Chapter 4 - Stress-Mediated Regulation of the DNA Methylome

Abstract

Exposure to stressful life events is considered a major risk factor predisposing individuals to stress-related psychiatric disorders such as major depressive disorder and posttraumatic stress disorder. Mounting evidence indicates that epigenetic mechanisms, such as DNA methylation, mediate basal and pathological changes in gene expression within critical neural circuits in response to stress exposure, which may perpetuate altered neuroendocrine and brain function throughout the lifespan. In this chapter, we review recent clinical and preclinical literature supporting the notion that the DNA methylome (i.e., covalent DNA modifications) is dynamically regulated within the brain in response to stress throughout both pre- and postnatal periods. We highlight the challenges to this field and emphasize the need for cutting-edge research strategies to further our understanding of the establishment, maintenance, and potential reversibility of stress-induced DNA methylation and its consequences of relevance to novel therapeutic strategies for stress-related psychiatric disorders.