Fig. 1
Overview of study design and aims. a The first part of this research consisted of two comprehensive human clinical studies aimed at examining alterations in prefrontal GABA levels and their clinical implications in PTSD. Cross-sectional clinical study analyzed a cohort of 248 participants, divided into groups of persistent PTSD (N = 78), recovered PTSD (N = 84), and healthy control (N = 86), to investigate prefrontal GABA alterations in PTSD and their impact on CBF and clinical symptoms. Longitudinal clinical study involved 126 participants, including a trauma-exposed group (N = 65) and a healthy control group (N = 61), to study the reversibility of prefrontal GABA alterations as PTSD symptoms improved over time. b The second part of this research explored the therapeutic potential and underlying cellular mechanisms of interventions targeting prefrontal GABA inhibition for PTSD treatment. Postmortem human brain study focused on elucidating the cellular mechanisms underlying prefrontal GABA alterations in PTSD through the analysis of postmortem human brain tissues. PTSD mouse model study utilized a PTSD-like animal model to evaluate the aberrant astrocytic GABA homeostasis, confirming the consistency with humans. Genetic mouse model study investigated the potential benefits of genetically inhibiting MAOB to facilitate fear extinction in PTSD mouse models, suggesting implications for therapeutic strategies. PTSD mouse model study with KDS2010 treatment utilized a PTSD-like mouse model to evaluate the therapeutic efficacy of KDS2010, a reversible, selective MAOB inhibitor, in treating PTSD by modulating prefrontal GABA synthesis pathways. PTSD post-traumatic stress disorder, GABA gamma-aminobutyric acid, 1H-MRS proton magnetic resonance spectroscopy, ASL arterial spin labeling, CBF cerebral blood flow, MAOB monoamine oxidase B, ABAT 4-aminobutyrate aminotransferase
