Interrogation of Million Veteran Program data reveals associations between post-traumatic stress disorder and autoimmune and other immune-mediated inflammatory diseases 3945

Abstract Description Post-traumatic stress disorder (PTSD), a psychiatric condition caused by exposure to a highly traumatic event, is characterized by intrusive thoughts, negative cognitions, and hyperarousal. While often considered purely psychological, recent work suggests immune involvement in PTSD pathogenesis, with noted increases in autoimmune diseases like systemic lupus erythematosus (SLE) and rheumatoid arthritis, as well as increases in inflammatory cytokines IL-1β and interferon (IFN) gamma. Accordingly, we performed a large-scale interrogation for the association of PTSD with autoimmune diseases using data from the Million Veteran Program (MVP). Using PheCodes, groupings of clinical phenotypes according to ICD-9/10 codes, we analyzed 67 immune-related conditions in PTSD and non-PTSD subjects using chi-squared analysis. Many of these conditions achieved Bonferroni-corrected significance (p < 7.5x10-4), including SLE (OR = 1.37, p = 7.76x10-14), Sjögren’s syndrome (OR = 1.54, p = 6.12x10-72), and Hashimoto’s disease (OR = 1.45, p = 2.19x10-11). In total, 26 conditions were increased while 4 were decreased in those with PTSD compared to non-PTSD subjects. Notably, many conditions showing association with PTSD have well-defined IFN signatures or involvement of IFN-related pathways in disease pathogenesis. These associations between PTSD and inflammatory/autoimmune-mediated diseases suggest dysregulation of overlapping pathogenic pathways potentially linked by IFNs and warrants deeper investigation. Funding Sources VA Award MVP058 Topic Categories Translational and Interventional Immunology (TI)