Fishberg Department of Neuroscience and Friedman Brain Institute, Mount Sinai School of Medicine, New York, New York 10029, USA.
Annu Rev Pharmacol Toxicol. 2013;53:59-87. doi: 10.1146/annurev-pharmtox-010611-134540. Epub 2012 Sep 27.
Epigenetic mechanisms, which control chromatin structure and function, mediate changes in gene expression that occur in response to diverse stimuli. Recent research has established that environmental events and behavioral experience induce epigenetic changes at particular gene loci and that these changes help shape neuronal plasticity and function and hence behavior. Some of these changes can be stable and can even persist for a lifetime. Increasing evidence supports the hypothesis that aberrations in chromatin remodeling and subsequent effects on gene expression within limbic brain regions contribute to the pathogenesis of depression and other stress-related disorders such as post-traumatic stress disorder and other anxiety syndromes. Likewise, the gradually developing but persistent therapeutic effects of antidepressant medications may be achieved in part via epigenetic mechanisms. This review discusses recent advances in our understanding of the epigenetic regulation of stress-related disorders and focuses on three distinct aspects of stress-induced epigenetic pathology: the effects of stress and antidepressant treatment during adulthood, the lifelong effects of early-life stress on subsequent stress vulnerability, and the possible transgenerational transmission of stress-induced abnormalities.
表观遗传机制控制着染色质的结构和功能，介导了基因表达的变化，这些变化是对各种刺激的反应。最近的研究已经确定，环境事件和行为经验会在特定的基因座诱导表观遗传变化，这些变化有助于塑造神经元的可塑性和功能，从而影响行为。其中一些变化是稳定的，甚至可以持续一生。越来越多的证据支持这样一种假设，即染色质重塑的异常以及随后对边缘脑区基因表达的影响，导致了抑郁症和其他与应激相关的障碍（如创伤后应激障碍和其他焦虑综合征）的发病机制。同样，抗抑郁药物逐渐发展但持久的治疗效果可能部分是通过表观遗传机制实现的。本文综述了我们对与应激相关障碍的表观遗传调控的理解的最新进展，并重点讨论了应激诱导的表观病理的三个不同方面：成年期应激和抗抑郁治疗的影响、生命早期应激对随后应激易感性的终身影响，以及应激诱导异常的可能跨代传递。
