New insights into post-traumatic stress disorder (PTSD) reveal alterations in cellular communication within the prefrontal cortex involving inhibitory neurons, microglia, and other glial cells. Employing over two million single-nucleus RNA sequencing and ATAC-seq profiles from 111 human brain samples, the study identifies diminished somatostatin interneuron signaling and distinct neuroimmune interactions unique to PTSD compared to major depressive disorder. These findings, detailed in Nature, provide a refined understanding of the molecular and cell-type specific mechanisms driving persistent traumatic stress effects and highlight targeted pathways for therapeutic development.