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Epigenetic Aging in Major Depressive Disorder.

Laura K M Han1, Moji Aghajani1, Shaunna L Clark1

  • 1From 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.

The American Journal of Psychiatry
|April 17, 2018
PubMed
Summary

Major depressive disorder is linked to accelerated epigenetic aging, making individuals appear biologically older. This accelerated aging, measured by DNA methylation patterns, was also more pronounced with a history of childhood trauma.

Keywords:
Assay TechniquesGeneticsMood Disorders-Unipolar

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Area of Science:

  • Neuroscience
  • Genetics
  • Psychiatry

Background:

  • Major depressive disorder (MDD) is a significant risk factor for mortality and age-related diseases.
  • Epigenetic aging, indicated by DNA methylation (DNAm) patterns, offers a molecular clock to assess biological age.
  • Understanding the link between MDD and epigenetic aging is crucial for identifying therapeutic targets.

Purpose of the Study:

  • To investigate if major depression is associated with accelerated epigenetic aging in blood.
  • To determine if clinical characteristics of depression impact epigenetic aging.
  • To validate findings in postmortem brain tissue.

Main Methods:

  • DNAm age was calculated using methylation sites in blood from 811 depressed patients and 319 controls.
  • Epigenetic aging was quantified as residuals of DNAm age regressed on chronological age.
  • Replication was performed in postmortem brain samples (74 depressed, 64 controls).

Main Results:

  • Patients with major depression showed significantly higher epigenetic aging compared to controls (Cohen's d=0.18).
  • A dose-response relationship was observed between depression symptom severity and epigenetic aging.
  • Childhood trauma was positively associated with epigenetic aging in depressed individuals.

Conclusions:

  • Major depression is associated with accelerated epigenetic aging in both blood and brain tissue.
  • Individuals with MDD appear biologically older than their chronological age.
  • Childhood trauma exacerbates the effect of depression on epigenetic aging.