Klengel Torsten, Pape Julius, Binder Elisabeth B, Mehta Divya
Department of Translational Research, Max Planck Institute of Psychiatry, Munich 80804, Germany.
Department of Translational Research, Max Planck Institute of Psychiatry, Munich 80804, Germany; Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA 30322, USA.
Neuropharmacology. 2014 May;80:115-32. doi: 10.1016/j.neuropharm.2014.01.013. Epub 2014 Jan 19.
Epigenetic modifications in response to traumatic experience and stress are emerging as important factors in the long-term biological trajectories leading to stress-related psychiatric disorders, reflecting both environmental influences as well as individual genetic predisposition. In particular, recent evidence on DNA methylation changes within distinct genes and pathways but also on a genome-wide level provides new insights into the pathophysiology of stress related psychiatric disorders. This review summarizes current findings and concepts on DNA methylation changes in stress-related disorders with a focus on major depressive disorder and posttraumatic stress disorder (PTSD). We highlight studies of DNA methylation in animals and humans pertinent to these disorders, both focusing on candidate loci as well as genome-wide studies. We describe molecular mechanisms of how exposure to stress can induce long lasting changes in DNA methylation and how these may relate to the pathophysiology of depression and PTSD. We discuss data suggesting that DNA methylation, even in peripheral tissues, appears to be an informative reflection of environmental exposures on the genome and may have potential as a biomarker for the early prevention of stress-related disorders.
对创伤经历和压力产生的表观遗传修饰正逐渐成为导致应激相关精神障碍的长期生物学轨迹中的重要因素，这既反映了环境影响，也反映了个体的遗传易感性。特别是，最近关于不同基因和通路内以及全基因组水平上DNA甲基化变化的证据，为应激相关精神障碍的病理生理学提供了新的见解。本综述总结了应激相关障碍中DNA甲基化变化的当前研究结果和概念，重点关注重度抑郁症和创伤后应激障碍（PTSD）。我们强调了与这些障碍相关的动物和人类DNA甲基化研究，包括对候选基因座的研究以及全基因组研究。我们描述了应激暴露如何诱导DNA甲基化产生持久变化的分子机制，以及这些变化如何与抑郁症和PTSD的病理生理学相关。我们讨论的数据表明，即使在周围组织中，DNA甲基化似乎也是基因组对环境暴露的一种信息性反映，并且可能具有作为应激相关障碍早期预防生物标志物的潜力。
