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Epigenetic Mechanisms of Depression

By Eric J. Nestler MD, PhD

JAMA Psychiatry.
Published online February 05, 2014. doi:10.1001/jamapsychiatry.2013.4291

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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