Epigenetic basis of mental illness
Open accessAbstract
Psychiatric disorders are complex multifactorial illnesses involving chronic alterations in neural circuit structure and function as well as likely abnormalities in glial cells. While genetic factors are important in the etiology of most mental disorders, the relatively high rates of discordance among identical twins, particularly for depression and other stress-related syndromes, clearly indicate the importance of additional mechanisms. Environmental factors such as stress are known to play a role in the onset of these illnesses. Exposure to such environmental insults induces stable changes in gene expression, neural circuit function, and ultimately behavior, and these maladaptations appear distinct between developmental versus adult exposures. Increasing evidence indicates that these sustained abnormalities are maintained by epigenetic modifications in specific brain regions. Indeed, transcriptional dysregulation and the aberrant epigenetic regulation that underlies this dysregulation is a unifying theme in psychiatric disorders. Here, we provide a progress report of epigenetic studies of the three major psychiatric syndromes, depression, schizophrenia, and bipolar disorder. We review the literature derived from animal models of these disorders as well as from studies of postmortem brain tissue from human patients. While epigenetic studies of mental illness remain at early stages, understanding how environmental factors recruit the epigenetic machinery within specific brain regions to cause lasting changes in disease susceptibility and pathophysiology is revealing new insight into the etiology and treatment of these conditions.
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Histone modifications play a central role in the epigenetic regulation of depression by influencing chromatin structure and transcriptional control.
“Histone modifications play a central role in the epigenetic regulation of depression by influencing chromatin structure and transcriptional control (Czarny et al., 2021; Nestler et al., 2016).”
From Histone modifications and depression: epigenetic mechanisms, therapeutic targets, and translational outlook (2026) · cites this paper as Nestler et al., 2016
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“Histone modifications play a central role in the epigenetic regulation of depression by influencing chromatin structure and transcriptional control (Czarny et al., 2021; Nestler et al., 2016).”
- Authors
- Nestler, E. J., Peña, C. J., Kundakovic, M., Mitchell, A., & Akbarian, S.
- Affiliations
- Icahn School of Medicine at Mount Sinai (US)
- Departments of Neuroscience and Psychiatry, The Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA
- Corresponding author
- Nestler, Eric J.
- Venue
- The Neuroscientist
- Publisher
- SAGE Publications
- Published
- 2016-07-09
- Volume
- 22
- Issue
- 5
- Pages
- 447-463
- ISSN
- 1073-8584 (ISSN-L)
- 1089-4098
- PMC
- PMC4826318
- OpenAlex
- W2340426429
- Cited by
- 342
- References
- 124
- Citations by year
- 2026: 28 · 2025: 33 · 2024: 28 · 2023: 25 · 2022: 29 · 2021: 38 · 2020: 35 · 2019: 39 · 2018: 31 · 2017: 26 · 2016: 29 · 2014: 1
- FWCI
- 12.45
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- The Neuroscientist (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Mental Health (P50MH096890)
- 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 › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- epigenetics, mental illness, depression, schizophrenia, bipolar disorder, environmental stress, gene expression regulation, transcriptional dysregulation, brain regions, animal models of psychiatric disorders, postmortem brain, glial cells, neural circuit function, disease susceptibility
- MeSH terms
- Animals, Brain, Humans, Schizophrenia, Gene Expression, DNA Methylation, MicroRNAs, Epigenesis, Genetic
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