharmacology,106,205–6.

43 Brodie’s 1955 paper:Alfred Pletscher,ParkhurstA.Shore,andBernard B. Brodie,“SerotoninReleaseasaPossible Mechanism ofReserpine Action,”Science 122, no. 3165(1955):374–75.

44 built a bridge from

neurochemistry tobehavior: Healy,AntidepressantEra,148.

45 In one of its firstadvertisements:Shorter, Before Prozac,52.

46 “Not infrequently thecure is complete”:Roland Kuhn, “TheTreatment ofDepressive States with

G 22355 (ImipramineHydrochloride),” TheAmerican Journal ofPsychiatry 115, no. 5(1958):459–64.

47 another accident ofhistory: Healy,Antidepressant Era, 52,58; Barondes, BetterThan Prozac, 31–32;Shorter, Before Prozac,61.

48 “These drugs seemedlike magic to me”:Shorter, Before Prozac,62.

49 In 1965, he publishedan article: Joseph J.Schildkraut, “TheCatecholamineHypothesis ofAffectiveDisorders: AReview ofSupporting Evidence,”TheAmericanJournalof

Psychiatry 122, no. 5(1965):509–22.

CHAPTER6:ABRIEFHISTORYOFPANIC

1 “The anxiety he feltlanding”: Sheehan,AnxietyDisease,37.

2 “Weassumeditwouldbe”: Donald F. Klein,“Commentary by aClinical Scientist inPsychopharmacologicalResearch,” Journal ofChild and Adolescent

Psychopharmacology 17,no.3(2007):284–87.

3significantorcompleteremission of theiranxiety: Donald F.Klein, “AnxietyReconceptualized,”ComprehensivePsychiatry 21, no. 6(1980):411.

4 “The predominantAmerican psychiatric

theory”: Quoted inKramer, Listening toProzac,80.

5 an initial report onimipramine: Donald F.Klein and Max Fink,“Psychiatric ReactionPatterns toImipramine,” TheAmerican Journal ofPsychiatry 119, no. 5(1962):432–38.

6 “like the proverbiallead balloon”: Quotedin Kramer, Listening toProzac,84.

7 Subsequent articlesover the next severalyears: Donald F. Klein,“Delineation of TwoDrug-ResponsiveAnxiety Syndromes,”Psychopharmacology 5,no.6(1964):397–408;

Klein and Oaks,“Importance ofPsychiatricDiagnosisinPrediction of ClinicalDrug Effects,” Archivesof General Psychiatry16,no.1(1967):118.

8 “the reaction of theindividual’s ego”:Quoted in Kramer,ListeningtoProzac,84.

9 “It is hard to recall”:

Kramer, Listening toProzac,77.

10 An advertisement foranOctober1956publictalk: Tone, The Age ofAnxiety,111.

11 “In this manner wewere able”: Shorter,History of Psychiatry,105.

12Actually,oneexceptionhere was astrologers:

MacDonald, MysticalBedlam,13–35.

13 “It is the task of theAPA”:Caplan,TheySayYou’reCrazy,234.

14 “a book of tentativelyassembledagreements”: Kutchinsand Kirk, Making UsCrazy,28.

15 “As the wine flowed”:David Sheehan,

“RethinkingGeneralized AnxietyDisorder andDepression” (remarksat a meeting of theAnxiety Disorders ofAmerica Association,Savannah, Ga., March7,2008).

16 “Invent a newtranquilizer”: Theaccount of Sternbach’s

discoveries is drawnfrom, among othersources, Baenninger etal.,GoodChemistry,65–78; Tone, Age ofAnxiety,120–40.

17 “We thought that theexpected negativeresult”: Leo Sternbach,“The Discovery ofLibrium,” Agents andActions 2 (1972): 193–

96.18tamedawildlynxwithLibrium: Smith, SmallComfort,74.

19 “TheDrugThatTamesTigers”: Quoted inDavenport-Hines,PursuitofOblivion,327.

20 “slightly soft in theknees”: Tone, Age ofAnxiety,130.

21 88 percent of those

with “free-floatinganxiety”: Joseph M.Tobin and Nolan D. C.Lewis, “NewPsychotherapeuticAgent,Chlordiazepoxide Usein Treatment ofAnxiety States andRelated Symptoms,”The Journal of theAmerican MedicalAssociation 174, no. 10

(1960):1242–49.22 “the most significantadvancetodate”:HarryH. Farb, “Experiencewith Librium inClinical Psychiatry,”Diseases of the NervousSystem21(1960):27.

23 “the treatment ofcommon anxieties”:Shorter, Before Prozac,100.

24 Librium had the samerange: M. Marinker,“The Doctor’s Role inPrescribing,” TheJournal of the RoyalCollege of GeneralPractitioners23,supp.2(1973):26.

25Valiumbecamethefirstdrug: Restak, Poe’sHeart,191.

26 one in every five

women: Valenstein,BlamingtheBrain,56.

27 18 percent of allAmerican physicians:George E. Vaillant,Jane R. Brighton, andCharles McArthur,“Physicians’ Use ofMood-AlteringDrugs:A20-Year Follow-upReport.” The NewEngland Journal of

Medicine(1970).28 “It is ten years sinceLibrium”: Quoted inSmith, Small Comfort,113.

29“Whethertheincrease”:Hollister,ClinicalUseofPsychotherapeuticDrugs,111.

30“Onemustconsiderthebroader implications”:D. Jacobs, “The

Psychoactive DrugThing: Coping or CopOut?,” Journal of DrugIssues 1 (1971): 264–68.

31 “35, single andpsychoneurotic”: See,for instance, TheAmerican Journal ofPsychiatry 126 (1970):1696. Theadvertisement also ran

in the Archives ofGeneralPsychiatry.

32 “the arrival of themillennium”:QuotedinSmith, Small Comfort,91.

33 “Valium, Librium, andotherdrugs”:QuotedinWhitaker, Anatomy ofanEpidemic,137.

34 the brains of peoplewho took tranquilizers:

M. H. Lader, M. Ron,and H. Petursson,“Computed Axial BrainTomography in Long-Term BenzodiazepineUsers,” PsychologicalMedicine 14, no. 1(1984): 203–6. Foradditional overview,see “Brain DamagefromBenzodiazepines,”Psychology Today,November18,2010.

CHAPTER7:MEDICATIONANDTHEMEANINGOFANXIETY

1 By2002, according toone estimate: M. N.Stagnitti, Trends inAntidepressant Use bythe U.S. Civilian Non-institutionalizedPopulation, 1997 and2002, Statistical Brief76 (Rockville, Md.:Agency for Healthcare

Research and Quality,May2005).

2a2007estimateputthenumber: United PressInternational, “Study:PsychDrugsSalesUp,”March28,2007.

3 Trace elements ofProzac: See, forinstance, “In OurStreams: Prozac andPesticides,” Time,

August 25, 2003;“RiverFishAccumulateHuman Drugs,” NatureNews Service,September 5, 2003;“Frogs, Fish, andPharmaceuticals: ATroubling Brew,”CNN.com, November14, 2003; “Prozac inthe Water,” Governing19, no. 12 (September2006); “Fish on Prozac

Are Violent andObsessive,”Smithsonian.com,November12,2012.

4 “Considering thebenefit and the risk”:Healy, Let Them EatProzac,39.

5 A series of studies inthe 1980s: Breggin,Talking Back to Prozac,49. See alsoHealy, Let

ThemEatProzac,37. 6 “This”: Shorter,BeforeProzac,172.

7 In 2006, EinarHellbom: EinarHellbom,“Chlorpheniramine,Selective Serotonin-Reuptake Inhibitors(SSRIs) and Over-the-Counter (OTC)Treatment,” Medical

Hypotheses 66, no. 4(2006): 689–90. SeealsoEinarHellbomandMats Humble, “PanicDisorder Treated withthe AntihistamineChlorpheniramine,”Annals of Allergy,Asthma, andImmunology 90 (2003):361.

8 David Wong, an Eli

Lillybiochemist:Healy,Let Them Eat Prozac,39.

9 a branding firm hadthought: “EternalSunshine,” TheObserver, May 12,2007.

10 “It is now clear”:Quoted in Barber,ComfortablyNumb,55.

11 “Paxil is truly

addictive”: Quoted inShorter, Before Prozac,44.

12 “do not have aclinically meaningful”:Joanna Moncrieff andIrving Kirsch, “Efficacyof Antidepressants inAdults,” British MedicalJournal 331, no. 7509(2005):155.

13 “If you’re born around

World War I”: Quotedin Barber, ComfortablyNumb,106.

14 In Iceland, theincidence ofdepression: TómasHelgason, HelgiTómasson, and TómasZoega,“Antidepressants andPublic Health inIceland: Time Series

Analysis of NationalData,” The BritishJournal of Psychiatry184,no.2(2004):157–62.

15 Britain reported 38million: JoannaMoncrieff and JocelinePomerleau, “Trends inSickness Benefits inGreat Britain and theContribution of Mental

Disorders,” Journal ofPublicHealth 22, no. 1(2000):59–67.

16 depression tripled inthe 1990s: RobertRosenheck, “TheGrowth ofPsychopharmacologyinthe 1990s: Evidence-Based Practice orIrrational Exuberance,”International Journal of

Law and Psychiatry 28,no.5(2005):467–83.

17 1,000 percent increase:See, for instance,Healy, Let Them EatProzac, 20. See alsoMcHenry, “EthicalIssues inPsychopharmacology,”Journal of MedicalEthics 32 (2006): 405–10.

18 the worldwide suiciderate has increased:www.who.int.

19ifadrugmakesyoufeelgood: Greenberg,ManufacturingDepression,193.

20“Psychotherapeutically”:Gerald L. Klerman, “AReaffirmation of theEfficacy ofPsychoactive Drugs,”

JournalofDrug Issues1(1971):312–19.

21 “Americans believetranquilizers areeffective”: Dean I.Manheimer et al.,“Popular Attitudes andBeliefs AboutTranquilizers,” TheAmerican Journal ofPsychiatry 130, no. 11(1973):1246–53.

22 only 38 percent ofAmericans: MentalHealth America,Attitudinal Survey2007.

23 only half had atypicallevels of serotonin:Marie Asberg et al.,“ ‘SerotoninDepression’—aBiochemical SubgroupWithin the Affective

Disorders?,” Science191, no. 4226 (1976):478–80.

24“abandonthesimplistichypothesis”: “CINPMeeting with theNobels, Montreal,Canada,June25,2002:Speaker’s Notes—Dr.Arvid Carlsson,”Collegium InternationaleNeuro-

PsychopharmacologicumNewsletter (March2003).

25 Not long ago, GeorgeAshcroft: L. McHenry,“Ethical Issues inPsychopharmacology,”Journal of MedicalEthics32,no.7(2006):405–10.

26 “theevidencedoesnotsupport”: Valenstein,

BlamingtheBrain,96.27 “We have hunted forbigsimple”:KennethS.Kendler, “Toward aPhilosophical Structurefor Psychiatry,” TheAmerican Journal ofPsychiatry 162, no. 3(2005): 433–40. Formore on the decayingof the serotoninhypothesis, see Jeffrey

R. Lacasse andJonathan Leo,“Serotonin andDepression: ADisconnectBetweentheAdvertisementsandtheScientific Literature,”PLoSMedicine2,no.12(2005):e392.

28 “If man can bereduced”: Tolson,Pilgrim,129.

29 “Yours is a mind”:QuotedinIbid.,191.

30 His opinion ofbiological psychiatry:Peter Kramer makesobservations alongthese lines in ListeningtoProzac.

31 “unable to account forthe predicament”: Thisessay is reprinted inPercy’s collection

Signposts in a StrangeLand.

32“Weallknowperfectlywell”: Quoted anddiscussed in, amongother sources,Elie,TheLife You Save, 276;Elliott and Chambers,ProzacasaWayofLife,135.

CHAPTER8:SEPARATIONANXIETY

1 “Fear disorders”: RonKessler, “Comorbidityof Anxiety Disorderswith Other Physicaland Mental Disordersin the NationalComorbidity SurveyReplication”(presentation at ADAAconference, Savannah,

Ga.,March7,2008). 2 “Anxiety in children”:Freud,ThreeEssays.

3“soulsburninginhell”:Breger, Dream ofUndyingFame,9.

4“libidotowardmatremhad awakened”: Gay,Freud,11.

5 “You yourself haveseen”: Breger, Freud,18.

6 “subject to attacks ofanxiety”: Kramer,Freud,20.

7 “a universal event inearly childhood”:Complete Letters ofFreudtoFliess,272.

8 “biological factor”:Freud, Problem ofAnxiety,99.

9 “the human infant issent”:Ibid.

10 “loss of love”: Ibid.,119.

11 “the atrophiedremnants of innatepreparedness”: Ibid.,117.

12 “was a very stablebackground”: Karen,BecomingAttached,30.

13 “a sharp, hard, self-centered woman”:Ibid.,31.

14 “could be seen as anindictment”:Ibid.

15 “But there is such athing”: Bowlby,Separation,viii.

16 “a frightfully vain oldwoman”: Karen,BecomingAttached,44.

17 “anextremelyanxious,distressed woman”:Ibid.,45.

18“Thefactthatthispoor

woman”:Ibid.19 When Ainsworth firstarrivedinUganda:Thisaccount of Ainsworth’stime in Uganda drawsheavily on her bookInfancy in Uganda andonchapter11ofRobertKaren’s BecomingAttached.

20 none of theambivalently attached

children: Karen,BecomingAttached,180.

21 Konrad Lorenz’sinfluential 1935 paper:KonradZ.Lorenz,“TheCompanion in theBird’sWorld,”The Auk54, no. 3 (1937): 245–73.

22 “What’s the use topsychoanalyze agoose?”: Quoted in

Karen, BecomingAttached,107.

23 calls to“excommunicate” him:Issroff, Winnicott andBowlby,121.

24publishedanarticlein:Harry FrederickHarlow,“TheNatureofLove,” AmericanPsychologist (1958):673–85.

25 “Thereafter”: Bowlby,SecureBase,26.

26 when infant monkeyswereseparated:See,forinstance, YvetteSpencer-Booth andRobert A. Hinde,“Effects of 6 DaysSeparation fromMother on 18- to 32-Week-Old RhesusMonkeys,” Animal

Behaviour 19, no. 1(1971):174–91.

27 AsubsequentpaperbyHarryHarlow:HarryF.Harlow and MargaretHarlow, “Learning toLove,” AmericanScientist 54, no. 3(1966):244–72.

28 “initiation of ventralcontact”: See, forinstance, Stephen J.

Suomi, “How Gene-EnvironmentInteractions Can Shapethe Development ofSocioemotionalRegulation in RhesusMonkeys,” EmotionalRegulation andDevelopmental Health:Infancy and EarlyChildhood (2002): 5–26.

29 The idea behind thevariable foragingdemand: See, forinstance,Mathewetal.,“Neuroimaging Studiesin Nonhuman PrimatesReared Under EarlyStressful Conditions,”Fear and Anxiety(2004).

30 he died alcoholic anddepressed: See, for

instance, Blum,Love atGoonPark.

31 the amount of lickingand grooming: See, forinstance, ChristianCaldji et al., “MaternalCare During InfancyRegulates theDevelopment ofNeuralSystems Mediating theExpression ofFearfulnessintheRat,”

Proceedings of theNational Academy ofSciences 95, no. 9(1998):5335–40.

32lastingconsequencesona primate’sneurochemistry: See,for instance,JeremyD.Coplanetal.,“VariableForaging DemandRearing: SustainedElevations in Cisternal

Cerebrospinal FluidCorticotropin-ReleasingFactor Concentrationsin Adult Primates,”BiologicalPsychiatry50,no.3(2001):200–4.

33 There’s even someevidence: See, forinstance, Tamashiro,KellieL.K., “MetabolicSyndrome: Links toSocial Stress and

Socioeconomic Status,”Annals of theNewYorkAcademy of Science1231,no.1(2011):46–55.

34 the children and evengrandchildren: See, forinstance, Joel J.Silverman et al.,“Psychological Distressand Symptoms ofPosttraumatic Stress

Disorder in JewishAdolescents Followinga Brief Exposure toConcentration Camps,”Journal of Child andFamily Studies 8, no. 1(1999):71–89.

35 A recent studypublished: Maselko etal., “Mother’sAffectionat 8 Months PredictsEmotional Distress in

Adulthood,” Journal ofEpidemiology &Community Health 65,no.7(2011):621–25.

36acopingstrategybasedon “chronic vigilance”:See, for instance, L.Alan Sroufe,“Attachment andDevelopment: AProspective,Longitudinal Study

from Birth toAdulthood,”AttachmentandHumanDevelopment7, no. 4 (2005): 349–67.

37 “Adults withagoraphobia are morelikely”: Corine deRuiter and Marinus H.Van Ijzendoorn,“Agoraphobia andAnxious-Ambivalent

Attachment: AnIntegrative Review,”Journal of AnxietyDisorders 6, no. 4(1992):365–81.

38 “Adults withagoraphobia report”:Dozier et al.,“Attachment andPsychopathology inAdulthood,” inHandbook of

Attachment,718–44.39“[Infantswithinsecure]attachments”: Warren,et al., “Child andAdolescent AnxietyDisorders and EarlyAttachment,”Journalofthe American Academyof Child & AdolescentPsychiatry 36, no. 5(1997):637–44.

40 “Human adults who

reported”: Hane, AmieAshley, and Nathan A.Fox, “Ordinaryvariations in maternalcaregiving influencehuman infants’ stressreactivity,”Psychological Science17.6(2006):550–556.

CHAPTER9:WORRIERSANDWARRIORS

1 In 2001, KennethKendler: Kenneth S.Kendler et al., “TheGenetic Epidemiologyof Irrational Fears andPhobias in Men,”Archives of GeneralPsychiatry 58, no. 3(2001): 257. See alsoKenneth S. Kendler,

JohnMyers, and CarolA. Prescott, “TheEtiologyofPhobias:AnEvaluation of theStress-DiathesisModel,” Archives ofGeneral Psychiatry 59,no.3(2002):242.

2 Meta-analyses ofgeneticstudies:See,forinstance, Hettema etal., “A Review and

Meta-Analysis of theGenetic Epidemiologyof Anxiety Disorders,”TheAmericanJournalofPsychiatry 158, no. 10(2001)1568–78.

3oneofthelargest-scalestudies: GiovanniSalum, “Anxiety‘Density’ in FamiliesPredicts Disorders inChildren” (presentation

at ADAA conference,March28,2011).

4 “Webelieve thatmostofthechildren”:quotedin Restak, Poe’s Heart,64; see also Kagan,Unstable Ideas, 161-163.

5 Kagan and hiscolleagues took brainscans:Thesestudiesaredescribed in Robin

Marantz Henig,“Understanding theAnxious Mind,” TheNew York TimesMagazine, September29,2009.

6 MicewhoseGrp gene:See, for instance, GlebP. Shumyatsky et al.,“Identification of aSignaling Network inLateral Nucleus of

Amygdala Importantfor Inhibiting MemorySpecifically Related toLearned Fear,” Cell111,no.6(2002):905–18.

7 Mice whose stathmingene: See, for instance,Gleb P. Shumyatsky etal., “Stathmin, a GeneEnriched in theAmygdala, Controls

Both Learned andInnate Fear,” Cell 123,no.4(2005):697–709.

8 In one study ofchildren:Smolleretal.,“Influence of RGS2 onAnxiety-RelatedTemperament,Personality, and BrainFunction,” Archives ofGeneral Psychiatry 65,no.3(2008):298–308.

9 Another study, of 744college students: Citedin Smoller et al.,“Genetics of AnxietyDisorders:TheComplexRoad from DSM toDNA,” Depression andAnxiety 26, no. 11(2009):965–75.

10Athirdstudyrevealed:Leygraf et al., “RGS2GenePolymorphismsas

Modulators of AnxietyinHumans,” Journal ofNeural Transmission113, no. 12 (2006):1921–25.

11 A fourth study, of 607people: Koenen et al.,“RGS2 andGeneralizedAnxiety Disorder in anEpidemiologic Sampleof Hurrican-ExposedAdults,”Depression and

Anxiety 26, no. 4(2009):309–15.

12 Lauren McGrath, aresearcher: “UniqueStudy Identifies GeneAssociated withAnxious Phenotypes,”Medscape News, March29,2011.

13 “talent for creativedanceperformance”:R.Bachner-Melman et al.,

“AVPR1a and SLC6A4Gene PolymorphismsAre Associated withCreative DancePerformance,” PLoSGenetics 1, no. 3(2005):e42.

14 tend to have a hardertime: See, for instance,“Catechol O-methyltransferaseVal158met Genotype

and NeuralMechanisms Related toAffective Arousal andRegulation,”ArchivesofGeneral Psychiatry 63,no. 12 (2006): 1,396.Also, Montag et al.,“COMT GeneticVariation Affects FearProcessing:PsychophysiologicalEvidence,” BehavioralNeuroscience122,no.4

(1008):901.15 One study, conductedby investigators:Enochet al., “Genetic Originsof Anxiety in Women:ARoleforaFunctionalCatechol-o-methyltransferasePolymorphism,”Psychiatric Genetics 13,no.1(2003):33–41.

16 Another study,

conductedamongboth:Armbruster et al.,“Variation in GenesInvolved in DopamineClearanceInfluencetheStartle Response inOlder Adults,” Journalof Neural Transmission118, no. 9 (2011):1281–92.

17 David Goldman, thechief of human

neurogenetics: See, forinstance, Stein et al.,“Warriors versusWorriers: The Role ofCOMT Gene Variants,”CNS Spectrums 11, no.10 (2006): 745–48.Also, “Finding the‘Worrier-Warrior’Gene,” PhiladelphiaInquirer,June2,2003.

18 These different

evolutionary strategies:Cited in Stein andWalker, Triumph overShyness,21.

19 Starting in the mid-1990s: For instance,Lesch, et al.,“Association ofAnxiety-Related Traitswith a Polymorphismin the SerotoninTransporter Gene

Regulatory Region,”Science 274, no. 5292(1996): 1527–31. Also,Hariri, Ahmad R., etal., “SerotoninTransporter GeneticVariation and theResponseoftheHumanAmygdala.” Science297, no. 5580 (2002):400–403. (For a good,non-technical overviewof this research, see

Dobbs, “TheScienceofSuccess,” The Atlantic,December2009.)

20 Ressler found that thevariant: Charles F.Gillespie et al., “RiskandResilience:Geneticand EnvironmentalInfluences onDevelopment of theStress Response,”Depression and Anxiety

26,no.11(2009):984–92.SeealsoRebekahG.Bradley et al.,“Influence of ChildAbuse on AdultDepression:Moderationby the Corticotropin-Releasing HormoneReceptor Gene,”Archives of GeneralPsychiatry 65, no. 2(2008): 190; Kerry J.Ressler et al.,

“Polymorphisms inCRHR1 and theSerotonin TransporterLoci: Genex GenexEnvironmentInteractions onDepressive Symptoms,”American Journal ofMedicalGenetics,PartB:NeuropsychiatricGenetics 153, no. 3(2010):812–24.

21Variationsinthisgene:Ibid.SeealsoElisabethB. Binder et al.,“Association of FKBP5Polymorphisms andChildhood Abuse withRisk of PosttraumaticStress DisorderSymptoms in Adults,”The Journal of theAmerican MedicalAssociation 299, no. 11(2008): 1291–305;

Divya Mehta et al.,“Using Polymorphismsin FKBP5 to DefineBiologically DistinctSubtypes ofPosttraumatic StressDisorder: Evidencefrom Endocrine andGene ExpressionStudies,” Archives ofGeneral Psychiatry(2011):archgenpsychiatry-

2011.22 A 2005 study at SanDiego State University:Stein, Murray B.,Margaret DanieleFallin, Nicholas J.Schork, and JoelGelernter. “COMTPolymorphisms andAnxiety-relatedPersonality Traits.”Neuropsychopharmacology

30, no. 11 (2005):2092–2102.

23 In the 1970s, MartinSeligman: Martin E. P.Seligman,“PhobiasandPreparedness,”BehaviorTherapy 2, no. 3(1971):307–20.

24 monkeys could noteasily acquire fears:SusanMinekaandArneÖhman, “Born to Fear:

Non-associative Vs.Associative Factors inthe Etiology ofPhobias,” BehaviourResearch and Therapy40, no. 2 (2002): 173–84.

25 This is evidence,Öhman argues: Öhmanand Mineka, “Fears,Phobias, andPreparedness: Toward

an Evolved Module ofFear and FearLearning,”PsychologicalReview 108, no. 3(2001):483.

CHAPTER10:AGESOFANXIETY

1 “the brain-workers inalmost everyhousehold”: Beard, APracticalTreatise,1.

2 “In the oldercountries”: A. D.Rockwell, “SomeCauses andCharacteristics ofNeurasthenia,” NewYorkMedicalJournal58

(1893):590.3“Americannervousnessis the product”: Beard,American Nervousness,176.

4 “The Greeks werecertainly civilized”:Ibid.,96.

5“modern,andoriginallyAmerican”: Ibid., vii–viii.

6“Whencivilization,plus

these five factors”:Ibid.,96.

7 Thecrucial concept inall these explanations:See, for instance,Micale, Hysterical Men,23.

8“Ibeginwiththeheadand brain”: Beard,PracticalTreatise,15.

9 “destroyed or mademiserable”: Quoted in

Micale, Hysterical Men,35.

10 “a veritable socialplague”: Quoted inMicale, Hysterical Men,35.

11 “One of my patientstellsme”:Ibid.,53.

12 “One of my cases”:Ibid.,54.

13 “One man was soafraid”:Ibid.,60.

14 neurasthenia hadpermeated deep: For adetailed exploration ofthis,seeLutz,AmericanNervousness; Schuster,NeurasthenicNation.

15 “overstressed nation”:AmericanPsychologicalAssociation, Stress inAmerica,2010.

16 increased from 13.4millionto16.2million:

IMS Health Data,National Disease &Therapeutic Index,DiagnosisVisits, 2002–2006.

17 More Americans seekmedical treatment:Ibid.

18 A study published inthe AmericanPsychologist: Swindle etal., “Responses to

NervousBreakdownsinAmericaovera40-yearperiod,” AmericanPsychologist 55, no. 7(2000):740.

19 Twice asmany peoplereported: Goodwin,Renee D., “ThePrevalence of PanicAttacks in the UnitedStates: 1980 to 1995,”Journal of Clinical

Epidemiology 55, no. 9(2003):914–16.

20 the average collegestudent in the 1990s:Twenge,GenerationMe,107.

21 “The average highschool kid today”:“HowBig aProblem isAnxiety?” PsychologyToday,April30,2008.

22 A World Health

Organization survey:Kessleretal.,“LifetimePrevalence and Age-of-Onset Distributions ofMentalDisordersintheWorld HealthOrganization’s WorldMental Health SurveyInitiative,” WorldPsychiatry 6, no. 3(207):168.

23 Statistics from the

National HealthService: “AnxietyDisorders Have SoaredSince Credit Crunch,”The Telegraph, January1,2012.

24 “culture of fear”:Mental HealthFoundation, Facing theFear,April2009.

25 the odds in favor ofdamnation: LeGoff,

Medieval Civilization,325.

26“ThemajorproblemforAmericans”: Slater,PursuitofLoneliness,24.

27 “the paradox ofchoice”: Schwartz,Paradox of Choice, 2,43.

28 “From the moment ofbirth”: Fromm, EscapefromFreedom,41.

29 “First of all a feeling”:Tillich, Protestant Era,245.

30 “Fascism was like ajail”: Quoted in May,MeaningofAnxiety,12.

31 “It has filled the”:TheNew York Times,February1,1948.

32 “people grasp atpoliticalauthoritarianism”:

May, Meaning ofAnxiety,12.

33 “for 99 percent ofhuman history”:Sapolsky’sdiscussionofthis appears in Zebras,378–83.

34 excessive timidity,caution, and concern:Kagan, What IsEmotion?,14.

35 “Competitive

individualism militatesagainst”:May,MeaningofAnxiety,191.

36 “troubles herself withevery thing”: Hunterand Macalpine, ThreeHundred Years ofPsychiatry,116.

37 “Intolerance ofuncertainty appears tobe”: Michel J. Dugas,Mark H. Freeston, and

Robert Ladouceur,“Intolerance ofUncertainty andProblemOrientation inWorry,” CognitiveTherapy and Research21, no. 6 (1997): 593–606.

38 a 31 percent increase:Scott Baker, NicholasBloom, and StevenDavis, “Measuring

Economic PolicyUncertainty” (ChicagoBooth Research Paper13-02,2013).

39 “nervous complaintsprevail at the presentday”: Quoted inOppenheim, “ShatteredNerves,”14.

40 “At the beginning ofthe nineteenthcentury”: Quoted in

Micale, Hysterical Men,81.

41“atrociousandfrightfulsymptoms”: Cheyne,The English Malady,xxx.

42 “Other men get theirknowledge”: Burton,Anatomy,BOOKI,34.

43 “I write ofmelancholy”:Ibid.,21.

44 “Many lamentable

effects this fearcauseth”:Ibid.,261.

45 “Many men are soamazed”:Ibid.

46 “There is no greatercause”:Ibid.,21.

47 “Ifmenwouldattemptnomore”:Ibid.,50.

48 “In our day we stillsee”: May, Meaning ofAnxiety,xiv.

CHAPTER11:REDEMPTION

1 Eliot was, Kaganobserves: Kagan hasmade this observationinnumerousplaces.

2 “saturated with thevocabulary”: Micale,HystericalMen,214.

3 “whether among allthose Scholars”:QuotedinIbid.

4 Dean Simonton, apsychologist:Simonton,“Are Genius andMadness Related?ComtemporaryAnswers to an AncientQuestion,” PsychiatricTimes22,no.7(2005):21–23. See also “TheCase for Pessimism,”Businessweek, August13,2004.

5 But his early lettersreveal otherwise:Lettersquotedherearefrom Masson, CompleteLetters.

6 “They’re compulsive,they don’t makeerrors”: Quoted inRobin Marantz Henig,“Understanding theAnxious Mind,” TheNew York Times

Magazine, September29,2009.

7 A 2012 study bypsychiatrists: NicholasA.Turianoetal.,“Big5Personality Traits andInterleukin-6: Evidencefor ‘HealthyNeuroticism’ in a USPopulation Sample,”Brain, Behavior, andImmunity(2012).

8 A 2013 study in theAcademy ofManagement Journal:Corrine Bendersky andNeha Parikh Shah,“The Downfall ofExtrovertsandtheRiseof Neurotics: TheDynamic Process ofStatus Allocation inTask Groups, Academyof ManagementJournal,” AMJ-2011-

0316.R3. 9 “I would staff it withmore neurotics andfewer extroverts”:“Leadership Tip: HiretheQuietNeurotic,Notthe ImpressiveExtrovert,” Forbes,April11,2013.

10 In2005,researchersatthe University ofWales: Adam M.

Perkins and Philip J.Corr, “CanWorriersBeWinners? TheAssociation BetweenWorrying and JobPerformance,”Personality andIndividual Differences38, no. 1 (2005): 25–31.

11 high IQ scorescorrelated with high

levels: Jeremy D.Coplan et al., “TheRelationship BetweenIntelligence andAnxiety:AnAssociationwith Subcortical WhiteMatter Metabolism,”Frontiers inEvolutionaryNeuroscience3(2012).

12 a certain interpersonalobtuseness: SeeWinifred Gallagher,

“How We BecomeWhat We Are,” TheAtlantic, September1994.

13 But recent studies onrhesus monkeys:Stephen J. Suomi,“Risk, Resilience, andGene-EnvironmentInterplay in Primates,”Journal of theCanadianAcademy of Child and

Adolescent Psychiatry20, no. 4 (November2011):289–97.

CHAPTER12:RESILIENCE

1 the constant beratingby Johnson’s superego:Bate, Samuel Johnson,117–27.

2 The ten criticalpsychologicalelements:Charney, “ThePsychobiology ofResilience to ExtremeStress: Implications forthe Treatment and

Prevention of AnxietyDisorders,” keynoteaddress at ADAAconference, March 23,2006.

3 the work of thecognitive psychologist:See,forinstance,AlbertBandura,“Self-Efficacy:Toward a UnifyingTheory of BehavioralChange,” Psychological

Review 84, 191–215;Albert Bandura, “TheAssessment andPredictiveGeneralityofSelf-Percepts ofEfficacy,” Journal ofBehavior Therapy andExperimental Psychiatry13,195–99.

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ANOTEABOUTTHEAUTHOR

Scott Stossel is the editorofThe Atlantic. He is alsothe author of Sarge: TheLife and Times of SargentShriver, and his articlesand essays have appearedin The New Yorker, TheNew Republic, The NewYorkTimes,TheWallStreetJournal, and many other

publications.Heliveswithhis family in Washington,D.C.

ALSOBYSCOTTSTOSSEL

Sarge:TheLifeandTimesofSargentShriver