Attention-Deficit Hyperactivity DisorderADHD StatisticsOutlineHistory of ADHDDiagnosing ADHD: DSM-IVSlide 6Slide 7Problems of DiagnosisADHD and the BrainADHD and the Brain IIWhat causes ADHD?Dopamine in the BrainGenetic Linkages to ADHDDRD4TreatmentStimulantsMethylphenidateEffects of MPHSide EffectsOutcomeReferencesSlide 22Attention-Deficit Hyperactivity DisorderByChris GolnerApril 19, 1999Biochemistry/Molecular Biology SeminarADHD Statistics3-5% of all U.S. school-age children are estimated to have this disorder.5-10% of the entire U.S. populationMales are 3 to 6 times more likely to have ADHD than are females.At least 50% of ADHD sufferers have another diagnosable mental disorder.OutlineHistory of ADHDSymptoms and Diagnosis: DSM-IV criteriaPossible causesTreatmentsStimulants OutcomeHistory of ADHDMid-1800s: Minimal Brain DamageMid 1900s: Minimal Brain Dysfunction1960s: Hyperkinesia1980: Attention-Deficit DisorderWith or Without Hyperactivity1987: Attention Deficit Hyperactivity Disorder1994-present: ADHD Primarily InattentivePrimarily HyperactiveCombined TypeDiagnosing 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 developmentLacks attention to detail; makes careless mistakeshas difficulty sustaining attentiondoesn’t seem to listenfails to follow through/fails to finish projectshas difficulty organizing tasksavoids tasks requiring mental effortoften loses items necessary for completing a taskeasily distracted is forgetful in daily activitiesDiagnosing ADHD: DSM-IVHyperactivity/ Impulsivity:Fidgets or squirms excessivelyleaves seat when inappropriateruns about/climbs extensively when inappropriatehas difficulty playing quietlyoften “on the go” or “driven by a motor”talks excessivelyblurts out answers before question is finishedcannot await turninterrupts or intrudes on othersHas a minimum of 6 symptoms regularly for the past six months.Symptoms are present at abnormal levels for stage of developmentDiagnosing ADHD: DSM-IVAdditional Criteria:Symptoms causing impairment present before age 7Impairment from symptoms occurs in two or more settingsClear evidence of significant impairment (social, academic, etc.)Symptoms not better accounted for by another mental disorderProblems of DiagnosisSubjectivity of CriteriaInconsistent evaluations--presence of symptoms usually given by teacher or parentStudy 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 sourceSymptoms in females more subtle---leads to underdiagnosisADHD and the BrainDiminished arousal of the Nervous SystemDecreased blood flow to prefrontal cortex and pathways connecting to limbic system (caudate nucleus and striatum)PET scan shows decreased glucose metabolism throughout brainComparison of normal brain (left) and brain of ADHD patient.ADHD and the Brain IISimilarities of ADHD symptoms to those from injuries and lesions of frontal lobe and prefrontal cortexMRIs of ADHD patients show:Smaller anterior right frontal lobeabnormal development in the frontal and striatal regionsSignificantly smaller splenium of corpus callosumdecreased communication and processing of information between hemispheresSmaller caudate nucleusWhat causes ADHD?Underlying cause of these differences is still unknown; there is much conflicting data between studiesStrong evidence of genetic componentPredominant theory: Catecholamine neurotransmitter dysfunction or imbalancedecreased dopamine and/or norepinephrine uptake in braintheory supported by positive response to stimulant treatment Recent study indicates possible lack of serotonin as a factor in miceScientific AmericanHttp//www.sciam.com/1998/0998issue/0998barkely.html#link1Dopamine in the BrainGenetic Linkages to ADHDTwin studies by Stevenson, Levy et al, and Sherman et al indicate an average heritability factor of .80Biederman et al reported a 57% risk to offspring if one parent has ADHD. Dopamine genesDA type 2 geneDA transporter gene (DAT1)Dopamine receptor (DRD4, “repeater gene”) is over-represented in ADHD patientsDRD4DRD4 is most likely contributorDRD4 affects the post-synaptic sensitivity in the prefrontal and frontal cortexThis region of cortex affects executive functions and attentionExecutive functions include working memory, internalization of speech, emotions, motivation, and learning of behaviorTreatmentCounseling of individual and familyStimulants Tricyclic antidepressantsBupropion ClonidineStimulantsExact mechanism unknownRaise activity level of the CNS by decreasing fluctuations of activity or lowering threshold needed for arousalSimilar in structure to NE and DA, and may mimic their actionsAt least 75% have positive response with single dose95% respond well to stimulant treatmentInclude methylphenidate, dextroamphetamine and pemolineMethylphenidateIs a piperidine derivative commonly known as Ritalin®Is believed to act as dopamine agonist in synaptic cleftStimulates frontal-striatal regionsDosage (5-20 mg) must be adjusted to each patientTaken orally, 2-3 times a day as neededBehavioral effects start within 1/2 hour to hour after ingestion, peaking at 1 and 3 hoursAlso comes in Sustained-Release form, whose effects last approximately twice as long.Effects of MPHElevates moodRaises arousal of CNS and cerebral blood flowIncreases productivityImproves social interactionsIncreases heart rate and blood pressureHas little or no abuse potentialSide EffectsCommon:decreased appetiteinsomniabehavioral reboundhead and stomach achesAlso thought to cause temporary height and weight suppressionMild:anxiety/ depressionirritabilityRare:tics (Tourette’s Syndrome)overfocussingliver problems or rash (Pemoline only)OutcomeADHD can persist into adulthood, but usually symptoms gradually diminishWhen it persists into adulthood, it usually requires ongoing treatment and counselingmost will develop another disorder (especially learning disability, ODD, depression, and/or conduct disorder)Without treatment:antisocial and
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