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Attention-Deficit Hyperactivity Disorder By Chris Golner April 19, 1999 Biochemistry/Molecular Biology Seminar.

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Presentation on theme: "Attention-Deficit Hyperactivity Disorder By Chris Golner April 19, 1999 Biochemistry/Molecular Biology Seminar."— Presentation transcript:

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 Õ Stimulants @Outcome

4 History of ADHD @Mid-1800s: Minimal Brain Damage @Mid 1900s: Minimal Brain Dysfunction @1960s: Hyperkinesia @1980: Attention-Deficit Disorder Õ With or Without Hyperactivity @1987: Attention Deficit Hyperactivity Disorder @1994-present: ADHD Õ Primarily Inattentive Õ Primarily Hyperactive Õ Combined Type

5 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

6 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

7 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

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 ä abnormal development in the frontal and striatal regions ' Significantly smaller splenium of corpus callosum ä 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 ä decreased dopamine and/or norepinephrine uptake in brain ä theory supported by positive response to stimulant treatment @Recent study indicates possible lack of serotonin as a factor in mice

12 Scientific American Http//www.sciam.com/1998/0998issue/0998barkely.html#link1 Dopamine in the Brain

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 ä DA type 2 gene ä DA transporter gene (DAT1) ä 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 (Tourette’s 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: ä antisocial and deviant behavior ä increased rates of divorce, moving violations, incarceration, and institutionalization

21 References Barkley, R. Attention-Deficit Hyperactivity Disorder, 2 nd Ed. New York: Guilford Press. 1998. 628 pp. Shaywitz, B. and Shaywitz, S. Attention Deficit Disorder Comes of Age: Toward the 21 st 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.

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.html#link1http://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&RES ULTFORMAT=&fulltext=Attention+Deficit+Disorder&searchid=QID_NOT_SET&FIRSTIN DEX=


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