Progress in Epigenetics of Depression

Abstract

Depression is a prevalent and complex psychiatric syndrome. Epigenetic mechanisms bridge the genetic and environmental factors that contribute to the pathophysiology of depression. A surge of research over the last decade has identified changes in DNA methylation, histone modifications, histone organization, and noncoding RNAs associated with depression and stress-induced depression-like behavior in animal models. We focus here on associations of epigenetic factors concurrent with depression and depression-like behavior, although risk for depression and some of the associated epigenetic changes are known to have developmental origins. Finally, emerging technology may enable breakthroughs in the ability to rescue depression-associated epigenetic modifications at specific genes, greatly enhancing specificity of future potential therapeutic treatments.

Keywords: DNA methylation; depression; epigenetic mechanisms; histone modifications; noncoding RNAs.

Fig. 1

(A) Brain regions implicated in major depressive disorder and response to stress, shown on sagittal view of mouse brain. (B) H3K14Ac levels in mouse brain after chronic social defeat stress. Chronic fluoxetine treatment normalizes hippocampal H3K14Ac at 20 days (not shown). Amyg, Amygdala; Hipp, hippocampus; NAc, nucleus accumbens; PFC, prefrontal cortex; VTA, ventral tegmental area. Adapted from Covington HE, Maze I, LaPlant QC, Vialou VF, Ohnishi YN, Berton O, et al. Antidepressant actions of histone deacetylase inhibitors. J Neurosci. 2009;29(37):11451–60. Covington HE, Vialou VF, Laplant Q, Ohnishi YN, Nestler EJ. Hippocampal-dependent antidepressant-like activity of histone deacetylase inhibition. Neurosci Lett. 2011;493(3):122–126. Covington HE III, Maze I, Vialou V, Nestler EJ. Antidepressant action of HDAC inhibition in the prefrontal cortex. Neuroscience. 2015;298:329–335.