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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

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attention deficit hyperactivity disorder
Attention-Deficit Hyperactivity Disorder

By

Chris Golner

April 19, 1999

Biochemistry/Molecular Biology Seminar

adhd statistics
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
Outline
  • History of ADHD
  • Symptoms and Diagnosis: DSM-IV criteria
  • Possible causes
  • Treatments
    • Stimulants
  • Outcome
history of adhd
History of ADHD
  • Mid-1800s: Minimal Brain Damage
  • Mid 1900s: Minimal Brain Dysfunction
  • 1960s: Hyperkinesia
  • 1980: Attention-Deficit Disorder
    • With or Without Hyperactivity
  • 1987: Attention Deficit Hyperactivity Disorder
  • 1994-present: ADHD
    • Primarily Inattentive
    • Primarily Hyperactive
    • Combined Type
diagnosing adhd dsm iv
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 iv1
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 iv2
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
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 brain
ADHD and the Brain
  • Diminished arousal of the Nervous System
  • Decreased 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
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 callosum
      • decreased communication and processing of information between hemispheres
    • Smaller caudate nucleus
what causes adhd
What causes ADHD?
  • Underlying cause of these differences is still unknown; there is much conflicting data between studies
  • Strong evidence of genetic component
  • Predominant 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
dopamine in the brain
Dopamine in the Brain

Scientific American

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

genetic linkages to adhd
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
slide14
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
Treatment
  • Counseling of individual and family
  • Stimulants
  • Tricyclic antidepressants
  • Bupropion
  • Clonidine
stimulants
Stimulants
  • Exact mechanism unknown
  • Raise 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 treatment
  • Include methylphenidate, dextroamphetamine and pemoline
methylphenidate
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
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
Side Effects
  • Common:
      • decreased appetite
      • insomnia
      • behavioral rebound
      • head and stomach aches
  • Also thought to cause temporary height and weight suppression
  • Mild:
      • anxiety/ depression
      • irritability
  • Rare:
      • tics (Tourette’s Syndrome)
      • overfocussing
      • liver problems or rash (Pemoline only)
outcome
Outcome
  • ADHD can persist into adulthood, but usually symptoms gradually diminish
  • When it persists into adulthood, it usually requires ongoing treatment and counseling
  • most will develop another disorder (especially learning disability, ODD, depression, and/or conduct disorder)
  • Without treatment:
    • antisocial and deviant behavior
    • increased rates of divorce, moving violations, incarceration, and institutionalization
references
References

Barkley, 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.

references1
References

Levy, 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=