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Attention-Deficit Hyperactivity Disorder

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Title: 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

9
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.
10
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

11
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

12
Dopamine in the Brain
Scientific American Http//www.sciam.com/1998/0998i
ssue/0998barkely.htmllink1
13
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

14
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

16
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

17
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.

18
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

19
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)

20
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.

22
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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