Neurobiology of psychiatric disorders

Publication date: 18/06/2025

Authors: Hwang, A., Skarica, M., Xu, S. et al.

Journal: Nature

Commentary: A recent landmark study published in Nature offers an unprecedented cell-type-specific molecular characterization of post-traumatic stress disorder (PTSD) in the human dorsolateral prefrontal cortex (DLPFC), a brain region critically involved in the regulation of stress and implicated in PTSD. By analyzing post-mortem brain tissue from individuals with and without PTSD and major depressive disorder (MDD), the researchers identified distinct changes in gene expression and epigenetic regulation across both neuronal and non-neuronal cell types. They found alterations in genes and pathways associated with PTSD, including those related to glucocorticoid signaling, immune and neuroinflammatory responses, and neurotransmitters, especially GABA. Notably, the most pronounced gene expression changes were observed in endothelial cells, suggesting a potential underexplored role for the brain vasculature in PTSD pathology. Through the integration of genetic, transcriptomic, and epigenetic data, the study also revealed that specific genetic variants may disrupt the regulation of key brain genes (e.g., ELFN1, MAD1L1, and KCNIP4), providing new insight into the molecular basis of PTSD and related psychiatric conditions.

Commented by: Giulia Federica Mancini (08/07/2025)

DOI: https://doi.org/10.1038/s41586-025-09083-y