Global Brain Gene Expression Analysis Links Glutamatergic and GABAergic Alterations to Suicide and Major Depression 英文参考文献.docVIP

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Global Brain Gene Expression Analysis Links Glutamatergic and GABAergic Alterations to Suicide and Major Depression 英文参考文献.doc

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Global Brain Gene Expression Analysis Links Glutamatergic and GABAergic Alterations to Suicide and Major Depression 英文参考文献

GlobalBrainGeneExpressionAnalysisLinks GlutamatergicandGABAergicAlterationstoSuicideand MajorDepression AdolfoSequeira1¤,FirozaMamdani1,CarlErnst1,MarquisP.Vawter4,WilliamE.Bunney4 ,Veronique Lebel1,SoniaRehal1,TimKlempan1,AlainGratton1,ChawkiBenkelfat2,GuyA.Rouleau3 ,Naguib Mechawar1,GustavoTurecki1* 1McGillGroupforSuicideStudies,DouglasMentalHealthUniversityInstitute,McGillUniversity,Montreal,Quebec,Canada,2RoyalVictoriaHospital,McGillUniversity, Montreal, Quebec, Canada, 3Ste Justine Hospital, Universite′ de Montre′al, Montreal, Quebec, Canada, 4Department of Psychiatry and Human Behavior, School of Medicine,UniversityofCaliforniaIrvine,Irvine,California,UnitedStatesofAmerica Abstract Background: Most studies investigating the neurobiology of depression and suicide have focused on the serotonergic system. While it seems clear that serotonergic alterations play a role in the pathogenesis of these major public health problems, dysfunction in additional neurotransmitter systems and other molecular alterations may also be implicated. Microarrayexpressionstudiesareexcellentscreeningtoolstogeneratehypothesesaboutadditionalmolecularprocesses thatmaybeatplay.Inthisstudyweinvestigatedbrainregionsthatareknowntobeimplicatedintheneurobiologyof suicideandmajordepressionarelikelytorepresentvalidglobalmolecularalterations. Methodology/PrincipalFindings:WeperformedgeneexpressionanalysisusingtheHG-U133ABchipsetin17corticaland subcorticalbrainregionsfromsuicideswithandwithoutmajordepressionandcontrols.TotalmRNAformicroarrayanalysis wasobtainedfrom663brainsamplesisolatedfrom39malesubjects,including26suicidecasesand13controlsdiagnosed bymeansofpsychologicalautopsies.Independentbrainsamplesfrom34subjectsandanimalstudieswereusedtocontrol forthepotentialconfoundingeffectsofcomorbiditywithalcohol.UsingaGeneOntologyanalysisasourstartingpoint,we identifiedmolecularpathwaysthatmaybeinvolvedindepressionandsuicide,andperformedfollow-upanalysesonthese possible targets. Methodology included