NeurogeneticAdaptiveMechanismsinAlcoholismC.ROBERTCLONINGERClinical,genetic,andneuropsychopharmacologicalstud-iesofdevelopmentalfactorsinalcoholismareprovidingabetterunderstandingoftheneurobiologicalbasesofpersonalityandlearning.Studiesoftheadopted-awaychildrenofalcoholicsshowthatthepredispositiontoinitiatealcohol-seekingbehaviorisgeneticailydifferentfromsusceptibilitytolossofcontrolafterdrinkingbe-gins.Alcohol-seekingbehaviorisaspeialcaseofexplor-atoryappetitivebehaviorandinvolvesdifferentneuroge-neticprocessesthandosuscptibilittobehavioraltoler-anceanddependenceontheantianxietorsedativeeffectsofalcohol.Ihreedimensionsofpesonalityhavebeendescribedthatmayreflectindividualdifferencesinbrainsystemsmodulaltingtheactivation,maintenance,andin-hibitionofbehavioralresponsestotheeffectsofalcoholandotherenvironmentalstimuli.Thesepersonalitytraitsdistinguishalcoholicswithdifferentpaternsofbehavior-al,neurophysiological,andneuropharmacologicalre-sponsestoalcohol.T-sHEINTERACrIONOFGENETICANDENVIRONMENTALFAC-torsinthedevelopmentofvoluntarybehaviors,suchasthedrinkingofalcoholicbeverages,isanimportantandchal-lengingfieldofinvestigationinthebehavioralsciences.ThevastmajorityofpeopleintheUnitedStatesdrinkalcoholicbeverages,buthalfofallthealcoholdrunkisconsumedbyonly10%ofthepopulation(1).Differencesbetweenindividualsinthefrequencyandamountofalcoholthattheyconsume,aswellasdifferencesinresultingcomplications,aredeterminedbymanygeneticandsocio-culturalvariables.Bothconsumptionandcomplicationshavevariedwidelyfromonehistoricaleratoanotherandcurrentlyvaryfromcountrytocountry,amongsocialdasses,amongpersonsofdifferentoccupation,andbetweenmenandwomen(2).Childrenwhoarerearedbyalcoholicadoptiveparentsarenomorelikelytobecomealcoholicthemselvesthanotherchildren;however,childrenofalcoholicbiologicalparentsaremorelikelythanotherchildrentomisusealcohol,evenwhentheyareseparatedfromtheirbiologicalparentsininfancyandplacedinstableadoptivehomes(3).Medicalcomplicationsinvolvingdifferentorgans,suchasliver,heart,brain,andpancreas,havedistinctgeneticinfluences(4).Sincealcoholabuseissofrequentandwidespread,itisnotsurprisingthatitsdevelopmentshouldinvolvetheinteractionofmanydifferentetiologicalfactors(5).Developmentalcomplexityisexpectedforsuchcommondisorders.Nevertheless,investigatorswhoadvocateaparticularetiologicalmodelofalcoholism-psycho-social,psychoanalytic,behaviorallearning,orbiomedical-have410oftenquestionedorignoredthefindingsofinvestigatorsinotherfieldsandhavefailedtorecognizethecompatibilityorcomplemen-taryrelationshipofbothneurobiologicalandpsychosocialfactors(6).Thishasoftenledtosteriledebatesabouttherelativeimpor-tanceofnatureversusnurtureorinstinctversuslearninginthedevelopmentofalcoholism.Nowresearchonalcoholismisatawatershedinwhichwecanbegintodescribethedevelopmentoftheclinicalsignsandsymp-tomsintermsofitsunderlyingpathophysiologicalprocesses.Moreimportantly,themajorneurobiologicalsystemsinvolvedinalcohol-seekingbehaviorandacquisitionoffunmctionaltolerancetoanddependenceonalcoholismappeartocorrespondtobrainsystemsinvolvedinanindividual'sabilitytoadapttonovel,appetitive,andaversivestimuliingeneral,notonlytoalcohol(7).Psychiatricstudiesofalcoholicshaveidentifiedclinicalsubgroupsthatdifferintheirpatternsofabuse,personalitytraits,neurophysiologicalcharac-teristics,andinheritance.Thesesubgroupsarenotdiscretediseaseentities;rather,recentfindingssuggestthattheyresultfromvariouscombinationsofresponsebiasesinbrainsystemsthatmediateanindividual'sadaptationtoexperience,includingtheeffectsofalcoholandotherdrugs.Studiesofpersonalityandlearninginalcoholicsubgroupsandinthegeneralpopulationhaveprovidedinfornationaboutstructureandfunctionoftheseneuroadaptivesystems.Alsoneuropsychopharmacologicalstudiesinhumansandothermammalspermitcharacterizationofthefunctionalorganizationofthebrainsystemsunderlyingpersonalityandlearningingeneralandsuscepti-bilitytoalcoholisminparticular.Inotherwords,theneurogeneticbasisofalcoholismisanimportantspecialcaseintherapidlyadvancingstudyoftheneurobiologyofmotivationandlearning.Manydifferentfieldsofresearchinthebehavioralandneuralsciencescontributeimportantinformationaboutdevelopmentalfactorsinalcoholism,andmanyofthefindingsthatlinktheresultsofonefieldwiththoseoftheothersremaintentative.Ignoranccoftherelevanceofrobustfindingsinonefieldoftenlimitsthedesignandinterpretationofexpernmentsinanotherfield.Forexample,personalityvariationhasahighly
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