Attention-Deficit Hyperactivity Disorder

1
Attention-Deficit Hyperactivity Disorder

• By
• Chris Golner
• April 19, 1999
• Biochemistry/Molecular Biology Seminar

2
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.

3
Outline

• History of ADHD
• Symptoms and Diagnosis DSM-IV criteria
• Possible causes
• Treatments
• Stimulants
• Outcome

4
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

5
Diagnosing ADHD DSM-IV

• Lacks attention to detail makes careless
  mistakes
• has difficulty sustaining attention
• doesnt 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

• Inattentiveness
• Has a minimum of 6 symptoms regularly for the
  past six months.
• Symptoms are present at abnormal levels for stage
  of development

6
Diagnosing ADHD DSM-IV

• 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

• Hyperactivity/ Impulsivity

Has a minimum of 6 symptoms regularly for the
past six months. Symptoms are present at
abnormal levels for stage of development
7
Diagnosing ADHD DSM-IV

• 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

• Additional Criteria

8
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

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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.
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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

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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

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Dopamine in the Brain
Scientific American Http//www.sciam.com/1998/0998i
ssue/0998barkely.htmllink1
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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

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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

15
Treatment

• Counseling of individual and family
• Stimulants
• Tricyclic antidepressants
• Bupropion
• Clonidine

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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

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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.

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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

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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 (Tourettes Syndrome)
• overfocussing
• liver problems or rash (Pemoline only)

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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

21
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.

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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.htmllink1
• Ritalin Action on Hyperactivity Explained By New
  Theory
• http//pharmacology.tqn.com/library/99news/bl9n015
  5d.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/283/540
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