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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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Information & Authors

Information

Published In

Go to American Journal of Psychiatry
Go to American Journal of Psychiatry
American Journal of Psychiatry
Pages: 774 - 782
PubMed: 29656664

History

Received: 1 June 2017
Revision received: 1 December 2017
Revision received: 7 February 2018
Accepted: 20 February 2018
Published online: 16 April 2018
Published in print: August 01, 2018

Keywords

  1. Mood Disorders-Unipolar
  2. Assay Techniques
  3. Genetics

Authors

Details

Laura K.M. Han, M.Sc. [email protected]
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.
Moji Aghajani, Ph.D.
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.
Shaunna L. Clark, Ph.D.
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.
Robin F. Chan, Ph.D.
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.
Mohammad W. Hattab, Ph.D.
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.
Andrey A. Shabalin, Ph.D.
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.
Min Zhao, D.D.S.
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.
Gaurav Kumar, Ph.D.
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.
Lin Ying Xie, M.Sc.
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.
Rick Jansen, Ph.D.
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.
Yuri Milaneschi, Ph.D.
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.
Brian Dean, Ph.D.
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.
Karolina A. Aberg, Ph.D.
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.
Edwin J.C.G. van den Oord, Ph.D.
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.
Brenda W.J.H. Penninx, Ph.D.
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.

Notes

Address correspondence to Ms. Han ([email protected]).

Competing Interests

Dr. Penninx has received research funding from Janssen Research and Boehringer Ingelheim. The other authors report no financial relationships with commercial interests.

Funding Information

ZonMw10.13039/501100001826: 10-000-1002
National Institute of Mental Health10.13039/100000025: R01MH099110
The Netherlands Study of Depression and Anxiety (www.nesda.nl) is funded through the Geestkracht program of the Netherlands Organization for Health Research and Development (Zon-MW, grant 10-000-1002) and participating universities and mental health care organizations (VU University Medical Center, GGZ inGeest, Arkin, Leiden University Medical Center, GGZ Rivierduinen, University Medical Center Groningen, Lentis, GGZ Friesland, GGZ Drenthe). This work was supported by NIMH grant R01MH099110 and the EMGO+ Travel Grant. Brain tissue was received from four brain banks: the Victorian Brain Bank, supported by the Florey Institute of Neuroscience and Mental Health and the Alfred and Victorian Forensic Institute of Medicine and funded by Australia’s National Health and Medical Research Council and Parkinson’s Victoria; the Stanley Medical Research Institute; the Netherlands Brain Bank, Netherlands Institute of Neuroscience, Amsterdam; and the Harvard Brain Tissue Resource Center.

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