Preclinical and Clinical Evidence of DNA Methylation Changes in Response to Trauma and Chronic Stress.
Preclinical and Clinical Evidence of DNA Methylation Changes in Response to Trauma and Chronic Stress.
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DOI：
10.1177/2470547017710764
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发表时间：
2017-02-01
期刊：
影响因子：
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通讯作者：
Binder EB
中科院分区：
文献类型：
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作者：
Matosin N;Cruceanu C;Binder EB
暴露于慢性压力，无论是反复的严重急性压力还是中度持续压力，都是造成创伤后应激障碍和抑郁症等精神病理学的最大风险因素之一。慢性压力与几种持久的生物学后果有关，特别是与压力内分泌系统有关，但也影响中间表型，例如大脑结构和功能、免疫功能和行为。虽然遗传易感性赋予一定比例的风险，最相关的分子机制决定那些易受压力和创伤的影响和弹性可能是表观遗传。表观遗传学是指通过动态改变基因转录和翻译模式来调控基因组信息的机制。来自临床前啮齿动物和临床人群研究的越来越多的证据强烈支持表观遗传修饰可以在创伤和慢性应激反应中发生。在这里，我们讨论这一文献检查压力引起的表观遗传变化的临床前模型和临床队列的压力和创伤发生在生命早期或成年。我们强调，随着时间的推移，环境压力源和遗传易感性的时间之间的复杂关系可能介导对慢性压力的反应，并且需要通过纵向和死后脑临床队列的进一步调查更好地了解表观遗传变化。
Exposure to chronic stress, either repeated severe acute or moderate sustained stress, is one of the strongest risk factors for the development of psychopathologies such as post-traumatic stress disorder and depression. Chronic stress is linked with several lasting biological consequences, particularly to the stress endocrine system but also affecting intermediate phenotypes such as brain structure and function, immune function, and behavior. Although genetic predisposition confers a proportion of the risk, the most relevant molecular mechanisms determining those susceptible and resilient to the effects of stress and trauma may be epigenetic. Epigenetics refers to the mechanisms that regulate genomic information by dynamically changing the patterns of transcription and translation of genes. Mounting evidence from preclinical rodent and clinical population studies strongly support that epigenetic modifications can occur in response to traumatic and chronic stress. Here, we discuss this literature examining stress-induced epigenetic changes in preclinical models and clinical cohorts of stress and trauma occurring early in life or in adulthood. We highlight that a complex relationship between the timing of environmental stressors and genetic predispositions likely mediate the response to chronic stress over time, and that a better understanding of epigenetic changes is needed by further investigations in longitudinal and postmortem brain clinical cohorts.