Attention-Deficit Hyperactivity Disorder

ByChris Golner

April 19, 1999Biochemistry/Molecular Biology Seminar

ADHD Statistics

3-5% of all U.S. school-age children are estimated to have this disorder.

5-10% of the entire U.S. populationMales are 3 to 6 times more likely to have

ADHD than are females.At least 50% of ADHD sufferers have

another diagnosable mental disorder.

OutlineHistory of ADHDSymptoms and Diagnosis: DSM-IV criteriaPossible causesTreatments

Stimulants

Outcome

History of ADHDMid-1800s: Minimal Brain DamageMid 1900s: Minimal Brain Dysfunction1960s: Hyperkinesia1980: Attention-Deficit Disorder

With or Without Hyperactivity

1987: Attention Deficit Hyperactivity Disorder1994-present: ADHD

Primarily Inattentive Primarily Hyperactive Combined Type

Diagnosing ADHD: DSM-IV

Inattentiveness:

Has a minimum of 6 symptoms regularly for the past six months.

Symptoms are present at abnormal levels for stage of development

Lacks attention to detail; makes careless mistakes

has difficulty sustaining attention

doesn’t seem to listen fails to follow through/fails

to finish projects has difficulty organizing

tasks avoids tasks requiring

mental effort often loses items necessary

for completing a task easily distracted is forgetful in daily activities

Diagnosing ADHD: DSM-IV

Hyperactivity/ Impulsivity:

Fidgets or squirms excessively

leaves seat when inappropriate

runs about/climbs extensively when inappropriate

has difficulty playing quietly

often “on the go” or “driven by a motor”

talks excessively blurts out answers before

question is finished cannot await turn interrupts or intrudes on

others

Has a minimum of 6 symptoms regularly for the past six months.

Symptoms are present at abnormal levels for stage of development

Diagnosing ADHD: DSM-IV

Additional Criteria:

Symptoms causing impairment present before age 7

Impairment from symptoms occurs in two or more settings

Clear evidence of significant impairment (social, academic, etc.)

Symptoms not better accounted for by another mental disorder

Problems of Diagnosis

Subjectivity of CriteriaInconsistent evaluations--presence of

symptoms usually given by teacher or parentStudy by Szatmari et al (1989) showed that the

number of diagnosed cases of ADHD decreased 80% when observations of parent, teacher and physician were used rather than just one source

Symptoms in females more subtle---leads to underdiagnosis

ADHD and the BrainDiminished arousal of

the Nervous SystemDecreased blood flow

to prefrontal cortex and pathways connecting to limbic system (caudate nucleus and striatum)

PET scan shows decreased glucose metabolism throughout brain

Comparison of normal brain (left) and brain of ADHD patient.

ADHD and the Brain IISimilarities of ADHD symptoms to those from

injuries and lesions of frontal lobe and prefrontal cortex

MRIs of ADHD patients show:Smaller anterior right frontal lobe

abnormal development in the frontal and striatal regionsSignificantly smaller splenium of corpus callosum

decreased communication and processing of information between hemispheres

Smaller caudate nucleus

What causes ADHD?Underlying cause of these differences is still

unknown; there is much conflicting data between studies

Strong evidence of genetic componentPredominant theory: Catecholamine

neurotransmitter dysfunction or imbalance decreased dopamine and/or norepinephrine

uptake in brain theory supported by positive response to

stimulant treatment Recent study indicates possible lack of serotonin

as a factor in mice

Scientific AmericanHttp//www.sciam.com/1998/0998issue/0998barkely.html#link1

Dopamine in the Brain

Genetic Linkages to ADHDTwin studies by Stevenson, Levy et al, and

Sherman et al indicate an average heritability factor of .80

Biederman et al reported a 57% risk to offspring if one parent has ADHD.

Dopamine genesDA type 2 geneDA transporter gene (DAT1)Dopamine receptor (DRD4, “repeater gene”) is

over-represented in ADHD patients

DRD4

DRD4 is most likely contributorDRD4 affects the post-synaptic sensitivity in

the prefrontal and frontal cortexThis region of cortex affects executive

functions and attentionExecutive functions include working

memory, internalization of speech, emotions, motivation, and learning of behavior

TreatmentCounseling of individual and familyStimulants Tricyclic antidepressantsBupropion Clonidine

StimulantsExact mechanism unknownRaise activity level of the CNS by decreasing

fluctuations of activity or lowering threshold needed for arousal

Similar in structure to NE and DA, and may mimic their actions

At least 75% have positive response with single dose

95% respond well to stimulant treatmentInclude methylphenidate, dextroamphetamine

and pemoline

Methylphenidate Is a piperidine

derivative commonly known as Ritalin®

Is believed to act as dopamine agonist in synaptic cleft

Stimulates frontal-striatal regions

Dosage (5-20 mg) must be adjusted to each patient

Taken orally, 2-3 times a day as needed

Behavioral effects start within 1/2 hour to hour after ingestion, peaking at 1 and 3 hours

Also comes in Sustained-Release form, whose effects last approximately twice as long.

Effects of MPH

Elevates moodRaises arousal of CNS and cerebral blood

flowIncreases productivityImproves social interactionsIncreases heart rate and blood pressureHas little or no abuse potential

Side Effects Common:

decreased appetiteinsomniabehavioral

reboundhead and stomach

aches

Also thought to cause temporary height and weight suppression

Mild:anxiety/ depressionirritability

Rare:tics (Tourette’s

Syndrome)overfocussingliver problems or

rash (Pemoline only)

OutcomeADHD can persist into adulthood, but usually

symptoms gradually diminishWhen it persists into adulthood, it usually requires

ongoing treatment and counselingmost will develop another disorder (especially

learning disability, ODD, depression, and/or conduct disorder)

Without treatment:antisocial and deviant behaviorincreased rates of divorce, moving violations,

incarceration, and institutionalization

ReferencesBarkley, R. Attention-Deficit Hyperactivity Disorder, 2nd Ed. New York: Guilford Press. 1998.

628 pp.

Shaywitz, B. and Shaywitz, S. Attention Deficit Disorder Comes of Age: Toward the 21st Century. Austin, TX: Hammill Foundation. 1992. 366 pp.

Rie, H.E. and Rie, E.D., Eds. Handbook of Minimal Brain Dysfunctions: A Critical View. New York: John Wiley & Sons. 1980. 744 pp.

Faigel, H. Attention Deficit Disorder: A Review. J. of Adolesc. Health, Mar 1995 Vol. 16: 174-84.

Cantwell, D.P. Attention Deficit Disorder: A Review of the Past Ten Years. J. of the Am. Acad. Of Child Adolesc. Psychiatry. 1996, Vol 35: 978-87.

Seideman, L., Biederman, J., and Faraone, S.V. A Pilot Study of Neuropsychological Function in Girls with ADHD. J. of Am. Acad. of Child Adolesc. Psychiatry, 1997. Vol. 36: 366-73.

Seideman, L., Biederman, J., and Faraone, S.V. A Pilot Study of Neuropsychological Function in Girls with ADHD. J. of Am. Acad. of Child Adolesc. Psychiatry, 1997. Vol. 36: 366-73.

ReferencesLevy, F., Hay D.A., McStephen, M., Wood, C., and Waldman, I. Attention-Deficit Hyperactivity

Disorder: A Category or Continuum? Genetic Analysis of a Large Scale Twin Study. J. of Am. Acad. Of Child Adolesc. Psychiatry, 1997, Vol 36: 737-44.

Sherman, D.K., Iacono, W.G., McGue, M.K. Attention-Deficit Hyperactivity Disorder Dimensions: A Twin Study of Inattention and Impulsivity-Hyperactivity. J. of Am. Acad. Of Child Adolesc. Psychiatry, 1997, Vol 36: 737-44.

Scientific American Online: http://www.sciam.com/1998/0998issue/0998barkley.html#link1

Ritalin Action on Hyperactivity Explained By New Theoryhttp://pharmacology.tqn.com/library/99news/bl9n0155d.htm

Approaching a Scientific Understanding of what Happens in the Brain in AD/HDhttp://www.chadd.org/attnv4n1p30.htm

Marx, J. How Stimulant drugs May Clam Hyperactivity. Science, 1999, Vol. 283: 306-08.http://www.sciencemag.org/cgi/content/full/283/5400/306?

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