Attention deficit Hyperactivity disorder
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Attention-Deficit Hyperactivity Disorder By Chris Golner April 19, 1999 Biochemistry/Molecular Biology Seminar
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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.
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Outline History of ADHD Symptoms and Diagnosis: DSM-IV criteria Possible causes Treatments Stimulants Outcome
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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
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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
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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
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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
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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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Scientific American Http//www.sciam.com/1998/0998issue/0998barkely.html#link1 Dopamine in the Brain
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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
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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 (Tourette’s 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
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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.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=
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