Patterns of gene expression in the limbic system of suicides with and without major depression

被引:0
作者
A Sequeira
T Klempan
L Canetti
J ffrench-Mullen
C Benkelfat
G A Rouleau
G Turecki
机构
[1] McGill Group for Suicide Studies,
[2] Douglas Hospital,undefined
[3] McGill University,undefined
[4] Gene Logic Inc.,undefined
[5] 3Current address: Department of Psychiatry and Human Behavior,undefined
[6] College of Medicine,undefined
[7] University of California,undefined
[8] Irvine,undefined
[9] CA,undefined
[10] USA,undefined
来源
Molecular Psychiatry | 2007年 / 12卷
关键词
microarray; gene expression; depression; suicide; limbic system; RT-PCR;
D O I
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摘要
The limbic system has consistently been associated with the control of emotions and with mood disorders. The goal of this study was to identify new molecular targets associated with suicide and with major depression using oligonucleotide microarrays in the limbic system (amygdala, hippocampus, anterior cingulate gryus (BA24) and posterior cingulate gyrus (BA29)). A total of 39 subjects were included in this study. They were all male subjects and comprised 26 suicides (depressed suicides=18, non depressed suicides=8) and 13 matched controls. Brain gene expression analysis was carried out on human brain samples using the Affymetrix HG U133 chip set. Differential expression in each of the limbic regions showed group-specific patterns of expression, supporting particular neurobiological mechanisms implicated in suicide and depression. Confirmation of genes selected based on their significance and the interest of their function with reverse transcriptase-polymerase chain reaction showed consistently correlated signals with the results obtained in the microarray analysis. Gene ontology analysis with differentially expressed genes revealed an overrepresentation of transcription and metabolism-related genes in the hippocampus and amygdala, whereas differentially expressed genes in BA24 and BA29 were more generally related to RNA-binding, regulation of enzymatic activity and protein metabolism. Limbic expression patterns were most extensively altered in the hippocampus, where processes related to major depression were associated with altered expression of factors involved with transcription and cellular metabolism. Additionally, our results confirm previous evidence pointing to global alteration of gabaergic neurotransmission in suicide and major depression, offering new avenues in the study and possibly treatment of such complex disorders. Overall, these data suggest that specific patterns of expression in the limbic system contribute to the etiology of depression and suicidal behaviors and highlight the role of the hippocampus in major depression.
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页码:640 / 655
页数:15
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共 457 条
  • [31] Steingard RJ(2004)Modulation of cortical-limbic pathways in major depression: treatment-specific effects of cognitive behavior therapy Arch Gen Psychiatry 61 34-41
  • [32] Renshaw PF(2005)The stress system in the human brain in depression and neurodegeneration Ageing Res Rev 4 141-194
  • [33] Young AD(2002)Higher expression of serotonin 5-HT(2A) receptors in the postmortem brains of teenage suicide victims Am J Psychiat 159 419-429
  • [34] Yurgelun-Todd DA(2003)Abnormal expression and functional characteristics of cyclic adenosine monophosphate response element binding protein in postmortem brain of suicide subjects Arch Gen Psychiatry 60 273-282
  • [35] Bremner JD(2001)Reduced activation and expression of ERK1/2 MAP kinase in the post-mortem brain of depressed suicide subjects J Neurochem 77 916-928
  • [36] Narayan M(2004)Decreased catalytic activity and expression of protein kinase C isozymes in teenage suicide victims: a postmortem brain study Arch Gen Psychiatry 61 685-693
  • [37] Anderson ER(2004)Altered 5-HT2A and 5-HT4 postsynaptic receptors and their intracellular signalling systems IP3 and cAMP in brains from depressed violent suicide victims Neuropsychobiology 49 189-195
  • [38] Staib LH(2001)The neurobiology and genetics of suicide and attempted suicide: a focus on the serotonergic system Neuropsychopharmacology 24 467-477
  • [39] Miller HL(2004)Genetics of suicide: an overview Harv Rev Psychiatry 12 1-13
  • [40] Charney DS(1990)Psychiatric findings in Wolfram syndrome homozygotes The Lancet 336 667-669