Cited by 277Epigenetics and DNA MethylationStress Responses and CortisolTreatment of Major Depression

Epigenetic Mechanisms of Depression and Antidepressant Action

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Vialou, Vincent, Feng, Jian, Robison, Alfred J., Nestler, Eric J.·2013·Annual Review of Pharmacology and Toxicology

Abstract

Epigenetic mechanisms, which control chromatin structure and function, mediate changes in gene expression that occur in response to diverse stimuli. Recent research has established that environmental events and behavioral experience induce epigenetic changes at particular gene loci and that these changes help shape neuronal plasticity and function and hence behavior. Some of these changes can be stable and can even persist for a lifetime. Increasing evidence supports the hypothesis that aberrations in chromatin remodeling and subsequent effects on gene expression within limbic brain regions contribute to the pathogenesis of depression and other stress-related disorders such as post-traumatic stress disorder and other anxiety syndromes. Likewise, the gradually developing but persistent therapeutic effects of antidepressant medications may be achieved in part via epigenetic mechanisms. This review discusses recent advances in our understanding of the epigenetic regulation of stress-related disorders and focuses on three distinct aspects of stress-induced epigenetic pathology: the effects of stress and antidepressant treatment during adulthood, the lifelong effects of early-life stress on subsequent stress vulnerability, and the possible transgenerational transmission of stress-induced abnormalities.

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Crossref · 10.1146/annurev-pharmtox-010611-134540

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  • In genetically susceptible models of treatment-resistant depression, SAHA inhibits HDAC2, restores histone acetylation and BDNF levels, and reverses antidepressant non-responsiveness.

    “In genetically susceptible models of treatment-resistant depression, SAHA inhibits HDAC2, restores histone acetylation and BDNF levels, and reverses antidepressant non-responsiveness (Meylan et al., 2016; Vialou et al., 2013).”

    From Histone modifications and depression: epigenetic mechanisms, therapeutic targets, and translational outlook (2026) · cites this paper as Vialou et al., 2013

    The section on histone acetylation in adult responses to stress reports antidepressant-like effects from HDAC inhibition and, separately, links antidepressant treatment to increased acetylation at the Bdnf promoter. It does not report that SAHA inhibits HDAC2 or restores BDNF in genetically susceptible, treatment-resistant models, nor that it reverses antidepressant non-responsiveness. No page number is available in our copy. (LLM, conf=0.88)

    Experimental — accuracy not yet measured
  • This risk-averse approach increases cognitive sensitivity to sensory cues of social risk.

    “This maintains that depressed mood reflects an adaptive, risk-averse approach to social interaction that reduces the likelihood of further aversive outcomes by: (1) increasing our cognitive sensitivity to (sensory) cues of social risk; (2) reducing our (behavioural) propensity for taking social risks; and (3) initiating signalling behaviours that elicit support and defuse conflict [32].”

    From The depressed brain: an evolutionary systems theory (2017) · cites this paper as [32]

  • This risk-averse approach reduces behavioural propensity for taking social risks.

    “This maintains that depressed mood reflects an adaptive, risk-averse approach to social interaction that reduces the likelihood of further aversive outcomes by: (1) increasing our cognitive sensitivity to (sensory) cues of social risk; (2) reducing our (behavioural) propensity for taking social risks; and (3) initiating signalling behaviours that elicit support and defuse conflict [32].”

    From The depressed brain: an evolutionary systems theory (2017) · cites this paper as [32]

  • This risk-averse approach initiates signalling behaviours that elicit support and defuse conflict.

    “This maintains that depressed mood reflects an adaptive, risk-averse approach to social interaction that reduces the likelihood of further aversive outcomes by: (1) increasing our cognitive sensitivity to (sensory) cues of social risk; (2) reducing our (behavioural) propensity for taking social risks; and (3) initiating signalling behaviours that elicit support and defuse conflict [32].”

    From The depressed brain: an evolutionary systems theory (2017) · cites this paper as [32]

  • Depressed mood reflects an adaptive, risk-averse approach to social interaction that reduces the likelihood of further aversive outcomes.

    “This maintains that depressed mood reflects an adaptive, risk-averse approach to social interaction that reduces the likelihood of further aversive outcomes by: (1) increasing our cognitive sensitivity to (sensory) cues of social risk; (2) reducing our (behavioural) propensity for taking social risks; and (3) initiating signalling behaviours that elicit support and defuse conflict [32].”

    From The depressed brain: an evolutionary systems theory (2017) · cites this paper as [32]

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Authors
Vialou, V., Feng, J., Robison, A. J., & Nestler, E. J.
Affiliations
Icahn School of Medicine at Mount Sinai (US)
Corresponding author
Nestler, Eric J.
Venue
Annual Review of Pharmacology and Toxicology
Published
2013-01-06
Volume
53
Issue
1
Pages
59-87
ISSN
  • 0362-1642 (ISSN-L)
  • 1545-4304
OpenAlex
W2130374405
Cited by
277
References
216
Citations by year
2026: 9 · 2025: 9 · 2024: 12 · 2023: 11 · 2022: 13 · 2021: 18 · 2020: 14 · 2019: 26 · 2018: 26 · 2017: 25 · 2016: 32 · 2015: 32 · 2014: 26 · 2013: 21 · 2012: 3
FWCI
1.45
Type
journal article
Language
en
Open access
Locations
  • The Annual Review of Pharmacology and Toxicology (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
National Institute of Mental Health (P50MH096890, R01MH051399)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
  • Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
  • Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
Keywords
epigenetics, depression, antidepressant mechanism, chromatin remodeling, neuroplasticity, limbic system, post-traumatic stress disorder, anxiety, early life stress, stress vulnerability, transgenerational transmission, gene expression regulation
MeSH terms
Animals, Antidepressive Agents, Depression, Humans, Gene Expression, DNA Methylation, Epigenesis, Genetic

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