Molecular linkage between post-traumatic stress disorder and cognitive impairment: a targeted proteomics study of World Trade Center responders

Existing work on proteomics has found common biomarkers that are altered in individuals with post-traumatic stress disorder (PTSD) and mild cognitive impairment (MCI). The current study expands our understanding of these biomarkers by profiling 276 plasma proteins with known involvement in neurobiological processes using the Olink Proseek Multiplex Platform in individuals with both PTSD and MCI compared to either disorder alone and with unaffected controls. Participants were World Trade Center (WTC) responders recruited through the Stony Brook WTC Health Program. PTSD and MCI were measured with the PTSD Checklist (PCL) and the Montreal Cognitive Assessment, respectively. Compared with unaffected controls, we identified 16 proteins associated with comorbid PTSD–MCI at P < 0.05 (six at FDR < 0.1), 20 proteins associated with PTSD only (two at FDR < 0.1), and 24 proteins associated with MCI only (one at FDR < 0.1), for a total of 50 proteins. The multiprotein composite score achieved AUCs of 0.84, 0.77, and 0.83 for PTSD–MCI, PTSD only, and MCI only versus unaffected controls, respectively. To our knowledge, the current study is the largest to profile a large set of proteins involved in neurobiological processes. The significant associations across the three case-group analyses suggest that shared biological mechanisms may be involved in the two disorders. If findings from the multiprotein composite score are replicated in independent samples, it has the potential to add a new tool to help classify both PTSD and MCI.