Epigenetic and immune function profiles associated with posttraumatic stress disorder

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 i...

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Published inProceedings of the National Academy of Sciences - PNAS Vol. 107; no. 20; pp. 9470 - 9475
Main Authors Uddin, Monica, Aiello, Allison E, Wildman, Derek E, Koenen, Karestan C, Pawelec, Graham, de los Santos, Regina, Goldmann, Emily, Galea, Sandro
Format Journal Article
LanguageEnglish
Published United States National Academy of Sciences 18.05.2010
National Acad Sciences
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Summary: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 from an ongoing, prospective epidemiologic study in Detroit, the Detroit 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 overrepresented 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 herpesvirus 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 downstream alterations in immune function by reducing methylation levels of immune-related genes.
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Author contributions: M.U., A.E.A., D.E.W., K.C.K., G.P., and S.G. designed research; M.U., R.d.l.S., E.G., and S.G. performed research; D.E.W. contributed new reagents/analytic tools; M.U., A.E.A., D.E.W., K.C.K., R.d.l.S., E.G., and S.G. analyzed data; and M.U., A.E.A., D.E.W., K.C.K., G.P., R.d.l.S., and S.G. wrote the paper.
Edited by Burton H. Singer, Princeton University, Princeton, NJ, and approved April 1, 2010 (received for review September 21, 2009)
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.0910794107