A Proteome-wide, Multi-Omics Analysis Implicates Novel Protein Dysregulation in Post-Traumatic Stress Disorder

Post-traumatic stress disorder (PTSD) is a common and disabling psychiatric disorder. Here we present findings from the first proteome-wide study of the postmortem PTSD brain. We performed tandem mass spectrometry on large cohort of donors (N = 66) in two prefrontal cortical areas and found differentially expressed proteins and co-expression modules disturbed in PTSD. Integrative analysis pointed to hsa-mir-589 as a regulatory miRNA responsible for disruptions in neuronal protein networks for PTSD, including the GABA vesicular transporter, SLC32A1. In addition, we identified significant enrichment of risk genes for Alzheimer’s Disease (N= 94,403), major depression (N = 807,553), and schizophrenia (N = 35,802) within PTSD co-expression protein modules, suggesting shared molecular pathology. Our findings highlight the altered proteomic landscape of postmortem PTSD brain and provide a novel framework for future studies integrating proteomic profiling with transcriptomics in postmortem human brain tissue.