Cited by 260Epigenetics and DNA MethylationTreatment of Major DepressionGenetic Associations and Epidemiology

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Epigenetic Aging in Major Depressive Disorder

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Han, Laura K.M., Aghajani, Moji, Clark, Shaunna L., Chan, Robin F., Hattab, Mohammad W., Shabalin, Andrey A., Zhao, Min, Kumar, Gaurav, Xie, Lin Ying, Jansen, Rick, Milaneschi, Yuri, Dean, Brian, Aberg, Karolina A., van den Oord, Edwin J.C.G., Penninx, Brenda W.J.H.·2018·American Journal of Psychiatry

DOI 10.1176/appi.ajp.2018.17060595PMC PMC6094380

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Abstract

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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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: Han, Laura K.M.
Aghajani, Moji
Clark, Shaunna L.
Chan, Robin F.
Hattab, Mohammad W.
Shabalin, Andrey A.
Zhao, Min
Kumar, Gaurav
Xie, Lin Ying
Jansen, Rick
Milaneschi, Yuri
Dean, Brian
Penninx, Brenda W.J.H.
Venue: American Journal of Psychiatry
Publisher: American Psychiatric Association Publishing
Published: 2018-08
Volume: 175
Issue: 8
Pages: 774-782
ISSN: 0002-953X (ISSN-L)
1535-7228
DOI: 10.1176/appi.ajp.2018.17060595
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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Epigenetic Aging in Major Depressive Disorder

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