Expression and methylation in posttraumatic stress disorder and resilience; evidence of a role for odorant receptors

Post-traumatic stress disorder (PTSD) is a common and potentially disabling disorder that develops in 1/5 to 1/3 of people exposed to severe trauma. Twin studies indicate that genetic factors account for at least one third of the variance in the risk for developing PTSD, however, the specific role for genetic factors in the pathogenesis of PTSD is not well understood. We studied genome-wide gene expression and DNA methylation profiles in 12 participants with PTSD and 12 participants who were resilient to similar severity trauma exposure. Close to 4000 genes were differentially expressed with adjusted p<0.05, fold-change >2, with all but 3 upregulated with PTSD. Eight odorant/olfactory receptor related genes were up-regulated with PTSD as well as genes related to immune activation, the Gamma-Aminobutyric Acid A (GABAA) receptor, and vitamin D synthesis. No differences with adjusted significance for DNA methylation were found. We conclude that increased gene expression may play an important role in PTSD and this expression may not be a consequence of DNA methylation. The role of odorant receptor expression warrants independent replication.