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 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.OutlineHistory of ADHDSymptoms and Diagnosis: DSM-IV criteriaPossible causesTreatmentsStimulants OutcomeHistory 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 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 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 activitiesDiagnosing 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 othersHas a minimum of 6 symptoms regularly for the past six months.Symptoms are present at abnormal levels for stage of developmentDiagnosing 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 disorderProblems 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 underdiagnosisADHD 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 brainComparison of normal brain (left) and brain of ADHD patient.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 nucleusWhat 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 miceScientific AmericanHttp//www.sciam.com/1998/0998issue/0998barkely.html#link1Dopamine in the BrainGenetic 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 patientsDRD4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 behaviorTreatmentCounseling of individual and familyStimulants Tricyclic antidepressantsBupropion ClonidineStimulants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 pemolineMethylphenidate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.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 potentialSide 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)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