@article{836,
  author = {Carina Seah and Michael S. Breen and Tom Rusielewicz and Heather N. Bader and Changxin Xu and Christopher J. Hunter and Barry McCarthy and P. J. Michael Deans and Mitali Chattopadhyay and Jordan Goldberg and Frank Desarnaud and Iouri Makotkine and Janine D. Flory and Linda M. Bierer and Migle Staniskyte and NYSCF Global Stem Cell Array® Team and Lauren Bauer and Katie Brenner and Geoff Buckley-Herd and Sean DesMarteau and Patrick Fenton and Peter Ferrarotto and Jenna Hall and Selwyn Jacob and Travis Kroeker and Gregory Lallos and Hector Martinez and Paul McCoy and Frederick J. Monsma and Dorota Moroziewicz and Reid Otto and Kathryn Reggio and Bruce Sun and Rebecca Tibbets and Dong Woo Shin and Hongyan Zhou and Matthew Zimmer and Scott A. Noggle and Laura M. Huckins and Daniel Paull and Kristen J. Brennand and Rachel Yehuda},
  title = {Modeling gene × environment interactions in PTSD using human neurons reveals diagnosis-specific glucocorticoid-induced gene expression},
  abstract = {Abstract
            
              Post-traumatic stress disorder (PTSD) can develop following severe trauma, but the extent to which genetic and environmental risk factors contribute to individual clinical outcomes is unknown. Here, we compared transcriptional responses to hydrocortisone exposure in human induced pluripotent stem cell (hiPSC)-derived glutamatergic neurons and peripheral blood mononuclear cells (PBMCs) from combat veterans with PTSD (
              n
               = 19 hiPSC and
              n
               = 20 PBMC donors) and controls (
              n
               = 20 hiPSC and
              n
               = 20 PBMC donors). In neurons only, we observed diagnosis-specific glucocorticoid-induced changes in gene expression corresponding with PTSD-specific transcriptomic patterns found in human postmortem brains. We observed glucocorticoid hypersensitivity in PTSD neurons, and identified genes that contribute to this PTSD-dependent glucocorticoid response. We find evidence of a coregulated network of transcription factors that mediates glucocorticoid hyper-responsivity in PTSD. These findings suggest that induced neurons represent a platform for examining the molecular mechanisms underlying PTSD, identifying biomarkers of stress response, and conducting drug screening to identify new therapeutics.},
  year = {11},
  journal = {Nature Neuroscience},
  volume = {25},
  pages = {1434-1445},
  month = {11/2022},
  issn = {1097-6256, 1546-1726},
  url = {https://www.nature.com/articles/s41593-022-01161-y},
  doi = {10.1038/s41593-022-01161-y},
  language = {en},
}