attention-deficit hyperactivity disorder by chris golner april 19, 1999 biochemistry/molecular...
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Attention-Deficit Hyperactivity Disorder
By
Chris Golner
April 19, 1999
Biochemistry/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. population
Males are 3 to 6 times more likely to have ADHD than are females.
At least 50% of ADHD sufferers have another diagnosable mental disorder.
Outline
History of ADHD
Symptoms and Diagnosis: DSM-IV criteria
Possible causes
Treatments Stimulants
Outcome
History of ADHDMid-1800s: Minimal Brain Damage
Mid 1900s: Minimal Brain Dysfunction
1960s: Hyperkinesia
1980: 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 Criteria
Inconsistent evaluations--presence of symptoms usually given by teacher or parent
Study 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 II
Similarities 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 regions
Significantly smaller splenium of corpus callosumdecreased 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 ADHD
Twin 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 genes DA type 2 gene DA transporter gene (DAT1) Dopamine receptor (DRD4, “repeater gene”) is
over-represented in ADHD patients
DRD4
DRD4 is most likely contributor
DRD4 affects the post-synaptic sensitivity in the prefrontal and frontal cortex
This region of cortex affects executive functions and attention
Executive functions include working memory, internalization of speech, emotions, motivation, and learning of behavior
Treatment
Counseling of individual and family
Stimulants
Tricyclic antidepressants
Bupropion
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 mood
Raises arousal of CNS and cerebral blood flow
Increases productivity
Improves social interactions
Increases heart rate and blood pressure
Has 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 Theory
http://pharmacology.tqn.com/library/99news/bl9n0155d.htm
Approaching a Scientific Understanding of what Happens in the Brain in AD/HD
http://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?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=&fulltext=Attention+Deficit+Disorder&searchid=QID_NOT_SET&FIRSTINDEX=