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Author Notes:

To whom correspondence should be addressed. E-mail: mehta@mpipsykl.mpg.de

Author contributions: B.B., K.J.R., and E.B.B. designed research; D.M., T.K., A.K.S., T.W.P., M.R.-H., A.L., and K.B.M. performed research; D.M., K.N.C., A.A., M.G., and B.M.-M. analyzed data; and D.M., T.K., K.N.C., A.K.S., A.A., T.W.P., M.R.-H., A.L., M.G., K.B.M., B.B., B.M.-M., K.J.R., and E.B.B. wrote the paper.

The authors thank Maik Koedel and members of the Grady Trauma Project at Emory—particularly Allen Graham, Kimberly Kerley, Jennifer Davis, Angelo Brown, Alicia Nelson, Jennifer Winkler, Will Holland, Sarah Spann, Kimberly Dement, Dana Goodenough, and Emily Reiser—for excellent technical assistance.

Conflict of interest statement: K.J.R. has an unrelated role as cofounder of Extinction Pharmaceuticals for development of N-methyl-d-aspartate-based therapeutics.

Subjects:

Research Funding:

This work was supported by the Max-Planck Society; the Behrens-Weise Foundation (E.B.B.); National Institute of Mental Health Grants MH071537 (to K.J.R.) and MH085806 (to A.K.S.); and the Burroughs Wellcome Fund.

Keywords:

  • Science & Technology
  • Multidisciplinary Sciences
  • Science & Technology - Other Topics
  • epigenome
  • biomarkers
  • psychiatry
  • development
  • DNA METHYLATION
  • GLUCOCORTICOID-RECEPTOR
  • RISK-FACTORS
  • TRAUMA
  • DEPRESSION
  • INFLAMMATION
  • LIFE
  • ABUSE
  • GENE
  • EXPOSURE

Childhood maltreatment is associated with distinct genomic and epigenetic profiles in posttraumatic stress disorder

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Journal Title:

Proceedings of the National Academy of Sciences

Volume:

Volume 110, Number 20

Publisher:

, Pages 8302-8307

Type of Work:

Article | Final Publisher PDF

Abstract:

Childhood maltreatment is likely to influence fundamental biological processes and engrave long-lasting epigenetic marks, leading to adverse health outcomes in adulthood. We aimed to elucidate the impact of different early environment on disease-related genomewide gene expression and DNA methylation in peripheral blood cells in patients with posttraumatic stress disorder (PTSD). Compared with the same trauma-exposed controls (n = 108), geneexpression profiles of PTSD patients with similar clinical symptoms and matched adult trauma exposure but different childhood adverse events (n = 32 and 29) were almost completely nonoverlapping (98%). These differences on the level of individual transcripts were paralleled by the enrichment of several distinct biological networks between the groups. Moreover, these gene-expression changes were accompanied and likely mediated by changes in DNA methylation in the same loci to a much larger proportion in the childhood abuse (69%) vs. the non-child abuse-only group (34%). This study is unique in providing genome-wide evidence of distinct biological modifications in PTSD in the presence or absence of exposure to childhood abuse. The findings that nonoverlapping biological pathways seem to be affected in the two PTSD groups and that changes inDNA methylation appear to have a much greater impact in the childhood-abuse group might reflect differences in the pathophysiology of PTSD, in dependence of exposure to childhood maltreatment. These results contribute to a better understanding of the extent of influence of differences in trauma exposure on pathophysiological processes in stress-related psychiatric disorders and may have implications for personalized medicine.

Copyright information:

NATIONAL ACADEMY OF SCIENCES / PROCEEDINGS

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