Stress, epigenetics and depression: A systematic review

Caroline Park; Joshua D Rosenblat; Elisa Brietzke; Zihang Pan; Yena Lee; Bing Cao; Hannah Zuckerman; Anastasia Kalantarova; Roger S McIntyre

doi:10.1016/j.neubiorev.2019.04.010

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.

Authors

Caroline Park¹, Joshua D Rosenblat², Elisa Brietzke³, Zihang Pan⁴, Yena Lee⁴, Bing Cao⁵, Hannah Zuckerman⁶, Anastasia Kalantarova⁶, Roger S McIntyre⁷

Affiliations

¹ Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, ON, Canada; Institute of Medical Science, University of Toronto, Toronto, ON, Canada. Electronic address: caroline.park@mail.utoronto.ca.
² Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, ON, Canada; Department of Pharmacology, University of Toronto, Toronto, ON, Canada; Department of Psychiatry, University of Toronto, Toronto, ON, Canada.
³ Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, ON, Canada; Department of Psychiatry, Federal University of São Paulo, São Paulo, SP, Brazil.
⁴ Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, ON, Canada; Institute of Medical Science, University of Toronto, Toronto, ON, Canada.
⁵ Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, ON, Canada; School of Public Health, Peking University, Beijing, 100191, PR China.
⁶ Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, ON, Canada.
⁷ Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, ON, Canada; Institute of Medical Science, University of Toronto, Toronto, ON, Canada; Department of Pharmacology, University of Toronto, Toronto, ON, Canada; Department of Psychiatry, University of Toronto, Toronto, ON, Canada; Brain and Cognition Discovery Foundation, Toronto, ON, Canada.

PMID: 31005627
DOI: 10.1016/j.neubiorev.2019.04.010

Abstract

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*