ATTENTION DEFICIT/HYPERACTIVITY DISORDER (ADHD) SYMPTOMS AND DIAGNOSIS: A CLUSTER OF THREE SYMPTOMS: Motor hyperactivity Impulsivity: often involving low tolerance for frustration or attempts at control, sometimes tantrums and aggression Attentional deficits DSM-IV combines the above into 3 sub-types: Primarily attentional deficits Motor hyperactivity + impulsivity Combined - all of the above AGE AT ONSET: Usually by 8 yrs THE PROBLEM OF DIAGNOSIS: One of the most over-diagnosed disorders in the US! Such over-diagnosis typically occurs in the school - Any disruptive or non-compliant child is at risk of such diagnosis True US incidence is not above 4% In some school systems, 12% of children are being treated for ADHD EPIDEMIOLOGY: FOUR TO SIX TIMES AS LIKELY IN BOYS WHEN PROPERLY DIAGNOSED, NO GEOGRAPHIC, ETHNIC OR RESIDENTIAL TRENDS GENETICS: As usual there seems to be a substantial genetic component, in that parents and siblings often have psychiatric disorders, but NOT always ADHD! PROGNOSIS: DURATION: A subject of considerable confusion! Once thought to resolve by early adulthood Now know that many of the symptoms persist well into adulthood in at least 1/3rd of ADHD kids HOWEVER, unlike many another psychiatric disorder, this one does NOT worsen, almost certainly improves over the course of the entire life span ACADEMIC PROBLEMS: ADHD kids almost invariably have severe academic problems Often resulting in poor earning potential, early school leaving, etc SOCIAL PROBLEMS: When either motor hyperactivity or impulsivity dominate the clinical picture, the patient also commonly has great problems with the peer group COMORBIDITY: In about 1/3rd of cases, ADHD is accompanied by or becomes: Conduct disorder/antisocial personality And/or substance abuse TREATMENT: Responds well to stimulants in 75% of cases COMMON STIMULANTS INCLUDE: Methylphenidate (Ritalin) - not chemically related to amphetamine, apparently releases dopamine from vesicular stores - relatively rapidly metabolized, requires 3-4 doses/day + Has fewer autonomic effects than the amphetamines Amphetamines Pemoline: not related to the amphetamines, releases dopamine somehow in animals + Also has few autonomic effects + has longer-lasting effect than Ritalin REBOUND PROBLEMS: As the drugs wear off, serious rebound of ADHD symptoms occurs SIDE EFFECTS: Tachycardia, elevated blood pressure Insomnia Anorexia, weight loss Very moderate growth stunting Dysphoria Side effects of Pemoline: + Movement disorders + jaundice - requires regular monitoring of liver function OTHER DRUGS USED TO TREAT ADHD: Usually given only if the child does not respond to stimulants Bupropion: Efficacious, relatively low side-effects TCAs: Rarely, due to major side-effects Clonidine, other à-adrenergic agonists + again side effects, including cardiovascular problems and sedation, are a problem CAUSES: NOT CAUSED BY: Food Additives Sugar DOES RESPONSE TO AMPHETAMINE SUGGEST MONOAMINE ABNORMALITIES? MOST people respond positively to low doses of stimulants! + One explanation for the heavy use of Ritalin in the educational system: it works on every one! Genetic considerations do suggest a possible abnormality in the dopamine system BRAIN SCANS SUGGEST A PARADOXICAL LOWERING OF CEREBRAL ACTIVATION NARCOLEPSY STIMULANTS ARE GIVEN TO TREAT THIS RARE DISEASE PARKINSON'S DISEASE CAUSE: DEATH OF OVER 80% OF NIGRAL DOPAMINE NEURONS ACCOMPANIED BY MASSIVE CELL DEATH IN THE LOCUS CERULEUS ALSO LESS DEVASTATING LOSS IN VTA PROBABLY RELATED NEUROPEPTIDES ALSO LOST WHY? NO ONE KNOWS No known genetic predisposition Search for all sorts of environmental toxins has so far failed Known toxins: + Manganese + MPTP + Influenza epidemic of 1918 SYMPTOMS: BRADYKINESIA: slow, infrequent movement MUSCULAR RIGIDITY: Resistance to involuntary limb movements, "cogwheel" movements of joints RESTING TREMOR: Disappears when asleep ABNORMALITIES IN POSTURE AND GAIT: Stooped, shuffling movement MENTAL ABNORMALITIES: Depression Perseveration Slowing PROGNOSIS: Bleak, progresses to being bed-ridden, pneumonia INCIDENCE: Over 1% of those over 65; no sex differences TREATMENT: REPLACE THE DOPAMINE! Give L-DOPA, a form which gets across the blood- brain barrier Plus a dopa decarboxylase inhibitor which can't cross the blood-brain barrier, prevents L-DOPA from being metabolized before reaching the brain + These are compounds such as carbidopa or benserazide SIDE EFFECTS OF L-DOPA TREATMENT: Orthostatic hypotension: Dopamine is the neuro- transmitter in inhibitory interneurons in the sympathetic nervous system Nausea: overstimulation of the emesis center: occurs in over 70% of patients, can be treated with neuroleptics like domperidone, which don't cross the blood-brain barrier Extrapyramidal side effects - involuntary movements occur in 80% by end of first year Sexual arousal in males Insomnia, arousal Less common, long-term effects include psychotic episodes The "on-off" phenomenon: Drug-related dyskinesias begin to fluctuate with returning symptoms + By the end of 5 years half of all patients experience this therapeutic failure, by 10 years virtually all do Consequently L-DOPA is not a cure, but does prolong relatively normal functioning by as much as 5 to ten years OTHER TREATMENTS: ANTICHOLINERGICS: Amantadine, benztropine can help relieve rigidity and tremor, but at the cost of often- severe cognitive side-effects in the elderly DEPRENYL: A MAO-B inhibitor, sometimes slows progress of the disease while increasing dopaminergic activity BRAIN TRANSPLANTS: Still highly experimental, done in Sweden in a small number of cases Tissue is from own adrenals, or from fetal substantia nigra PACEMAKERS IMPLANTED IN MOTOR NUCLEI OF THE THALAMUS Major target of the striatal system Glowing early reports, as always