Epigenetics and depressive disorders: a review of current progress and future directions
Abstract
BACKGROUND: Several broad lines of evidence support the involvement of epigenetic processes in neurodevelopment and psychiatric disorders. Epigenetic disruption also provides a potential mechanism to account for the numerous gene-environment interactions that have been reported in association with neuropsychiatric phenotypes. METHODS: A review of the literature was performed with keywords 'depression', 'depressive disorder' or 'antidepressants' and 'DNA methylation', or 'epigenetics' in humans. Citations were limited to those written in English and published prior to July 2014. RESULTS: We present a summary of results to date. Most studies have focused on DNA methylation in various CNS or peripheral tissue, with almost universally small sample sizes. Although seven epigenome-wide association studies have now been reported, the majority of studies have used a candidate-gene approach. Three genes (SLC6A4, BDNF, NR3C1) have been investigated in more than one study, but replication of findings is generally lacking. CONCLUSIONS: Recent evidence provides insights to epigenetic processes in psychiatric disorders; however, replication is lacking and care must be taken in the interpretation of current findings. This applies to epigenetic epidemiology generally, which is subject to various limitations that no single approach can address in isolation. Due to limited focus of most depression studies to date, placing the findings within the broader context of mood disorder pathophysiology may prove challenging. However, identifying peripheral biomarkers for depressive disorder remains a tantalising possibility, especially given the potential for carefully-designed longitudinal studies with multiple biospecimens and ongoing advances in epigenetic technologies.
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Epigenetic disruption has been implicated in cancer, aging, and a range of complex diseases, including psychiatric disorders such as depression and PTSD.
“Epigenetic disruption has been clearly implicated in cancer, aging, and a range of complex diseases, including psychiatric disorders, such as depression [33] and PTSD [34,35].”
The usefulness of peripheral epigenetic markers in complex neurobiological phenotypes and brain disorders is now well-recognized.
“Conversely, the usefulness of peripheral epigenetic markers in complex neurobiological phenotypes and brain disorders is now well-recognized [33].”
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Self-citation
- Authors
- Januar, V., Saffery, R., & Ryan, J.
- Affiliations
- The University of Melbourne (AU)
- Inserm (FR)
- Venue
- International Journal of Epidemiology
- Publisher
- Oxford University Press (OUP)
- Published
- 2015-02-24
- Volume
- 44
- Issue
- 4
- Pages
- 1364-1387
- ISSN
- 0300-5771 (ISSN-L)
- 1464-3685
- OpenAlex
- W2109270323
- Cited by
- 99
- References
- 34
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 10 · 2023: 10 · 2022: 8 · 2021: 8 · 2020: 9 · 2019: 11 · 2018: 7 · 2017: 15 · 2016: 9 · 2015: 4 · 2014: 1
- FWCI
- 1.13
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- International Journal of Epidemiology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Keywords
- epigenetics, depression, DNA methylation, gene-environment interaction, epigenome-wide association study, serotonin transporter, brain-derived neurotrophic factor, NR3C1, antidepressants, mood disorders, peripheral biomarkers, brain development
- MeSH terms
- Animals, Depression, Major Depressive Disorder, Depressive Disorder, Major, Disease Models, Animal, Humans, Receptors, Glucocorticoid, Biomarkers, DNA Methylation, Brain-Derived Neurotrophic Factor, Epigenesis, Genetic, Serotonin Plasma Membrane Transport Proteins, Gene-Environment Interaction
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