How the Circadian Rhythm Affects Sleep, Wakefulness, And Overall Health

8/12/2019 How the Circadian Rhythm Affects Sleep, Wakefulness, And Overall Health

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The CircadianRhythm and its

disorders

PROF. DRA. ROSEMARIE FRITSCH

MATERIAL DOCENTE


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ANDREW D. KRYSTAL,MD,MS

How the Circadian RhythmAffects Sleep, Wakefulness,

and Overall Health
http://www.psychiatrist.com/podcast/player.asp?url=http://www.psychiatrist.com/briefreports/audio/BR1krystalINTRO.mp3&title=Brief%20Reports:%20How%20the%20Circadian%20Rhythm%20Affects%20Sleep,%20Wakefulness,%20and%20Overall%20Health:%20Background%20for%20Understanding%20Shift%20Work%20Disorder:%20Diagnosing%20Bipolar%20Disorder:%20Signs%20and%20Symptoms&author=Andrew%20D.%20Krystal,%20MD,%20MS%20&duration=1:02http://www.psychiatrist.com/podcast/player.asp?url=http://www.psychiatrist.com/briefreports/audio/BR1krystalINTRO.mp3&title=Brief%20Reports:%20How%20the%20Circadian%20Rhythm%20Affects%20Sleep,%20Wakefulness,%20and%20Overall%20Health:%20Background%20for%20Understanding%20Shift%20Work%20Disorder:%20Diagnosing%20Bipolar%20Disorder:%20Signs%20and%20Symptoms&author=Andrew%20D.%20Krystal,%20MD,%20MS%20&duration=1:02


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1

Properties of the CircadianRhythm

The field of circadian rhythmresearch was launchedin the early 18th century (AV 1).1 The circadian rhythmentrains an organisms functions to the environmentalcycle of light and dark. This rhythm is seen in nearly all

species and plays an important role in synchronizingorgan systems to optimal phase relationships with eachother. Variations in many biological processes occurover roughly a 24-hour period (AV 2).

This type of endogenous rhythmicityis also seen inmany other biological measures. For example, levels of

plasma melatonin increase in the evening and earlypart of the night, while levels of plasma cortisolincrease over the course of the night, peak at waking,and diminish throughout the day.2

Our innate circadian rhythm can be modified by anumber of factors, especially light. For example, whenyou travel to a new time zone, your body is on a

different schedule from the new environment, becauseit continues to function for some time on the circadianrhythm you developed in your previous location. Thelonger you stay in the new environment, the more yourbody aligns with its new environmental clock. Thisprocess is driven by cues, especially exposure to light,which tells us when it is day or night.

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Light has different effects on the circadian rhythmdepending on when we are exposed to it.1Thus, if weare exposed to light late during the night, this shiftsour rhythm so that we tend to go to bed and wake upearlier. If we are exposed to light in the early part of thenight, this shifts our rhythm so that we tend to stay upand sleep later. Exposure to light during the period

when we are usually awake has no effect at all.

Other factors that can affect our internal clock includewhen we eat, our activity level, and caffeine intake.3,4Thus we often have gastrointestinal upsets in a newtime zone because we are eating when our body doesnot expect to eat (ie, our digestive hormones are out of

synch with our meal time).5 Our innate circadianrhythm also affects how our autonomic nervous systemand our brain function.6

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Anatomy of the CircadianRhythm

The important role of the suprachiasmatic nucleus(SCN) in regulating periodic behavior7has beenconfirmed by a number of findings in animal studies(AV 3).

1. When the SCN is lesioned, circadianrhythmicity goes away because the SCN is no longerable to stimulate the production of melatonin andother substances that modulate the sleep-wakepattern.8

2. If cells are removed from the SCN and grownin vitro, they continue to show self-sustaining circadianrhythmicity.9

3. If the SCN is transplanted from one animal toanother, the recipient manifests the circadian rhythmof the donor, showing that the SCN can entrainbiological activity and drive a circadian process on its

own.10

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Genetics of the CircadianRhythm

Although researchers had been able to breed forchanges such as different eye or hair color for a longtime, it was not until the 1960s that Benzer firstdemonstrated that behavior could be modifiedgenetically by breeding circadian behavioral patternsinto fruit flies.11This demonstrated that the chemicalclock in the SCN is under genetic control. A relatively

small number of genes and proteins regulate thisbiological clock. The critical components of this geneticsystem are the Period, Clock, and Cryptochrome (Cry)genes, and these can be manipulated to alter thecircadian cycle.12

The role of genetic factors in our circadian rhythm issupported by the observation that preferred

sleep/wake schedules (eg, being a night owl or a morning lark) tend to run in families. The tendency togo to bed and get up very early (sleep phase advance),is linked to a mutation in the human Period-2 (hPer2)gene that is an autosomal dominant trait.13Thetendency to stay up late and sleep late (sleep phase

delay) is associated with several genes, including thehuman Period-3 (hPer3) gene.14

In humans, the circadian rhythm is controlled byseveral core genes that operate via a series of feedbackloops (Figure 1). A transcriptiontranslation

negative-feedback loop powers the system, with a delaybetween the transcription of these genes and thenegative feedback being a key factor that allows thesystem to oscillate.

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Effects on Sleep/WakeFunction

The SCN regulates our sleeping and waking through itseffect on 3 brain regions7:

! Ventrolateral preoptic area: releases "-aminobutyric acid (GABA) and promotes sleep

! Lateral hypothalamic area: releases thetransmitter hypocretin/orexin that promoteswakefulness

! Paraventricular hypothalamus: involvedin the release of melatonin

The interaction shown in the sleep/wake model15produces a consolidated period of wakefulness, drivenby the circadian rhythm, and a consolidated period of

sleep that occurs when the homeostatic drive to sleephas built up and the wake-promoting systems haveshut down (AV 4).16The circadian rhythm systemenables us to stay awake for extended periods, despitea growing homeostatic drive for sleep. It does this by

modulating the release of neurotransmitters, inparticular hypocretin/orexin, that maintainwakefulness. Otherwise, we would have great difficultyfunctioning, since we would fall asleep as soon as agreat enough drive to sleep had built. This is whathappens in narcolepsy, which involves abnormalities inthe hypocretin/orexin system.17

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Process S representsthe homeostatic

built-up of sleeppressure

Process C representsthe circadian rhythm

When the distancebetween process S and

process C is largest,sleep propensity willbe highest.

Borblys model of sleep-wake regulation (Borbly & Achermann, 1999).


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Here you can see how sleep pressure keeps building up due to sleep deprivation, but since the circadian rhythmkeeps fluctuating by its regular 24 hour cycle, our sleep propensity will also fluctuate with this rhythm. In additionthis picture also shows that such sleep deprivation will lead to a higher slow wave activity (SWA, representingdeeper stages of sleep) during the recovery sleep. This type of activity is used as a marker for the homeostaticprocess. When we for example go to bed earlier when homeostatic sleep pressure hasnt built up that much, this willtranslate into less slow wave activity. Even within a sleep cycle itself you can see this phenomenon, with lessslow-wave activity during the second part of the sleep.

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Problems in Sleep/WakeFunction

Problems can occur when the drive for wakefulnessand the drive for sleep are not correctly synchronized.Thus, if you try to sleep when your body doesntnormally sleep, you will sleep less and you will notsleep as well because your circadian processes are

fighting the sleep drive. Individuals with circadianrhythm sleep disorders often experience at least partialsleep loss on a long-term basis. This is because they aretrying to sleep at an unfavorable time for extendedperiods. Even modest prolonged sleep deprivation canproduce 4 types of serious physiologicalabnormalities18-23:

! Metabolic dysfunction (increased appetite,metabolism, or oxygen consumption; sympatheticnervous system activation; decreased cerebral glucoseutilization in certain subcortical structures)

! Neuroendocrine abnormalities(lowthyroid-stimulating hormone; decreased levels ofgrowth hormone, prolactin, or leptin)

! Decreased resistance to infectiousdisease

! Oxidative stress

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Humans who experience prolonged sleep deprivationalso demonstrate higher rates of obesity and type 2diabetes and neurobehavioral impairment, including ashortening of voluntary and involuntary sleep latencyresulting in daytime sleepiness, microsleeps (intrusion

of sleep into wakefulness), and errors of omission andcommission on cognitive testing.24,25

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6

Role of the CircadianRhythm in Health and

Disease

By synchronizing the bodys biological clocks, the SCNhas extensive influence on peripheral tissues through

the autonomic nervous system.26

For example, glucoseis released in a gradual, oscillating, sinusoidal-likepattern over a 24-hour period. If animals are fed attimes other than their natural feeding times, theoriginal cycle continues. However, if you cut out theSCN, glucose release becomes entrained to feedingtimes and is no longer linked to other physiologic

processes related to eating and digestion.27

Phase dyssynchrony occurs when the rhythms oforgans are out of synch with the SCN. Research inanimals and humans has shown that such disruptionscan have negative effects on health. For example, onestudy found that disrupting the normal circadian

rhythmicity of hamsters with cardiomyopathy reducedtheir median life span by 11%.28In the next chapter, DrRoth will discuss the types of negative effects that canoccur in humans who experience such phasedyssynchrony, as occurs when someone has Shift Work

Disorder.

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The circadian rhythm, a self-sustainedrhythm of biological processes observedin nearly all species, is determined by

both genetic and behavioral factors. Itplays an important role in coordinatingand modulating sleep/wake function andin many other biological processes.Disturbances of the circadian rhythmcause misalignment among biologicaland behavioral processes that can lead to

disturbances in sleep/wake function andother types of impaired functioning andmay affect our capacity to fight offdisease.

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Summary

Pregunta 1 de 4The circadian rhythm is

A. The determinant of cicada

lifecyclesB. A self-sustained rhythm of

biological processes observed innearly all species

C. Another name for jet lag


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THOMAS ROT H,PHD

Shift Work Disorder:Overview and Diagnosis
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Circadian Rhythm SleepDisorders

According to the second edition of the AmericanAcademy of Sleep Medicines International

Classification of Sleep Disorders (ICSD-2),1

the majorfeature of circadian rhythm sleep disordersis amisalignment between the patients sleep pattern andthe sleep pattern that is desired or regarded as thesocietal norm (AV 1).

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In addition to shift work disorder(SWD), theICSD-2 lists 8 other types of circadian rhythm sleepdisorders, including time zone change (jet lag)syndrome and delayed and advanced sleep phasesyndromes. Many people have experienced jet lag

syndrome, caused by a lack of synchrony between yourinternal clock and a new time zone in which you aretrying to function. Circadian rhythm disturbances canalso involve delayed or advanced sleep phases(AV 2).

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Because delayed and advanced sleep phase syndromesoften cause the person to be out of synchrony with theprevailing sleep/wake patterns of society, they can leadto significant morbidity. Recent studies2-5have found

that, when high school classes were started an hour ortwo later, the number of car accidents decreased andacademic functioning improved. Problems can alsoarise when there is chronic dyssynchrony between thepersons internal clock and external light and dark (ie,when a person is required to stay awake and workwhen it is dark and sleep when it is light), which can, in

some cases, lead to SWD.

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Shift Work

It is important to distinguish between shift work andSWD. Shift work is a job description. The vast majority

of people who work shifts adjust and do well. However,a subgroup of people have great difficulty adjustingtheir internal clocks and develop SWD due to amismatch between the sleep/wake schedule requiredby theirjobs and their own circadian sleep/wakecycles.

Prevalence. It is estimated that 15%26% of the US

labor force works night, evening, or rotating shifts (AV3).6,7

Effects of shift work on the sleep/wake cycle.Shift work affects the sleep/wake cycle in a number ofways. No matter how many hours you have sleptduring the day, trying to work during the downside ofthe circadian rhythm (eg, between 12 AM and 6 AM) isvery difficult unless you can shift your internal clock.Studies have found that, over a 24-hour cycle, bothsubjective alertness and cognitive functioning decline

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between 2 AM and 4 AM.8 Also, because you are notsleeping at night, the homeostatic pressure to sleep isnot relieved, producing an ever-increasing pressure tosleep.9However, only a subset of individuals who worknight or rotating shifts develop SWD, becausecircadian rhythms are modulated not only by light anddark, but also by other factors such as clock genes,melatonin, and environmental cues (eg, noise).10,11

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Shift Work Disorder: AnOverview

Prevalence.

Drake et al12 found that 28% of those who work nightor rotating shifts, compared with 18% of day workers,experienced insomnia and/or excessive sleepiness, andthey estimated the true prevalence of SWD to beapproximately 10% of those who work night or rotatingshifts. A study of 103 shift workers on a North Sea oilrig (working 2 weeks on 7 nights/7 days, 12-hour shifts,4 weeks off) by Waage et al13 found a relatively high

prevalence of SWD. They reported that 24 (23.3%) ofthe shift workers were suffering from SWD and that,during their 4-week period off work, the workers withSWD reported significantly poorer sleep quality, moresubjective health complaints, and greater problems incoping than individuals who did not have SWD. Shift

workers without SWD reported results similar to thoseof day workers on the rig with regard to sleep,sleepiness, subjective health complaints, and coping.

Diagnosis.

The ICSD-2 diagnostic criteria for circadian rhythmsleep disorder, shift work type, are shown in (AV 4).The differential diagnosis of SWD includes excessivesleepiness due to obstructive sleep apnea, narcolepsy,restless legs syndrome, and chronic insufficient sleepdue to daytime conflicts (eg, child care, environmentalfactors, moonlighting at a second job). Comorbidconditions (eg, increased prevalence of sleep apnea inshift workers) can complicate the diagnosis of SWD.Clinicians should also rule out comorbid disorders thatcan cause insomnia and excessive sleepiness (eg,primary insomnia, insomnia associated withpsychiatric disorders such as major depression), aswell as consider whether the person may be takingmedications or abusing drugs or alcohol to help withsleep, which may be causing impairment at work.

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Consequences of ShiftWork Disorder

Just as animal studies have found that disruptions incircadian rhythm can affect health outcomes, studies in

humans have produced similar findings.Gastrointestinal problems(eg, ulcers, functionalbowel disorders) are significantly increased inindividuals who work night or rotating shifts. However,the increased prevalence of ulcers is associated not justwith shift work, but also with SWD. In a studycomparing 360 workers on rotating shifts, 174 on night

shifts, and 2,036 on day shifts, Drake et al12 foundthat, among those who reported excessive sleepinessand/or insomnia, the prevalence of ulcers was higheramong rotating shift workers (12.5%) and night shiftworkers (15.4%) than day workers (6%). This effect wasnot seen to any marked degree in those who worked

rotating or night shifts but did not have excessivesleepiness and/or insomnia. Zhen Lu et al14 found thatthe prevalence of functional bowel disorders washigher in a sample of nurses who worked rotatingshifts (38%) than in those who worked day shifts (20%)and that functional bowel disorder symptoms werepositively correlated with level of sleep disturbance.

Cancer. Shift work (whether or not the person hasSWD) has been found to be a risk factor for cancer.Increased odds ratios for breast cancer have beenfound in large samples of women who worked nightshifts, particularly with increasing duration of

nighttime employment.15-19 A study20 of 14,052working men in Japan also found a significantlyincreased risk of prostate cancer in those who workedrotating shifts. The World Health OrganizationInternational Agency for Research on Cancer hasconcluded, Shift work that involves circadiandysruption is probably carcinogenic to humans.21

Depression. The prevalence of depression issignificantly higher in those who work rotating andnight shifts than in day workers. In addition, whileinsomnia or daytime sleepiness is a risk factor fordepression for all individuals, it is a much greater riskfactor for rotating or night shift workers.12

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Cardiovascular effects. While insomnia is a riskfactor for hypertension in all individuals, it is asignificantly higher risk factor for shift workers withinsomnia.12 In contrast, although shift work isassociated with a significantly increased risk of heartdisease compared with nonshift work, this increasedrisk is not associated with SWD.12

Excessive sleepiness and accidents. Insomnia isassociated with excessive sleepiness, which can impairfunctioning, in rotating shift workers compared withday workers.12 Studies have found a 12% frequency ofdrowsy driving and an increased risk of driving

accidents related to sleepiness in rotating shift workerswith SWD compared with those without the disorder.Relative risk of injuries and accidents increases witheach successive night shift worked.22 The effects ofshift work on patient and employee safety are animportant consideration in the health care field, wheremany workers have extended shifts.23

Productivity. Similarly, it is the combination of nightor rotating shift work and daytime sleepiness orinsomnia that decreases productivity, not each factoralone.12 Rotating shift workers with insomnia and/orexcessive sleepiness (SWD) missed significantly moredays of work (an average of 3 days per month over 3

months, a 10% decrease in productivity) than dayworkers with these symptoms, who missedapproximately half a day of work per month over the3-month period. This effect was not seen in shiftworkers who did not have insomnia or excessivesleepiness: they also missed a half day or less of workover 3 months.12 Rotating shift workers whoexperience both insomnia and excessive sleepiness areat the greatest risk for lost productivity. (See Keller23for a review of potential productivity problems inhealth care workers on extended shifts.)

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Shift work is very prevalent in oursociety. However, only a subset of shift

workers meet criteria for SWD and needtreatment. Potential targets for treatmentare (1) the persons work schedule, (2)difficulty sleeping during the day, and,most important, given the accident datadiscussed above, (3) difficultyfunctioning because of excessivesleepiness (eg, commuting home safely).

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Summary

Pregunta 1 de 4The Shift work disorder (SWD) is adisruption of sleep patterns affecting

A. All people who work night orrotating shifts

B. Primarily workers in naturalresources, con struction, andmaintenance occupations, such asfarmers, fishermen, andconstruction workers

C. Approximately 10% of all shift

workers

D. Shift workers with hypertensionor cardiovascular disease


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RICHARD D. SIMON,JR,MD

Shift Work Disorder:Clinical Assessment andTreatment Strategies

P l l f ll l l 8 PM
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Identifying CircadianRhythm Disturbances

The most important clue that a patient may have acircadian rhythm sleep disorder is an irregularsleep/wake schedule. It is not possible for people tochange their circadian rhythm by more than 24 hoursin any given day.1,2 Thus, if a persons sleep/wakeschedule varies by more than 24 hours between dayson and off work, this suggests that he or she may havecircadian rhythm problems. One of the best ways toidentify such problems is to ask, Do you havedifficulty falling asleep at bedtime (insomnia) anddifficulty waking up when you need or want to(hypersomnia)? If the patient says yes, this canindicate a delayed sleep phase syndrome (ie, theperson may be a night owl). Individuals with thissleep pattern often overuse the snooze button, hitting itrepeatedly. This pattern is frequently seen in teenagers.

People may also fall asleep very early, say at 8:00 PM(hypersomnia), and wake up long before they want to(eg, 3:00 AM). This sleep pattern reflects an advancedsleep phase syndrome, a pattern frequently seen in theelderly (AV 1).

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2 D fi d it t t l t th h t


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Taking a Sleep History

The first step in assessing for shift work disorder(SWD) is to take a thorough sleep history. The mostimportant item to ask about is the persons schedule ofwork and sleep. Ask the person how his or hersleep/wake schedule differs on work days, days off, andvacation days. (The persons sleep schedule when onvacation can give particularly helpful clues to thepersons intrinsic sleep/wake schedule.) (AV 2)

Assess the quality of sleep and wakefulness by asking

questions such as these:

! Do you sleep all night? Do you feel refreshedin the morning? Or do you have fragmented sleep?

! Do you find it easy to stay alert throughoutthe day? Or do you find yourself getting fatigued andsleepy?

! Do you snore? Has anyone you live withwitnessed any episodes when your breathing appeared

to stop and then start again while you were asleep(sleep apnea)?

Restless legs syndrome, characterized by anuncomfortable, creeping, crawling, restless feeling inthe legs, can make it very difficult to fall asleep. If theperson reports snoring or witnessed episodes of apnea,abnormal nocturnal behaviors (eg, injuring self orothers by acting out dreams), or symptoms suggestingnarcolepsy, a sleep study is required. It is alsoimportant to ask about use of drugs or medications tohelp with sleep or alertness (eg, caffeine in thedaytime, pills or alcohol to promote sleep) and thequality and safety of the sleeping and wakingenvironments. A medical and psychiatric history is

necessary to identify conditions that might becontributing to the sleep problems (eg, respiratoryproblems, pain, depression, anxiety).

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3 In some situations depression or anxiety scales or a


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Assessment Tools

The simplest and most important assessment tool forday-to-day clinical use by primary care physicians andgeneral psychiatrists is a sleep diary (AV 3).

Several easy-to-use scales are also commonly used insleep assessments. The Stanford Sleepiness Scale3andthe Epworth Sleepiness Scale4measure level ofexcessive sleepiness. The Epworth Sleepiness Scaleasks the person to rate the likelihood of dozing in 8different situations on a 4-point scale (0 = would never

doze to 3 = high chance of dozing), with a score of 10 orgreater suggesting the need for further evaluation. TheInsomnia Severity Index5assesses severity of currentsleep problems and their effect on daytime functioning.Scales such as these are particularly useful for trackingthe effectiveness of an intervention over time.

In some situations, depression or anxiety scales or ageneral outcome scale such as the Short-Form 36-ItemHealth Survey, Version 2,6may be useful.

Actigraphy, which uses a device worn on the wrist torecord motion (ie, suggesting the person is awake) is

not generally necessary in assessing for SWD, since anaccurate history and a sleep diary will usually supplyall necessary information. Referral for overnight sleepstudies or polysomnography is also not indicated todiagnose SWD, but is indicated if one suspects thepatient may have obstructive sleep apnea, parasomniasleading toinjurious nocturnal behaviors during sleep,

or narcolepsy. If narcolepsy is suspected in a shiftworker, it is usually necessary to have the workerdiscontinue shift work for 24 weeks, because shiftwork itself and the associated circadian misalignmentcan confuse testing for narcolepsy. Narcolepsy issuggested by a history of excessive sleepiness that oftenstarted when the person was a teenager and predates

his or her shift work.

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Differential Diagnosis andComorbid Conditions

Conditions that frequently occur in conjunction withSWD include obstructive sleep apneaand restlesslegs syndrome. Signs suggesting sleep apnea includelarge neck size, crowded oropharynx, and reports ofwitnessed apneas. Poor sleep habits of shift workerscan also cause them to develop learned insomniabehaviors, referred to as psychophysiologic insomnia.Other comorbid conditions include depressiveand/or anxiety disordersand chronic fatigue,which can be difficult to distinguish in a person with

chronic circadian dyssynchrony.

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5 Zeitgebers: Strategies for


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Treatment Goals

The primary goal of treatment for SWD is to reduce thedegree of circadian misalignment by fostering bettersleep when it is desired and improved alertness andfunctioning when appropriate. Other goals are toidentify and appropriately treat any intrinsic sleepdisorders (eg, apnea) and any medical or psychiatricdisorders that are present. Nonpharmacologicstrategies should be tried before considering use ofmedications to promote sleep and/or alertness.

Zeitgebers: Strategies forShifting the BiologicalClockThe term zeitgeber (German for time giver) describes

an external cue that helps synchronize a plant oranimals internal clock to the earths 24-hourlight/dark cycle.7The most powerful zeitgebersinhumans are light, supplemental melatonin, dark, andexercise.

Very bright light has powerful effects,1,2with

individuals being most sensitive to the effects of lightapproximately 2 hours before or 12 hours after theirspontaneous wake time. If a pulse of very bright light isgiven 24 hours before a persons spontaneous waketime (eg, 3:00 AM for someone with a usual wake timeof 6:00 AM), the person is likely to wake up 24 hourslater (ie, to move toward a delayed sleep phase,becoming more of a night owl). On the other hand, ifyou expose the person to very bright light at thespontaneous wake time or in the hour or so after, theperson is likely to wake up 24 hours earlier (ie, tomove toward an advanced sleep phase, becoming moreof a morning lark).

31

Melatonin acts in the opposite way.1,2When


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pp yadministered in the evening, it tends to make theperson fall asleep and wake up earlier (ie, to advancethe sleep phase). When administered in the morning, ittends to make the person stay up later and wake uplater (ie, to delay the sleep phase).

Dark also has powerful effects on sleep phase.1,2Thus,naps in a darkened environment act in much the sameway as melatonin. Greatly limiting exposure to light inthe evening will help you go to sleep earlier.Conversely, absence of light in the morning will helpyou sleep later. Because primarily the shorter

wavelengths (eg, blue light) lead to phase shifts, onestrategy for exposing the biological clock to dark is towear dark or blue-blocking sunglasses.

Similar phase response curves have been found forexercise.1,2Exercising in the early evening tends tophase-advance you and make you more of a morningperson. Exercising after midnight generally does the

opposite. However, exercise is not often used to adjustsleep phase in humans (AV 4).

32

6 significant others in the shift workers family and


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Practical Strategies forSleep Problems AssociatedWith Shift Work

To minimize problems associated with shift work,workers should have as predictable a work schedule aspossible. It is also helpful if employers providesufficient breaks at work, allow shift workers to take ashort nap at work, avoid schedules that involveworking multiple days in a row, and provide sufficienttime off between work days. These strategies areimportant because the vast majority of shift workers donot fully entrain (ie, their biological clocks never fullysynchronize with their required work and sleep

schedules). It is also useful to try to limit commutingtime and overtime.

Another key strategy is to minimize circadianmisalignment between work days and days off, whichinvolves educating and enlisting the support of

g yimmediate social circle. For most shift workers, thismeans producing a phase delay in their biologicalclocks (ie, to make them more night owls). This isdone by changing the persons environment so that heor she gets as much light as possible during the

scheduled day and as little light as possible duringthe scheduled night and by minimizing the differencein sleep/wake patterns between work days and daysoff. Practically, this means having bright light at work,wearing dark glasses during the drive home when oneis likely to be exposed to light, and keeping thebedroom, bathroom, and other rooms that will be used

at home as dark as possible during the desired sleepperiod.

Shift workers who achieve complete or even partialentrainment (ie, their biological clocks becomerealigned with a new sleep/wake schedule) showmarked improvements in psychomotor vigilance,memory, reaction time, night work performance, andmood and reductions in fatigue, excessive sleepiness,and mental exhaustion compared with those who donot8,9 (AV 5).

33


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34

Summary


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SWD needs to be considered in allpatients who have a sleep/wake schedulethat differs by more than 24 hours on

work days compared with days off andwho exhibit symptoms of sleepiness at

work and difficulty sleeping during thedesired sleep time. Asking about snoringand restless legs symptoms can lead tocomorbid diagnoses that, if treated, canimprove the shift workers sleep.

xxxv

SummaryPregunta 1 de 4The most important clue that a patient mayhave a circadian rhythm sleep disorder is:

A. Complaint of restless legssyndrome

B. An irregular sleep/wake schedule

C. Depression

D. Sleep apne

4


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Cases

1 mass index (BMI) of 26. His mother and brother both


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The young man withdifficulty falling asleepA 24-year-old male patient reports difficulty fallingasleep, followed by daytime sleepiness, a pattern thathas persisted for about 5 years since his days as astudent. His excessive sleepiness has become moresevere during the past year due to the 8 AM startingtime for his work shift. He recently needed to take 2personal days off from work due to inability to reporton time. Once asleep, he does not have difficultystaying asleep. His bedtime ranges from 11:30 PM to1:00 AM, with time required to fall asleep averaging 2hours. His wake time is scheduled for 6:45 AM onworkdays. Weekday mornings are particularly difficult.The patient feels "out of it" until about noon. He hasfallen asleep while driving to work and has had severalnear-miss traffic accidents the past month.

The patient is being treated with sertraline 50 mg fordepression, which was first diagnosed 2 years ago, andwith zolpidem 10 mg as needed for insomnia. Hesuffers from exercise-induced asthma. His bloodpressure is stable at 130/80 mm Hg, and he has a body

suffer from similar types of insomnia symptoms.Physical and neurological exams were normal. He hada score of 12 on an ESSquestionnaire.

37

Which of the following additional assessmentswould you next employ for this patient?

A. PolysomnogramB. Actigraphy

C. Sleep diary

D. Multiple sleep latency test

Like the ESS, a sleep diary is a first-line diagnostic toolf d l di d b f i f

environmental factors involved in a clinical sleepdi d h d l i i I h


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for suspected sleep disorders because of its ease ofadministration and low cost. A sleep diary will plot thepatient's sleep pattern and is suitable as the next test inthis case.Actigraphymay be used but is notcommonly available in primary care practices.

Polysomnograms and multiple sleep latency tests aremore elaborate diagnostic methods reserved forvalidation of initial screening tests, or to evaluate forother sleep disorders, such as OSA and narcolepsy.

Circadian rhythm sleep disorders are disorders of sleepand wake timing. Thus, an essential aspect of

diagnosing and treating circadian rhythm sleepdisorders is to determine whether symptoms are due tochronic or short-term misalignment of the patient'scircadian rhythms with external 24-hour cues, or dueto other etiologies. A sleep diary is an easilyadministered diagnostic tool that can be easily used ina primary care setting to determine if the patient'sinternal circadian sleep and wake rhythm is misalignedwith work or social schedules.

The pathophysiology of circadian rhythm sleepdisorders is multifactorial, only partially understood.What is of importance to clinicians is that theyconsider the full range of physiological, behavioral, and

disorder when developing treatment strategies. In thecase of Circadian rhythm sleep disorders, their etiologycan be intrinsic due to endogenous factors, or extrinsicdue to factors in the environment.

ASSESSMENTThe patient completed a 7-day sleep diary during hisnormal work week (see the Figure). The diary confirmsa bedtime of 10:30-11:45 PM on workdays and aprolonged time to fall asleep of over 2 hours. Onweekends, bedtimes are later (midnight to 1 AM), but itstill takes 1-2 hours to fall asleep. Note that on

38

Saturday, he sleeps in until 11 AM, and on Thursday, het k i th ft b t t PM


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took a nap in the afternoon between 3 to 4 PM.Average sleep duration is less than 6 hours onweekdays. The patient went on vacation for a 10-dayperiod shortly after his initial visit, providing anopportunity for actigraphy monitoring during his

preferred sleep schedule. Actigraphy showed anaverage bedtime of 3-4 AM and an average wake timeof 10 AM to noon while on vacation. After returningfrom vacation, the patient said he had been able tocatch up on his sleep and feels much better. However,after returning to work, he reports that his bedtimeinsomnia has returned, often preventing him from

falling asleep before 2 AM.

39

Pregunta 1 de 2Based on the previous description, what isthe most suitable diagnosis for the patientin case 1?

A. Psychophysiologic (conditioned)insomnia

B. Insomnia due to depression

C. Advanced sleep-phase disorder

D. Delayed sleep-phase disorder

The patient's symptoms are consistent with delayedsleep phase disorder namely a stable pattern of delay

alerting effect, which can facilitate waking.Pharmacologic therapies such as hypnotic agents or


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sleep-phase disorder, namely a stable pattern of delayin the nighttime sleep period until the early morninghours followed by inability to wake up until the latemorning. In contrast, patients with insomnia disorder,including psychophysiologic insomnia or insomnia

associated with depression, do not typically show astable pattern of delayed sleep and when allowed tosleep at a later time have normal sleep duration.Advanced sleep-phase disorder is characterized byearly sleep onset and premature awakening, theopposite of delayed sleep-phase disorder.

Treatment should be aimed at advancing the timing ofsleep and wake cycle. Morning bright light exposure(close to natural awakening) signals the circadian clockto advance its timing. Similarly, low-dose melatoningiven in the late afternoon or early evening signals theclock to advance. (Melatonin is not approved by theFDA for the treatment of circadian rhythm sleepdisorder.) One should avoid bright light exposure inthe evening because it will delay or shift circadianrhythms. An advance in the timing of circadianrhythms (advance shift) will result in earlier sleeponset and awakening, which is needed to synchronizewith the desired sleep/wake and work schedule. Inaddition, bright light in the morning can have an

Pharmacologic therapies such as hypnotic agents orantidepressants to treat symptoms of insomnia withoutresetting the circadian clock will only partially addresssymptoms, rather than the underlying cause of thesymptoms.

40

DIAGNOSIS

The patient's histo confi ms that his abilit to


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The patient's history confirms that his ability toperform on the job is impaired by his excessivesleepiness and lack of energy and alertness in the workplace. He thinks that his occasional feelings ofdepression and anxiety are associated with poor sleep.

Although he is concerned about poor performanceassociated with his sleep pattern, he does not feelanxious overall. "I'm just never sleepy at 10:30 atnight," he says. He is diagnosed with delayedsleep-phase disorder. According to the InternationalClassification of Diseases, 10th Revision (ICD-10),diagnostic billing codes for Circadian rhythm sleep

disorders start with G47.2, with delayed sleep-phasedisorder G47.21.

41

Episodic andparoxysmal

disorders G40-G47

Sleepdisorders G47

Circadianrhythm sleep

disorder G47.2

delayed sleepphase type

G47.21

INITIAL TREATMENT

The patient was instructed to purchase a bright light


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The patient was instructed to purchase a bright lightbox, readily available on the Internet, and sit in front ofthe light source (1-2 feet away) for 1 hour in themorning, starting at 10:30 AM on a weekend day (offwork). Light box exposure was then advanced by 1 hour

each morning until he started treatment at his normalworkday wake up time of 6:30 AM. He was alsoinstructed to take melatonin 1 mg at 8 PM for the next3 weeks.

Recognizing the pattern of the patient's sleep-wakecycle is the key to both the diagnosis and treatment of

circadian rhythm sleep disorders. The goal of circadianrhythm sleep disorder is to synchronize (entrain) thesleep-wake cycle with the appropriate external physicalenvironment and work schedule. Treating symptoms ofinsomnia or excessive sleepiness without resetting thecircadian rhythm sleep disorder patient's circadianclock will only partially address the symptoms, ratherthan the underlying cause of the symptoms. Thus, theprincipal goal of therapy for the delayed sleep-phasedisorder patient (as illustrated in case 1) is to advancethe timing of circadian rhythms. Conversely, the goal oftherapy for an advanced sleep-phase disorder patientwould be to delay the timing of circadian rhythms.

42

What is the principal goal in managing thesleep disorder for this case?

A. Advance the timing of the patient'scircadian rhythms

B. Increase the duration of sleep

C. Provide treatment with the use ofprescription drugs

D. Avoid sleeping so late on weekends

FOLLOW-UP

The patient reported good compliance with nightly


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The patient reported good compliance with nightlyMLT treatment but could tolerate morning lighttherapy for only 30-40 minutes on some days. Hereports a bedtime of 11 PM, falling asleep by midnighton most days. He is able to awaken with the aid of an

alarm clock at 6:30 AM on workdays, but feels like hecould sleep longer. He wakes up naturally at 8-10 AMon weekends.

43

2

Th ld ith hi tatorvastatin. The patient has a paternal family historyof early risers. His wife has informed him that he


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The old man with a historyof difficulty staying asleep

PRESENTATION AND PATIENT HISTORY

A 66-year-old man has a history of difficulty stayingasleep. This has caused him to be a habitual early riseraround 5 AM virtually every day for about 10 years. Hisdifficulty in staying asleep has become progressivelyworse. His typical sleep pattern is to fall asleep on thecouch by 7 PM, wake up 90 minutes to 2 hours later,and then go to bed around 9:30-10 PM. He usuallysleeps until 3-4 AM or until he goes to the bathroom,after which he has difficulty going back to sleep. Heoften lays awake in bed for up to 2 hours until he risesat 5-5:30 AM. By the afternoon and early evening, he isexcessively sleepy and struggles not to fall asleep. Hereports that his ES has affected his social life andrelationship with his wife due to his drowsiness. He

says his ideal sleep schedule would be to fall asleepabout 10 PM and wake at 5-6 AM. His score on an ESSquestionnaire is 12.

He has a history of hypertension and hyperlipidemia,for which he is treated with olmesartan and

of early risers. His wife has informed him that hesnores lightly but has not witnessed any breathingirregularities during his sleep. He has no restless legssymptoms and is not depressive, but he is frustrated byhis sleep problem. He has reflux symptoms when he

eats late. His physical examination, cognition, andmental health status are normal.

44

What is the most likely diagnosis for the patientin this case?

A. Advanced sleep-phase disorder

B. Delayed sleep-phase disorder

C. Irregular sleep-wake pattern

D. Insomnia due to nocturia

The patient's symptoms are consistent with advancedsleep-phase disorder, a stable pattern of sleep onset

Schematic of typical sleep phase vs 4 circadian rhythmsleep disorders. A feature of ASPD, DSPD, and


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p p , p pseveral hours earlier than the usual nighttime sleepperiod and sleep offset several hours before the normalor desired wake time. Advanced sleep-phase disorder ismore common in older adults. Nighttime urination

typically occurs in men of the patient's age but is notthe primary cause of an advanced sleep-wake cycle ordaytime sleepiness in this case.

p , ,non-24-hour sleep pattern is that the sleep architectureand total amount of sleep are comparable to thenormal pattern, but timing of sleep does not conformto a conventional 24-hour schedule.

45


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46


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47

ASSESSMENT

The patient returns 3 weeks later and provides a 7-day


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sleep diary (Figure). The diary shows that he laysawake for 1-2 hours before getting out of bed at 5-5:30in the morning. The premature wake times arepreceded by involuntary drowsiness and napping in the

early evening from 5:30-8 PM. His symptoms supporta diagnosis of Advanced sleep-phase disorder.

48

Which treatment is most appropriate for

this patient?

A. An antidepressant

B. A stimulant

C. Melatonin

D. Light therapy

Timed light exposure for 1-2 hours in the evening (7-9PM) is indicated as standard first-line therapy to delay


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onset of the sleep cycle in cases of advancedsleep-phase disorder. In addition, the patient iscounseled on sleep hygiene and told to avoid napsbefore a targeted bedtime of 10:30 PM. Physical

activity such as walking before or after dinner isrecommended to maintain wakefulness during theevening. Low-dose Melatonin taken in the morningmay be useful but may induce residual sleepiness. Thepatient does not suffer from mood disorders, soantidepressant medication is not indicated. Stimulantshave a limited role in treating advanced sleep-phase

disorder. Caffeine taken in moderation is acceptablefor maintaining wakefulness but is not considered aprimary therapy for advanced sleep-phase disorder.The wake-promoting agents modafinil and armodafinilare approved for short-term use in treating excessivesleepiness associated with sleep apnea, narcolepsy, andshift-work disorder, but not advanced sleep-phase

disorder.

49

Actigraphy


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Consiste en un pequeo aparato que se coloca en la mueca del individuo yregistra sus movimientos a lo largo de la noche. Los datos obtenidos seanalizan mediante un sistema computarizado que permite acumular datoshasta un mximo de 22 das consecutivos, y estimar diversos parmetros delsueo (Hauri & Wisbey, 1992). Contrariamente a la polisomnografa, laactigrafa de mueca no es un instrumento costoso ni intrusivo y suutilizacin es sencilla. Permite registrar periodos de 24 horas y proporcionainformacin del ritmo circadiano. No obstante, slo mide vigilia y sueo y noestadios especficos de sueo.

Trminos del glosario relacionados

ndice

Captulo 4 - The young man with difficulty falling asleep

Arrastrar trminos relacionados aqu

Chronic fatigue

El Sndrome de Fatiga Crnica (SFC) es una enfermedad grave compleja y debilitante


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g ( ) g p j y

caracterizada por una fatiga intensa, fsica y mental, que no remite, de forma

significativa, tras el reposo y que empeora con actividad fsica o mental. La aparicin

de la enfermedad obliga a reducir sustancialmente la actividad y esta reduccin de

actividad se produce en todas las Actividades de la Vida Diaria (AVD).

El impacto del SFC en la vida del enfermo es demoledor, tanto por la enfermedad en s

misma como por el aislamiento e incomprensin del entorno, de hecho, las medidas

validadas de calidad de vida, cuando se comparan con otras enfermedades, evidencian

que el SFC es una de las enfermedades que peor calidad de vida lleva aparejada.

Adems de estas caractersticas bsicas, algunos pacientes de Sndrome de Fatiga

Crnica (SFC) padecen diversos sntomas inespecficos, como debilidad muy especial

en las piernas, dolores musculares y articulares, deterioro de la memoria o la

concentracin, intolerancia a los olores, insomnio y una muy lenta recuperacin, de

forma que la fatiga persiste ms de veinticuatro horas despus de un esfuerzo.

Casi siempre la enfermedad es crnica (curaciones inferiores al 5-10%) y de un granimpacto en la vida del enfermo. De hecho, la mejor medida del impacto de la

enfermedad es evaluar las actividades previas y posteriores a la instauracin de la

enfermedad, tanto en la esfera fsica, como en la intelectual, aunque disponemos de

escalas validadas de Clasificacin de la Severidad e Impacto de la Fatigabilidad

Anormal en un paciente concreto, como por ejemplo la Escala IFR de Fatigabilidad

Anormal.


ndice

Captulo 3 - Differential Diagnosis and Comorbid Conditions


Circadian rhythm

Los ritmos biolgicos endgenos pueden ser de diferentes frecuencias [Adn; 1995,

Goldbeter; 2008,Haus; 2009,Ohdo; 2010,Smolensky et al; 2007,Valds-Rodrguez;

l l ]


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2009,Volpato et al; 2005]:

Ritmos de frecuencia alta (con periodos cortos menores a 30 minutos): - Ritmos con periodos de un milisegundo a 10 segundos de duracin, como el de la

actividad elctrica cortical.

- Ritmos con periodos de segundos de duracin, como el cardaco y respiratorio.

- Ritmos con periodos de 30 segundos a 20 minutos de duracin, como las oscilaciones

bioqumicas.

Ritmos de frecuencia media (con periodos intermedios desde media horahasta 6 das de duracin):

- Ritmos ultradianos, ciclos de media hora a 20 horas de duracin, como los ritmos

hormonales, las fases del sueo, la depresin pospandrial o post-lunch. - Ritmos circadianos o nictamerales, con periodos alrededor de 24 horas de duracin

(24 4 horas), producidos por la rotacin terrestre y que determinan los ciclos del da

y la noche (luz-oscuridad) fundamentales para regular la temperatura corporal, la

secrecin de cortisol y melatonina, el ciclo de vigilia-sueo, etc. - Ritmos dianos, con periodos de 24 2 horas de duracin.

- Ritmos infradianos, con periodos de 28 horas a 6 das de duracin, como los procesos

metablicos.

Ritmos de frecuencia baja (con periodos largos de ms de 6 das de

duracin):

- Ritmos circaseptanos, con periodos de 7 3 das de duracin, como el del bienestar

subjetivo.

- Ritmos circadiseptanos, con periodos de 14 3 das de duracin.

- Ritmos circavigintanos, con periodos de 21 3 das de duracin.

- Ritmos circatrigintanos o circamensuales, con periodos de unos 30 das de duracin

(30 5 das), definidos por el ciclo lunar de traslacin lunar y que determinan la

alternancia de las mareas y la luminosidad del cielo nocturno. - Ritmos circanuales o estacionales, con periodos de aproximadamente 1 ao de

duracin (1 ao 2 meses), definidos por el ciclo solar de traslacin terrestre y que

determinan las estaciones del ao, con sus diferencias en intensidad de luz y

temperatura y regulan la reproduccin e hibernacin animal.

- Ritmos de aos de duracin, como en ecologa y epidemiologa.

De todos ellos los ms estudiados son los circadianos y los estacionales.


ndice

Captulo 1 - Properties of the Circadian Rhythm


Circadian rhythm sleep disorders

LOS TRASTORNOS DEL SUEO POR ALTERACIN DEL RITMO CIRCADIANOAnte situaciones extremas para el individuo se pierde la periodicidad circadianade


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Ante situaciones extremas para el individuo se pierde la periodicidad circadiana deaproximadamente 24 horas, (como en el turno laboral nocturno, enfermedades

intercurrentes, etc.). Hay una interrupcin transitoria del funcionamiento del NSQ ypierde el control de los osciladores perifricos. [Haus;2009,www.sleepassociation.org]. Es lo que ocurre en los TSRC en los que laperturbacin del patrn de sueo es consecuencia de la desincronizacin entre el ritmode vigilia-sueo deseado (por las circunstancias del entorno del individuo) y su propioritmo vigilia-sueo circadiano marcado por el marcapasos interno o reloj biolgico

[Barion et al; 2007,Haus et al; 2006,Lu et al; 2006, Martinez et al; 2010]. Lasrepercusiones que tendrn en estas personas (hasta que se adapte su ritmo) sernalteraciones del sueo (insomnio de conciliacin y mantenimiento y excesivasomnolencia diurna [Lu et al; 2006]), biolgicas a nivel celular y molecular, cambiosen la actividad cerebral, alteraciones funcionales y del metabolismo de lpidos ycarbohidratos, cambios en la resistencia a la insulina, cambios hormonales-endocrinos(secrecin de hormona de crecimiento, melatonina, etc.), etc. [Haus et al;

2006,www.sleepassociation.org].

Los TSRC segn la segunda edicin de la Clasificacin Internacional de los Trastornosdel Sueo [Westchester; 2005] de la Academia Americana de Medicina del Sueo

(American Academy of Sleep Medicine o AASM) pueden ser primarios, por malfuncionamiento del reloj biolgico, (Sndromes del retraso y adelanto de fase, Patrnirregular del ciclo vigilia-sueo y Sndrome de ciclo vigilia-sueo diferente a 24 horas);secundarios, en los que son las circunstancias del medio ambiente las que provocan eldesfase del reloj biolgico, (Jet lag, TSRC secundario al trabajo a turnos, TSRCsecundario a enfermedades y al consumo de frmacos u otras sustancias) y otros TSRCno especificados [Martinez et al; 2010].


ndice

Captulo 2 - Circadian Rhythm Sleep Disorders


Delayed or advanced sleep phases

Sndrome de la fase del sueo retrasada. Se caracteriza, como su propio nombre


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Sndrome de la fase del sueo retrasada. Se caracteriza, como su propio nombre

indica, por un retraso habitualmente mayor de dos horas en los tiempos de

conciliacin del sueo y despertar, en relacin con los horarios convencionales osocialmente aceptados. Los individuos afectados por esta entidad tienen una prctica

imposibilidad para dormirse y despertarse a una hora razonable, hacindolo ms tarde

de lo habitual. La estructura del sueo es normal, destacando nicamente en losestudios polisomnogrficos un importante alargamiento de la latencia del sueo o el

tiempo que tardan en dormirse los pacientes. Estos tienen con frecuencia problemas

socio-laborales, ya que sus horas de mayor actividad suelen ser las de la noche. Enestos individuos estn tambin retrasados otros ciclos biolgicos circadianos, como

son el de la temperatura y el de la secrecin de melatonina.

Sndrome de la fase del sueo adelantada.Es menos frecuente que el sndromede la fase retrasada. Los periodos de conciliacin del sueo y de despertar son muy

tempranos o precoces con respecto a los horarios normales o deseados. Los sujetos que

padecen este sndrome suelen quejarse de somnolencia durante la tarde y tienentendencia a acostarse muy pronto, y se despiertan espontneamente tambin muy

pronto por la maana. Cuando se acuestan muy tarde, por factores exgenos, sufrenun dficit de sueo, ya que su ritmo circadiano les despierta igualmente pronto. No se

conoce su prevalencia, pero se estima en torno al 1% en los adultos y ancianos, y

aumenta con la edad (probablemente porque con la edad se acorta el ritmocircadiano). Afecta a ambos sexos por igual.


ndice



Endogenous rhythmicity


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La periodicidad circadiana, como la del ritmo vigilia-sueo, est mediada

genticamente, tiene un control y est sincronizada al ciclo regular de 24 horas de

luz-oscuridad ambiental por los osciladores internos, y por ltimo est modulada por

influencias ambientales que permiten su adaptacin a las condiciones variables del

entorno [Adn; 2004,Aschoff; 1967,Chiesa et al; 1999, Haus et al; 2006]:


ndice

Captulo 1 - Properties of the Circadian Rhythm


Escala de Somnolencia de Epworth

La Escala de Somnolencia de Epworth (Johns 1991) estima la somnolencia


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La Escala de Somnolencia de Epworth (Johns, 1991) estima la somnolenciasubjetiva diurna de individuos adultos. La escala de ocho tems, pide alindividuo que punte de 0 a 3 el grado de somnolencia en diferentessituaciones cotidianas, diferenciando somnolencia de fatiga. Actualmente,un puntaje de 10 o ms se considera como el punto de corte ms

apropiado para detectar somnolencia patolgica. La Escala deSomnolencia de Epworth es sencilla de administrar, es actualmente lamedida subjetiva de somnolencia diurna ms corrientemente empleada.Chung (2000) en su estudio encontr que la escala resultaba ser uninstrumento til para diferenciar pacientes con y sin un grado patolgico desomnolencia objetiva diurna. Tambin Sanford, Lichstein, Durrence, Riedel,Taylor & Bush (2006) detectaron que los sujetos con insomnio obtienenpuntuaciones ms elevadas en la Escala de Somnolencia de Epworth que los

sujetos sin insomnio, lo que puede ayudar a discriminar sujetos con eltrastorno de aquellos sin el mismo. La escala ha sido traducida al alemn yespaol y se ha encontrado que su uso no resulta afectado por factoresculturales o de lenguaje (Chung, 2000; Izquierdo-Vicario, Ramos-Platn,Conesa-Peraleja & Lozano-Parra, 1997).


ndice

Captulo 4 - The young man with difficulty falling asleep

Captulo 4 - The young man with difficulty falling asleepCaptulo 4 - The old man with a history of difficulty staying asleep


Genetic control

l l l d l i ( b jid if i ) l i i d l


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En las clulas del organismo (en cerebro y tejidos perifricos), el mantenimiento de la

ritmicidad circadiana depende de algunos genes que hay en su ncleo, genes del reloj

o genes circadianos, que componen la maquinaria molecular del reloj circadiano

[Haus; 2009,Hofman et al; 2005]. Se expresan mediados por seales humorales y

neuronales, como la melatonina, que parten de los osciladores internos [Haus et al;2006,Hofman et al; 2005]. Las lneas de investigacin gentica han tratado de identificar los polimorfismos y

mutaciones que sufren estos genes y se asocian al cronotipo de una persona (medido

por el Cuestionario de matutinidad-vespertinidad de Horne y stberg), determinados

TSRC en algunas familias, adicciones (a drogas y alcohol) y otras enfermedades

(diabetes, enfermedades cardiovasculares, cncer, etc.) [Bechtold et al; 2010,Eismann

et al; 2010,Rosenwasser; 2010,Sack et al; 2007b].


ndice

Captulo 1 - Genetics of the Circadian Rhythm


Obstructive sleep apnea

El d d hi b t ti d l (SAHOS) f d d


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El sndrome de apnea e hipopnea obstructiva del sueo (SAHOS) es una enfermedad

frecuente que afecta al 4% de la poblacin adulta. Su sntoma cardinal es la

somnolencia diurna excesiva que, junto a la alteracin del nimo y deterioro cognitivo,

producen un deterioro progresivo en la calidad de vida de los pacientes. Adems, se ha

asociado a mayor riesgo de hipertensin arterial, morbimortalidad cardiovascular,accidentes laborales y de trnsito. Esta entidad est ostensiblemente subdiagnosticada,

por lo que es necesario mejorar su conocimiento para aumentar la pesquisa para su

adecuado tratamiento.


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Restless legs syndrome

Corresponde a un trastorno del mo imiento caracteri ado por la presencia de


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Corresponde a un trastorno del movimiento caracterizado por la presencia de

sensaciones desagradables localizadas en extremidades inferiores que llevan a la

imperiosa necesidad de moverlas. Esta sensacin empeora con el reposo e interfiere

con el sueo.La prevalencia de este sndrome es variable segn los estudios y va de 10,6% en USA, y11,6% en Espaa con una mayor proporcin de mujeres versus hombres de 3:1. La

prevalencia va aumentando con la edad, incluso los primeros sntomas pueden

aparecer en la infancia.


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Shift work disorder

Trastorno del sueo por alteracin del ritmo circadiano (TSRC) de Tipo trabajo a


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Trastorno del sueo por alteracin del ritmo circadiano (TSRC) de Tipo trabajo a

turnos segn la segunda edicin de la Clasificacin Internacional de los Trastornos del

Sueo (ICSD-2 [Westchester; 2005]) de la Academia Americana de Medicina del

Sueo, o Trastorno del sueo por horarios cambiantes de trabajo.

Este TSRC se produce cuando el horario laboral se solapa con el periodo de sueohabitual para el trabajador y no consigue adaptar su ritmo biolgico a este horario de

vigilia-sueo que, debido a sus circunstancias laborales, debe seguir [Lu et al; 2006,

Martinez et al; 2010,Waage et al; 2009]. Puede darse en trabajos con guardias nocturnas ocasionales, turnos rotatorios, horario

fijo nocturno y aquellos que empiezan muy temprano por las maanas (antes de las 6

a.m.) [Barion et al; 2007,Sack et al; 2007].


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Zeitgebers

The four most important time givers:


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! The light(and thus the rising hour) controls the melatonin secretion. It isproven that the exposure to light has an arousing effect and an influence on the sleeprhythms. Phototherapy has shown its efficiency in a large number of pathologies(insomnia, depression, fibromyalgia...).

! Physical exercicehas a significant influence on the body temperature. Thewarmer the organism was during the day, the stronger becomes the action ofmelatonin on the fall of body temperature in the evening. Endurance sports (walking,

jogging, swimming, ski...) are traditionally associated with a deeper sleep.(Cf.) On theopposite, it is not advised to practice an intensive sport less than three hours beforegoing to sleep.Be careful, that advice for insomniacs must not lead the sick people to stop all activitytoo early in the evening, like some bad sleepers do who "wait for the train of sleep"from 9 PM on and hope to find sleep in trying not to do anything.

! The meal hoursinfluence the brain through hormones that have beendiscovered quite recently like the hypocretin/orexin (which has a common action inthe food intake behaviors and the circuits of sleep).

! Social contacts, love, laughter and pleasure also play a role that is not tobe neglected in the synchronization of the sleep rythms.These new "somnications" are rarely the subject of specific scientific studies but someobservations suggest their importance.In 1532, Rabelais already asserted very opportunely that "The cheerful always recover"The pleasures of life are often associated with a short and efficient sleep whereas"clinophilia" (the need to lie down), in which the tired subjects seek shelter, prolongesthe sleep duration but diminishes the slow wave activity, thus making the sensation oftiredness even worse. (Cf. "hypo-sleep syndrome) Besides, it is known that (like incases of forced bed rest), the sudden decrease of activity induces sleep disturbances

and functional disorders very quickly.


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Captulo 3 - Sin ttulo


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How the Circadian Rhythm Affects Sleep, Wakefulness, And Overall Health