Posttraumatic psychopathology and the pace of the epigenetic clock: a longitudinal investigation

Psychol Med. 2019 Apr;49(5):791-800. doi: 10.1017/S0033291718001411. Epub 2018 Jun 13.

Abstract

Background: Posttraumatic stress disorder (PTSD) and stress/trauma exposure are cross-sectionally associated with advanced DNA methylation age relative to chronological age. However, longitudinal inquiry and examination of associations between advanced DNA methylation age and a broader range of psychiatric disorders is lacking. The aim of this study was to examine if PTSD, depression, generalized anxiety, and alcohol-use disorders predicted acceleration of DNA methylation age over time (i.e. an increasing pace, or rate of advancement, of the epigenetic clock).

Methods: Genome-wide DNA methylation and a comprehensive set of psychiatric symptoms and diagnoses were assessed in 179 Iraq/Afghanistan war veterans who completed two assessments over the course of approximately 2 years. Two DNA methylation age indices (Horvath and Hannum), each a weighted index of an array of genome-wide DNA methylation probes, were quantified. The pace of the epigenetic clock was operationalized as change in DNA methylation age as a function of time between assessments.

Results: Analyses revealed that alcohol-use disorders (p = 0.001) and PTSD avoidance and numbing symptoms (p = 0.02) at Time 1 were associated with an increasing pace of the epigenetic clock over time, per the Horvath (but not the Hannum) index of cellular aging.

Conclusions: This is the first study to suggest that posttraumatic psychopathology is longitudinally associated with a quickened pace of the epigenetic clock. Results raise the possibility that accelerated cellular aging is a common biological consequence of stress-related psychopathology, which carries implications for identifying mechanisms of stress-related cellular aging and developing interventions to slow its pace.

Keywords: Alcohol-use disorders; DNA methylation age; Epigenetic age; PTSD; longitudinal.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adult
  • Cellular Senescence*
  • Cross-Sectional Studies
  • DNA Methylation*
  • Epigenesis, Genetic*
  • Female
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study
  • Humans
  • Longitudinal Studies
  • Male
  • Psychopathology*
  • Regression Analysis
  • Stress Disorders, Post-Traumatic / genetics*
  • Stress Disorders, Post-Traumatic / psychology
  • Trauma Severity Indices
  • United States
  • United States Department of Veterans Affairs
  • Young Adult