Stem cell-derived neurons from combat veterans with post-traumatic stress disorder (PTSD) react differently to a stress hormone than those from veterans without PTSD, a finding that could provide insights into how genetics can make someone more susceptible to developing PTSD following trauma exposure.
This study was the first to use induced pluripotent stem cell models to study PTSD. Specifically, the research team studied a cohort of 39 combat veterans with and without PTSD who were recruited from the James J Peters Veterans Affairs Medical Center in the Bronx. Veterans underwent skin biopsies and their skin cells were reprogrammed into induced pluripotent stem cells (iPSC).To mimic the stress response that triggers PTSD, the scientists exposed the iSPC-derived neurons to the stress hormone hydrocortisone, a synthetic version of the body’s own cortisol that is used as part of the “fight-or-flight” response. Using gene expression profiling and imaging, the scientists found that neurons from individuals with PTSD were hypersensitive to this pharmacological trigger. The team’s gene expression analysis revealed a set of genes that were particularly active in PTSD-prone neurons following their exposure to stress hormones. Moreover, the distinctions between how PTSD and non-PTSD cells responded to stress could be informative in predicting which individuals are at higher risk for PTSD.
The researchers plan to continue leveraging their induced pluripotent stem cell models to further investigate the genetic risk factors pinpointed by this study and to study how PTSD affects other types of brain cells, helping to broaden opportunities for therapeutic discovery.