The role of DNA methylation in stress-related psychiatric disorders

Neuropharmacology. 2014 May:80:115-32. doi: 10.1016/j.neuropharm.2014.01.013. Epub 2014 Jan 19.


Epigenetic modifications in response to traumatic experience and stress are emerging as important factors in the long-term biological trajectories leading to stress-related psychiatric disorders, reflecting both environmental influences as well as individual genetic predisposition. In particular, recent evidence on DNA methylation changes within distinct genes and pathways but also on a genome-wide level provides new insights into the pathophysiology of stress related psychiatric disorders. This review summarizes current findings and concepts on DNA methylation changes in stress-related disorders with a focus on major depressive disorder and posttraumatic stress disorder (PTSD). We highlight studies of DNA methylation in animals and humans pertinent to these disorders, both focusing on candidate loci as well as genome-wide studies. We describe molecular mechanisms of how exposure to stress can induce long lasting changes in DNA methylation and how these may relate to the pathophysiology of depression and PTSD. We discuss data suggesting that DNA methylation, even in peripheral tissues, appears to be an informative reflection of environmental exposures on the genome and may have potential as a biomarker for the early prevention of stress-related disorders.

Keywords: DNA methylation; Epigenetics; Gene by environment interaction; PTSD; Stress-related disorders; Trauma.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Brain / enzymology
  • Brain / metabolism*
  • DNA Methylation*
  • Depressive Disorder, Major / etiology
  • Depressive Disorder, Major / metabolism*
  • Epigenesis, Genetic*
  • Gene Expression Regulation
  • Gene-Environment Interaction*
  • Humans
  • Hypothalamo-Hypophyseal System / enzymology
  • Hypothalamo-Hypophyseal System / metabolism
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • Neurons / enzymology
  • Neurons / metabolism*
  • Peripheral Nerves / enzymology
  • Peripheral Nerves / metabolism
  • Pituitary-Adrenal System / enzymology
  • Pituitary-Adrenal System / innervation
  • Pituitary-Adrenal System / metabolism
  • Stress Disorders, Post-Traumatic / enzymology
  • Stress Disorders, Post-Traumatic / metabolism*
  • Stress, Physiological
  • Stress, Psychological / psychology


  • Nerve Tissue Proteins