Cited by 217Epigenetics and DNA MethylationStress Responses and CortisolGenomics and Chromatin Dynamics

Epigenetic mechanisms of depression

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Nestler, Eric J.·2014·JAMA Psychiatry

Abstract

Growing evidence supports the hypothesis that epigenetics is a key mechanism through which environmental exposures interact with an individual’s genetic constitution to determine risk for depression throughout life.(1) Epigenetics, in its broadest meaning, refers to stable changes in gene expression that are mediated via altered chromatin structure without modification of DNA sequence. According to this hypothesis, severe stress triggers changes—in vulnerable individuals—in chromatin structure at particular genomic loci in the brain’s limbic regions, which drive sustained changes in gene expression that contribute to episodes of depression. A corollary of this hypothesis is that such stress-induced epigenetic modifications also occur early in life and help determine an individual’s lifetime vulnerability or resistance to subsequent stressful events.

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Authors
Nestler, E. J.
Affiliations
Icahn School of Medicine at Mount Sinai (US)
Corresponding author
Nestler, Eric J.
Venue
JAMA Psychiatry
Published
2014-04-01
Volume
71
Issue
4
Pages
454
ISSN
2168-622X (ISSN-L)
OpenAlex
W2042787057
Cited by
217
References
10
Citations by year
2026: 9 · 2025: 17 · 2024: 16 · 2023: 12 · 2022: 21 · 2021: 11 · 2020: 14 · 2019: 19 · 2018: 32 · 2017: 11 · 2016: 22 · 2015: 23 · 2014: 10
FWCI
9.03
Type
journal article
Language
en
Open access
Locations
  • JAMA Psychiatry (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institute of Mental Health (P50MH096890, R01MH051399)
  • National Institute on Drug Abuse (P01DA008227, R01DA007359)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
  • Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
Keywords
depression, epigenetics, gene-environment interaction, chromatin structure, gene expression, stress, limbic system, early life stress, depression vulnerability, DNA methylation
MeSH terms
Animals, Arousal, Brain, Depressive Disorder, Humans, Risk Factors, Stress, Psychological, Genetic Predisposition to Disease, Epigenesis, Genetic, Mice, Resilience, Psychological, Gene-Environment Interaction

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