Major depression inParkinson's disease andthemood responsetointravenous methylphenidate: possible role ofthe"hedonic" dopamine synapse

SUMMARY Theeuphoric responsetoequivalent doses ofintravenous methylphenidate (MTP)was assessed ina groupof13Parkinsonian patients affected bymajordepression, ina groupof11 nondepressed Parkinsonians, ina groupof14nonparkinsonian subjects suffering frommajor depression, andfinally ina groupof12controls with noCNSorpsychiatric disease. Subjects ofall four groupswerematched forage,sexandother maincharacteristics. Depressed andnondepressed Parkinsonians were alsomatched forduration andseverity ofillness, andforthetypeof antiparkinsonian treatment. TheresponsetoMTP wasevaluated inthecontext ofadouble-blind, placebo-controlled study. Parkinsonian patients withmajor depression exhibited asignificant lack of sensitivity totheeuphoriant effects ofMTP,incomparison withtheother three groups.Euphoria produced bycentral stimulants hasbeenshowntodepend on theactivity ofadopamine synapsein humans, which isthought tobesituated atthelimbic terminals ofdopamine neuronslocated inthe ventral tegmental area.Degeneration ofthis system may havepredisposed ourParkinsonian patients tomajor depression. Manyinvestigators havebeenintrigued bythepossibility that there arespecific aetiological mechanisms ofdepression inParkinson's disease. Gothametal' havediscussed theinconsistencies ofmostoftheir results. Since Parkinsonians suffer fromachronic disability, they areunquestionably prone to"reactive" depression. However, mostauthors,2-5 though not Horn6 andGothametal' reached theconclusion that adverse moodchanges aremorefrequent among Parkinsonians thanamongother, equally disabled, patients. This, andthefact thatdepression often antedates thecardinal features ofParkinson's disease7'°cannotbeimmediately reconciled withamerely reactive aetiology. Ifthedepression werepurely reactive, adirect correlation between disease duration orseverity anddegree ofdepression should befound. Warburton,2 Celesia andWanamaker,7 Marshand Markham3 andMayeuxetal9foundnoneand Mayeuxetal,' aswell asGothametal,' foundonly a