Fishberg Department of Neuroscience and Friedman Brain Institute, School of Medicine, New York, NY, USA.
Neuropsychopharmacology. 2013 Jan;38(1):124-37. doi: 10.1038/npp.2012.73. Epub 2012 Jun 13.
Major depressive disorder is a chronic, remitting syndrome involving widely distributed circuits in the brain. Stable alterations in gene expression that contribute to structural and functional changes in multiple brain regions are implicated in the heterogeneity and pathogenesis of the illness. Epigenetic events that alter chromatin structure to regulate programs of gene expression have been associated with depression-related behavior, antidepressant action, and resistance to depression or 'resilience' in animal models, with increasing evidence for similar mechanisms occurring in postmortem brains of depressed humans. In this review, we discuss recent advances in our understanding of epigenetic contributions to depression, in particular the role of histone acetylation and methylation, which are revealing novel mechanistic insight into the syndrome that may aid in the development of novel targets for depression treatment.
重度抑郁症是一种慢性、缓解性综合征，涉及大脑中广泛分布的回路。基因表达的稳定改变，这些改变导致多个脑区的结构和功能变化，与疾病的异质性和发病机制有关。表观遗传事件改变染色质结构以调节基因表达程序，与抑郁相关行为、抗抑郁作用以及动物模型中的抗抑郁或“韧性”有关，越来越多的证据表明，在抑郁人类的死后大脑中也存在类似的机制。在这篇综述中，我们讨论了我们对表观遗传对抑郁症的贡献的最新理解，特别是组蛋白乙酰化和甲基化的作用，这为该综合征提供了新的机制见解，可能有助于开发新的抑郁症治疗靶点。
