Stress, epigenetics and depression: A systematic review

Neurosci Biobehav Rev. 2019 Jul;102:139-152. doi: 10.1016/j.neubiorev.2019.04.010. Epub 2019 Apr 18.


Environmental stressors, such as childhood maltreatment, have been recognized to contribute to the development of depression. Growing evidence suggests that epigenetic changes are a key mechanism by which stressors interact with the genome leading to stable changes in DNA structure, gene expression, and behaviour. The current review aimed to evaluate the relationship between stress-associated epigenetic changes and depression. Human studies were identified via systematic searching of PubMed/Medline from inception to February 2018. Seventeen articles were identified. Stress-associated epigenetic changes in the following genes were correlated with depression: NRC31, SLCA4, BDNF, FKBP5, SKA2, OXTR, LINGO3, POU3F1 and ITGB1. Epigenetic changes in glucocorticoid signaling (e.g., NR3C1, FKBP5), serotonergic signaling (e.g. SLC6A4), and neurotrophin (e.g., BDNF) genes appear to be the most promising therapeutic targets for future research. However, continued research is warranted due to inconsistent findings regarding the directionality of epigenetic modification. Future studies should also aim to control for the use of psychotropic agents due to their widespread use in depressed populations and established effects on DNA methylation.

Keywords: BDNF; Childhood maltreatment; Depressive symptoms; Early childhood adversity; Environmental stress; Epigenetics; Major depressive disorder; NRC31; SLCA4.

Publication types

  • Systematic Review

MeSH terms

  • Adult
  • Adverse Childhood Experiences*
  • Child
  • Child Abuse*
  • Depression / etiology
  • Depression / genetics*
  • Depressive Disorder, Major / etiology
  • Depressive Disorder, Major / genetics*
  • Epigenesis, Genetic / genetics*
  • Humans
  • Stress, Psychological / complications
  • Stress, Psychological / genetics*