Epigenetic and immune function profiles associated with posttraumatic stress disorder

Monica Uddin, Allison E. Aiello, Derek E. Wildman, Karestan C. Koenen, Graham Pawelec, Regina De Los Santos, Emily Goldmann, Sandro Galea

Research output: Contribution to journalArticlepeer-review

Abstract

The biologic underpinnings of posttraumatic stress disorder (PTSD) have not been fully elucidated. Previous work suggests that alterations in the immune system are characteristic of the disorder. Identifying the biologic mechanisms by which such alterations occur could provide fundamental insights into the etiology and treatment of PTSD. Here we identify specific epigenetic profiles underlying immune system changes associated with PTSD. Using blood samples (n = 100) obtained froman ongoing, prospective epidemiologic study in Detroit, theDetroit Neighborhood Health Study, we applied methylation microarrays to assay CpG sites from more than 14,000 genes among 23 PTSD-affected and 77 PTSD-unaffected individuals. We show that immune system functions are significantly over represented among the annotations associated with genes uniquely unmethylated among those with PTSD. We further demonstrate that genes whose methylation levels are significantly and negatively correlated with traumatic burden show a similar strong signal of immune function among the PTSD affected. The observed epigenetic variability in immune function by PTSD is corroborated using an independent biologic marker of immune response to infection, CMV - a typically latent herpes virus whose activity was significantly higher among those with PTSD. This report of peripheral epigenomic and CMV profiles associated with mental illness suggests a biologic model of PTSD etiology in which an externally experienced traumatic event induces down stream alterations in immune function by reducing methylation levels of immune-related genes.

Original languageEnglish (US)
Pages (from-to)9470-9475
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume107
Issue number20
DOIs
StatePublished - May 18 2010

Keywords

  • Cumulative trauma
  • Cytomegalovirus
  • Epidemiology
  • Methylation
  • Psychiatry

ASJC Scopus subject areas

  • General

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