Epigenetic mechanisms of depression
Open accessAbstract
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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Alterations of neuronal activity in the mesolimbic system can result in antidepressant-like effects.
“numerous studies have now demonstrated that alterations of neuronal activity in the mesolimbic system can result in antidepressant-like effects (Nestler, 2014; Nestler and Carlezon, 2006; Warner-Schmidt et al., 2012)”
From Mood and anxiety regulation by nicotinic acetylcholine receptors: A potential pathway to modulate aggression and related behavioral states (2015) · cites this paper as Nestler, 2014
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- Authors
- Nestler, E. J.
- Affiliations
- Icahn School of Medicine at Mount Sinai (US)
- Corresponding author
- Nestler, Eric J.
- ORCID
- Nestler, Eric J.
- Venue
- JAMA Psychiatry
- Publisher
- American Medical Association (AMA)
- Published
- 2014-04-01
- Volume
- 71
- Issue
- 4
- Pages
- 454
- ISSN
- 2168-622X (ISSN-L)
- PMC
- PMC4057796
- 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
- green
- www.ncbi.nlm.nih.gov
- 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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