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1、DSM-IVNicotineWithdrawalandAlcoholDependence:AssociationFindingswith theNicotinicAcetylcholineAlpha-3, Alpha-5,Beta-4ReceptorGeneCluster inAustralianFamiliesMicheleL.Pergadia1,ArpanaAgrawal1,AndrewC.Heath1,ScottSaccone1,JenC.Wang1,GrantW.Montgomery2,AlexandreA.Todorov1,AlisonGoate1,JohnRice1,Jaakk
2、oKaprio3,RichardD.Todd1,NicholasG.Martin2,andPamelaA.F.Madden11WashingtonUniversitySchoolofMedicine,St.Louis,MO,U.S.A.2QueenslandInstituteofMedicalResearch,Australia3UniversityofHelsinki,FinlandIntroduction:Smoking/ NicotineWithdrawal25%oftheUSadultpopulationcontinuestosmoke(CDC,2002).Over50%ofsmo
3、kersreportsymptomsofnicotinewithdrawalaftertheyquitorcut-down(Breslauetal.,1992;Pergadiaetal.,2006).Upto47%ofthevarianceinnicotinewithdrawalcanbeaccountedforbygeneticfactors(Pergadiaetal.,2006).Introduction:AlcoholUseProblems19%oftheUSadultpopulationhasexperiencedanalcoholusedisorderatsomepointint
4、heirlife(Kessleretal.,2005).Upto47%ofthevarianceinalcoholdependencemaybeaccountedforbygeneticinfluences,evenaftercontrollingfordemographicsandco-morbidpsychopathology(Knopiketal.,2004).Introduction:Nicotineand AlcoholUseProblemsIncreasinglevelsofnicotinewithdrawalseverityareassociatedwithincreased
5、riskofalcoholdependence(Breslauetal.,1992;Maddenetal.,1997;Xianetal.,2004).Thereisevidenceforgeneticoverlapbetweennicotinedependenceandalcoholdependenceinmen(Maddenetal.,Guze2006;Trueetal.,1999),andforgeneticoverlapbetweenhistoryofsmokingandalcoholintoxication,especiallyinwomen(Maddenetal.,1997).E
6、venafteraccountingforregularsmoking,significantphenotypic(r=.15)andgeneticoverlap(rg=.26)isfoundbetweennicotinewithdrawalandalcoholdependence,suggestingthatsomeadditionalgeneticfactorsmightbeaccountingforthecovariationatthislaterstageofsmokingbehavior(nicotinewithdrawal;Pergadiaetal.,Guze2006).Can
7、didateGenesforNicotineWithdrawalPharmacologic(Damajetal.,2003)andgeneticknock-outworkinmice(Salasetal.,2004)implicatetheimportanceofnicotinicacetylcholinealpha-3,alpha-5,beta-4receptorgeneclusterinnicotinewithdra
