Epigenetic mechanisms of depression.

Epigenetic mechanisms of depression.
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DOI:
10.1001/jamapsychiatry.2013.4291
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发表时间:
2014-04
期刊:
影响因子:
25.8
通讯作者:
Nestler, Eric J.
Nestler, Eric J.
中科院分区:
医学1区
文献类型:
--
作者:
Nestler, Eric J.

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越来越多的证据支持这样的假设,即表观遗传学是环境暴露与个体遗传构成相互作用的关键机制,从而决定一生中患抑郁症的风险。从广义上讲,表观遗传学是指在不改变DNA序列的情况下,通过改变染色质结构介导基因表达的稳定变化。根据这一假说,严重的压力会引发——在脆弱的个体中——大脑边缘区域特定基因组位点的染色质结构的变化,这种变化会导致基因表达的持续变化,从而导致抑郁症的发作。这一假设的一个推论是,这种由压力引起的表观遗传修饰也会发生在生命的早期,并有助于决定一个人一生中对随后的压力事件的脆弱性或抵抗力。
Growing evidence supports the hypothesis that epigenetics is a key mechanism through which environmental exposures interact with an individual’s genetic constitution to determine risk for depression throughout life. Epigenetics, in its broadest meaning, refers to stable changes in gene expression that are mediated via altered chromatin structure without modification of DNA sequence. According to this hypothesis, severe stress triggers changes—in vulnerable individuals—in chromatin structure at particular genomic loci in the brain’s limbic regions, which drive sustained changes in gene expression that contribute to episodes of depression. A corollary of this hypothesis is that such stress-induced epigenetic modifications also occur early in life and help determine an individual’s lifetime vulnerability or resistance to subsequent stressful events.
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