Gene expression profiling of depression and suicide in human prefrontal cortex.

Gene expression profiling of depression and suicide in human prefrontal cortex.
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人类前额皮质抑郁和自杀的基因表达谱。

DOI:
10.1038/sj.npp.1300335
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发表时间:
2004
期刊:
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
影响因子:
--
通讯作者:
JohnMann,J
JohnMann,J
中科院分区:
--
文献类型:
--
作者:
Sibille,Etienne;Arango,Victoria;Galfalvy,HangaC;Pavlidis,Paul;Erraji-Benchekroun,Loubna;Ellis,SteveP;JohnMann,J

文献摘要

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情绪障碍是残疾的主要原因。病因包括遗传和环境因素,但负责的基因尚未确定。使用DNA微阵列,我们已经进行了大规模的基因表达分析,在两个区域的人类前额皮质的尸检匹配组的主题与抑郁症谁死于自杀,和控制对象谁死于其他原因,没有精神疾病。生物信息学分析用于研究可能涉及抑郁症和自杀行为的分子和细胞途径。我们测试了疾病病理学及其推定分子影响的几种假设,包括单个基因的变化,患者或疾病亚型亚组的存在,或在疾病过程中共同生物学途径受到影响的可能性。在这项相对较大的基因组研究的分析范围内,我们没有发现与抑郁症和自杀相关的分子差异的证据,这表明病理学低于当前基因组方法的检测水平,或者是定位于其他大脑区域,或者更多地与转录后效应和/或蛋白质水平或功能的变化有关,而不是改变前额叶皮层的转录组。
Mood disorders are a major cause of disability. Etiology includes genetic and environmental factors, but the responsible genes have yet to be identified. Using DNA microarrays, we have conducted a large-scale gene expression analysis, in two regions of the human prefrontal cortex from post-mortem matched groups of subjects with major depression who had died by suicide, and control subjects who died from other causes and were free from psychiatric disorders. Bioinformatic analysis was used to investigate molecular and cellular pathways potentially involved in depression and suicidal behavior. We tested several hypotheses of disease pathology and of their putative molecular impact, including changes in single genes, the existence of subgroups of patients or disease subtypes, or the possibility of common biological pathways being affected in the disease process. Within the analytical limits of this relatively large genomic study, we found no evidence for molecular differences that correlated with depression and suicide, suggesting a pathology that is below the detection level of current genomic approaches, or that is either localized to other brain areas, or more associated with post-transcriptional effects and/or changes in protein levels or functions, rather than altered transcriptome in the prefrontal cortex.