03151nas a2200649   4500000000100000000000100001008004000002260001200042100001600054700002100070700002000091700002100111700001600132700002600148700001900174700002400193700002500217700002000242700002000262700002000282700002000302700002000322700002100342700004000363700001700403700001800420700002300438700002000461700001900481700002100500700001500521700001700536700001900553700001900572700002000591700001500611700002400626700002300650700001400673700001900687700001400706700002000720700001800740700001700758700001900775700002000794700002100814700001700835700002400852700001800876245014000894856005501034300001401089490000701103520136601110022002502476       11                             d  c11/20221 aCarina Seah1 aMichael S. Breen1 aTom Rusielewicz1 aHeather N. Bader1 aChangxin Xu1 aChristopher J. Hunter1 aBarry McCarthy1 aP. J. Michael Deans1 aMitali Chattopadhyay1 aJordan Goldberg1 aFrank Desarnaud1 aIouri Makotkine1 aJanine D. Flory1 aLinda M. Bierer1 aMigle Staniskyte1 aNYSCF Global Stem Cell Array® Team1 aLauren Bauer1 aKatie Brenner1 aGeoff Buckley-Herd1 aSean DesMarteau1 aPatrick Fenton1 aPeter Ferrarotto1 aJenna Hall1 aSelwyn Jacob1 aTravis Kroeker1 aGregory Lallos1 aHector Martinez1 aPaul McCoy1 aFrederick J. Monsma1 aDorota Moroziewicz1 aReid Otto1 aKathryn Reggio1 aBruce Sun1 aRebecca Tibbets1 aDong Woo Shin1 aHongyan Zhou1 aMatthew Zimmer1 aScott A. Noggle1 aLaura M. Huckins1 aDaniel Paull1 aKristen J. Brennand1 aRachel Yehuda00aModeling gene × environment interactions in PTSD using human neurons reveals diagnosis-specific glucocorticoid-induced gene expression  uhttps://www.nature.com/articles/s41593-022-01161-y  a1434-14450 v253 aAbstract
            
              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.  a1097-6256, 1546-1726