title: Molecular pathway reconstruction and analysis of disturbed gene expression in depressed individuals who died by suicide.
abstract: Molecular mechanisms behind the etiology and pathophysiology of major depressive disorder and suicide remain largely 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, we used microarray analysis to examine the expression of genes in brain tissue (frontopolar cortex) of individuals who had been diagnosed with major depressive disorder and died by suicide, and those who had died suddenly without a history of depression. We analyzed the list of differentially expressed genes using pathway analysis, which is an assumption-free approach to analyze microarray data. Our analysis revealed that the differentially expressed genes formed functional networks that were implicated in cell to cell signaling related to synapse maturation, neuronal growth and neuronal complexity. We further validated these data by randomly choosing (100 times) similarly sized gene lists and subjecting these lists to the same analyses. Random gene lists did not provide highly connected gene networks like those generated by the differentially expressed list derived from our samples. We also found through correlational analysis that the gene expression of control participants was more highly coordinated than in the MDD/suicide group. These data suggest that among depressed individuals who died by suicide, wide ranging perturbations of gene expression exist that are critical for normal synaptic connectively, morphology and cell to cell communication.
authors.affiliation: Molecular Brain Research Group, Robarts Research Institute, University of Western Ontario, London, Ontario, Canada.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Zhurov
authors.forename: John D H
authors.initials: JD
authors.lastname: Stead
authors.forename: Zul
authors.initials: Z
authors.lastname: Merali
authors.forename: Miklos
authors.initials: M
authors.lastname: Palkovits
authors.forename: Gabor
authors.initials: G
authors.lastname: Faludi
authors.forename: Caroline
authors.initials: C
authors.lastname: Schild-Poulter
authors.forename: Hymie
authors.initials: H
authors.lastname: Anisman
authors.forename: Michael O
authors.initials: MO
authors.lastname: Poulter
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003863:Depression / Q000235:genetics*; D003865:Major Depressive Disorder / Q000235:genetics; D005260:Female; D015870:Gene Expression / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D013405:Suicide