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Epigenetic Aging in Major Depressive Disorder
Open accessAbstract
OBJECTIVE: Major depressive disorder is associated with an increased risk of mortality and aging-related diseases. The authors examined whether major depression is associated with higher epigenetic aging in blood as measured by DNA methylation (DNAm) patterns, whether clinical characteristics of major depression have a further impact on these patterns, and whether the findings replicate in brain tissue. METHOD: DNAm age was estimated using all methylation sites in blood of 811 depressed patients and 319 control subjects with no lifetime psychiatric disorders and low depressive symptoms from the Netherlands Study of Depression and Anxiety. The residuals of the DNAm age estimates regressed on chronological age were calculated to indicate epigenetic aging. Major depression diagnosis and clinical characteristics were assessed with questionnaires and psychiatric interviews. Analyses were adjusted for sociodemographic characteristics, lifestyle, and health status. Postmortem brain samples of 74 depressed patients and 64 control subjects were used for replication. Pathway enrichment analysis was conducted using ConsensusPathDB to gain insight into the biological processes underlying epigenetic aging in blood and brain. RESULTS: Significantly higher epigenetic aging was observed in patients with major depression compared with control subjects (Cohen's d=0.18), with a significant dose effect with increasing symptom severity in the overall sample. In the depression group, epigenetic aging was positively and significantly associated with childhood trauma score. The case-control difference was replicated in an independent data set of postmortem brain samples. The top significantly enriched Gene Ontology terms included neuronal processes. CONCLUSIONS: As compared with control subjects, patients with major depression exhibited higher epigenetic aging in blood and brain tissue, suggesting that they are biologically older than their corresponding chronological age. This effect was even more profound in the presence of childhood trauma.
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“Increased epigenetic aging has also found to be associated with the categorical phenotype of major depression (Han et al., 2018).”
From The applied implications of epigenetics in anxiety, affective and stress-related disorders - A review and synthesis on psychosocial stress, psychotherapy and prevention (2020) · cites this paper as Han et al., 2018
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“For example, elevated DNA methylation of a gene important for neuronal development (BDNF) 4,24 and increased biological age estimated from a defined selection of DNA methylation loci have been observed in individuals with various psychopathologies.12,25”
From The role of epigenetics in psychological resilience (2021) · cites this paper as [12]
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“Depression predisposes to medical illnesses and advances biological aging indicated by shorter telomere length, accelerated brain aging and advanced epigenetic aging.”
From Mechanisms and treatment of late-life depression (2019) · cites this paper as [1]
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Metadata
- Authors
- Han, L. K. M., Aghajani, M., Clark, S. L., Chan, R. F., Hattab, M. W., Shabalin, A. A., Zhao, M., Kumar, G., Xie, L. Y., Jansen, R., Milaneschi, Y., Dean, B., Aberg, K. A., van den Oord, E. J. C. G., & Penninx, B. W. J. H.
- Affiliations
- Virginia Commonwealth University (US)
- From the Department of Psychiatry, VU University Medical Center, Amsterdam Neuroscience, GGZ inGeest, the Amsterdam Public Health Research Institute, Amsterdam; the Center for Biomarker Research and Precision Medicine, School of Pharmacy, Virginia Commonwealth University, Richmond; the Molecular Psychiatry Laboratory, Florey Department of Neuroscience and Mental Health, Melbourne, Australia; and the Centre for Mental Health, Faculty of Health, Arts, and Design, Swinburne University, Hawthorne, Australia.
- ORCID
- Venue
- American Journal of Psychiatry
- Published
- 2018-08
- Volume
- 175
- Issue
- 8
- Pages
- 774-782
- ISSN
- 0002-953X (ISSN-L)
- 1535-7228
- PMC
- PMC6094380
- OpenAlex
- W2800301228
- Semantic Scholar
- 355446f30616b5d634e9a6e0adea4204848aa234
- Cited by
- 260
- References
- 54
- Citations by year
- 2026: 28 · 2025: 30 · 2024: 39 · 2023: 33 · 2022: 36 · 2021: 37 · 2020: 22 · 2019: 29 · 2018: 4
- FWCI
- 8.18
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- American Journal of Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Pure Amsterdam UMC (publishedVersion, other-oa)
- Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Minerva Access (University of Melbourne) (submittedVersion)
- Swinburne figshare (Swinburne University of Technology) (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Funders
- Stanley Medical Research Institute
- Victorian Brain Bank
- Medical Research Council
- National Health and Medical Research Council
- National Institute on Alcohol Abuse and Alcoholism (R01AA026057, K01AA021266)
- National Institute of Mental Health (R01MH099110)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Keywords
- major depressive disorder, epigenetic aging, DNA methylation, childhood trauma, symptom severity, postmortem brain, blood DNA methylation, neural processes, age-related diseases
- MeSH terms
- Adult Survivors of Child Adverse Events, Adult, Aging, Brain, Major Depressive Disorder, Female, Health Status, Humans, Life Style, Longitudinal Studies, Male, Netherlands, Case-Control Studies, DNA Methylation
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