Molecular Pathway Reconstruction and Analysis of Disturbed Gene Expression in Depressed Individuals Who Died by Suicide 英文参考文献.docVIP

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Molecular Pathway Reconstruction and Analysis of Disturbed Gene Expression in Depressed Individuals Who Died by Suicide 英文参考文献.doc

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Molecular Pathway Reconstruction and Analysis of Disturbed Gene Expression in Depressed Individuals Who Died by Suicide 英文参考文献

MolecularPathwayReconstructionandAnalysisof DisturbedGeneExpressioninDepressedIndividuals WhoDiedbySuicide VladimirZhurov1,JohnD.H.Stead6,ZulMerali4,5,MiklosPalkovits2,GaborFaludi3,CarolineSchild- Poulter1,HymieAnisman6,MichaelO.Poulter1* 1MolecularBrain ResearchGroup,Robarts ResearchInstitute,UniversityofWesternOntario,London,Ontario,Canada, 2Laboratory for Neuromorphology, Hungarian AcademyofSciencesandSemmelweisUniversity,Budapest,Hungary,3SemmelweisUniversityHospital,Budapest,Hungary,4UniversityofOttawaInstituteofMental HealthResearch,Ottawa,Ontario,Canada,5DepartmentsofPsychology,PsychiatryandCellularandMolecularMedicine,UniversityofOttawa,Ottawa,Ontario,Canada, 6DepartmentofNeuroscience,CarletonUniversity,Ottawa,Ontario,Canada Abstract Molecularmechanismsbehindtheetiologyandpathophysiologyofmajordepressivedisorderandsuicideremainlargely unknown. Recent molecular studies of expression of serotonin, GABA and CRH receptors in various brain regions have demonstrated that molecular factors may contribute to the development of depressive disorder and suicide behaviour. Here,weusedmicroarrayanalysistoexaminetheexpressionofgenesinbraintissue(frontopolarcortex)ofindividualswho had been diagnosed with major depressive disorder and died by suicide, and those who had died suddenly without a historyofdepression.Weanalyzedthelistofdifferentiallyexpressedgenesusingpathwayanalysis,whichisanassumption- freeapproachtoanalyzemicroarraydata.Ouranalysisrevealedthatthedifferentiallyexpressedgenesformedfunctional networks that were implicated in cell to cell signaling related to synapse maturation, neuronal growth and neuronal complexity.Wefurthervalidatedthesedatabyrandomlychoosing(100times)similarlysizedgenelistsandsubjectingthese liststothesameanalyses.Randomgenelistsdidnotprovidehighlyconnectedgenenetworkslikethosegeneratedbythe differentiallyexpressedlistderivedfromoursamples.Wealsofoundthroughcorrelationalanalysisthatthegeneexpression of control participants was more h