Post-traumatic stress disorder(PTSD)remains a debilitating psychiatric condition with limited pharmacological treatment options.Identifying novel therapeutic targets is critical for addressing its unmet clinical needs...Post-traumatic stress disorder(PTSD)remains a debilitating psychiatric condition with limited pharmacological treatment options.Identifying novel therapeutic targets is critical for addressing its unmet clinical needs.Through our comprehensive human clinical research,including both cross-sectional and longitudinal studies,we revealed a compelling link between dysregulated prefrontal gamma-aminobutyric acid(GABA)levels and PTSD symptoms.Notably,elevated prefrontal GABA levels in PTSD patients are associated with impaired cerebral blood flow(CBF)and symptom severity,normalizing with recovery,highlighting GABA dysregulation as a key mechanism in the disorder.Postmortem and PTSD-like mouse models implicated monoamine oxidase B(MAOB)-dependent astrocytic GABA as a primary driver of this imbalance,exacerbating deficit in fear extinction retrieval.展开更多
基金supported by National Research Foundation of Korea grants funded by the Ministry of Science and ICT(RS-2024-00457381 to I.K.L.2020M3E5D9079742 to H.R.)+2 种基金by the Ministry of Education(2020R1A6A1A03043528 to I.K.L.)This work was also in part supported by the Institute for Basic Science(IBS),Center for Cognition and Sociality(IBS-R001-D2 to C.J.L)This project applied tools developed under NIH grants R01 EB016089,R01 EB023963 and P41 EB031771.
文摘Post-traumatic stress disorder(PTSD)remains a debilitating psychiatric condition with limited pharmacological treatment options.Identifying novel therapeutic targets is critical for addressing its unmet clinical needs.Through our comprehensive human clinical research,including both cross-sectional and longitudinal studies,we revealed a compelling link between dysregulated prefrontal gamma-aminobutyric acid(GABA)levels and PTSD symptoms.Notably,elevated prefrontal GABA levels in PTSD patients are associated with impaired cerebral blood flow(CBF)and symptom severity,normalizing with recovery,highlighting GABA dysregulation as a key mechanism in the disorder.Postmortem and PTSD-like mouse models implicated monoamine oxidase B(MAOB)-dependent astrocytic GABA as a primary driver of this imbalance,exacerbating deficit in fear extinction retrieval.
