Center for Social Epidemiology and Population Health, Department of Epidemiology, University of Michigan School of Public Health, 1415 Washington Heights, Ann Arbor, MI 48109, USA.
Psychol Med. 2011 May;41(5):997-1007. doi: 10.1017/S0033291710001674. Epub 2010 Sep 14.
Recent work suggests that epigenetic differences may be associated with psychiatric disorders. Here we investigate, in a community-based sample, whether methylation profiles distinguish between individuals with and without lifetime depression. We also investigate the physiologic consequences that may be associated with these profiles.
Using whole blood-derived genomic DNA from a subset of participants in the Detroit Neighborhood Health Study (DNHS), we applied methylation microarrays to assess genome-wide methylation profiles for over 14 000 genes in 33 persons who reported a lifetime history of depression and 67 non-depressed adults. Bioinformatic functional analyses were performed on the genes uniquely methylated and unmethylated in each group, and inflammatory biomarkers [interleukin (IL)-6 and C-reactive protein (CRP)] were measured to investigate the possible functional significance of the methylation profiles observed.
Uniquely unmethylated gene sets distinguished between those with versus without lifetime depression. In particular, some processes (e.g. brain development, tryptophan metabolism) showed patterns suggestive of increased methylation among individuals with depression whereas others (e.g. lipoprotein) showed patterns suggestive of decreased methylation among individuals with depression. IL-6 and CRP levels were elevated among those with lifetime depression and, among those with depression only, IL-6 methylation showed an inverse correlation with circulating IL-6 and CRP.
Genome-wide methylation profiles distinguish individuals with versus without lifetime depression in a community-based setting, and show coordinated signals with pathophysiological mechanisms previously implicated in the etiology of this disorder. Examining epigenetic mechanisms in concert with other dynamic markers of physiologic functioning should improve our understanding of the neurobiology of depression.
最近的研究表明，表观遗传差异可能与精神疾病有关。在这里，我们在基于社区的样本中研究了终生抑郁患者与非抑郁患者之间的甲基化谱是否存在差异。我们还研究了可能与这些谱相关的生理后果。
我们从底特律社区健康研究（DNHS）的一部分参与者的全血衍生基因组 DNA 中，使用甲基化微阵列来评估 33 名报告有终生抑郁史的人和 67 名非抑郁成年人的超过 14000 个基因的全基因组甲基化谱。对每个组中唯一甲基化和未甲基化的基因进行了生物信息学功能分析，并测量了炎症生物标志物（白细胞介素 (IL)-6 和 C 反应蛋白 (CRP)），以研究观察到的甲基化谱可能具有的功能意义。
独特的未甲基化基因集区分了有与无终生抑郁的个体。特别是，一些过程（例如大脑发育、色氨酸代谢）在有抑郁的个体中表现出增加甲基化的模式，而其他过程（例如脂蛋白）在有抑郁的个体中表现出减少甲基化的模式。IL-6 和 CRP 水平在有终生抑郁的个体中升高，并且仅在有抑郁的个体中，IL-6 甲基化与循环 IL-6 和 CRP 呈负相关。
在基于社区的环境中，全基因组甲基化谱可区分有与无终生抑郁的个体，并且与以前涉及该疾病病因的生理病理机制表现出协调的信号。与其他生理功能的动态标志物一起检查表观遗传机制应能提高我们对抑郁神经生物学的理解。
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