Integration of neural and epigenetic contributions to posttraumatic stress symptoms: The role of hippocampal volume and glucocorticoid receptor gene methylation

PLoS One. 2018 Feb 7;13(2):e0192222. doi: 10.1371/journal.pone.0192222. eCollection 2018.


Many Veterans exposed to physical and psychological trauma experience symptoms of posttraumatic stress disorder (PTSD). As the etiology of PTSD symptoms is complex, a better understanding of the underlying biological mechanisms may improve preventative care and treatment for PTSD. Recent findings from the fields of neuroimaging and epigenetics offer important insights into the potential brain structures and biochemical pathways of modified gene expression associated with PTSD. We combined neuroimaging and epigenetic measures to assess current PTSD symptoms by measuring overall hippocampal volume and methylation of the glucocorticoid receptor (GR) gene (promoter region). Multiple regression analyses indicated that the hippocampal volume/GR methylation interaction was a predictor of PTSD symptoms. Our findings suggest that neuroimaging and epigenetic measures contribute interactively to PTSD symptoms. Incorporation of these metrics may aid in the identification and treatment of PTSD patients.

MeSH terms

  • Adult
  • DNA Methylation*
  • Epigenesis, Genetic*
  • Female
  • Hippocampus / pathology*
  • Humans
  • Male
  • Middle Aged
  • Receptors, Glucocorticoid / genetics*
  • Stress Disorders, Post-Traumatic / genetics
  • Stress Disorders, Post-Traumatic / pathology*


  • Receptors, Glucocorticoid

Grant support

WRIISC at the VA Palo Alto supported this project (