Analysis of Post-traumatic Stress Disorder Gene Expression Profiles in a Prospective, Community-based Cohort

Post-traumatic stress disorder (PTSD) is a common and debilitating psychiatric disorder that may occur in individuals exposed to traumatic events such as accidents, interpersonal violence, war, combat, or natural disasters. Additionally, PTSD has been implicated in the development of a variety of chronic conditions including cardiovascular and metabolic diseases, suggesting that the biological alterations of the disorder can manifest themselves as chronic diseases in those suffering from PTSD. The biological underpinnings of the disorder are not well understood. Gene expression studies can illuminate the complex physiology of PTSD reflecting the embodiment of trauma, i.e. the process in which traumatic experiences in our social environments are manifested in our body by genomic mechanisms. To date, gene expression studies that examine the whole transcriptome are scarce and limited to single-timepoint assessments. Here we applied a transcriptome-wide gene expression screen with RNA-sequencing to whole blood samples to elucidate the gene expression signatures associated with the development of PTSD. The study participants (N=72, of whom 21 eventually developed PTSD) are a trauma exposed subsample of participants enrolled in a longitudinal and prospective cohort study of adults living in Detroit, Michigan. PTSD was assessed in a structured telephone interview and whole blood samples were taken both before and after trauma exposure. We found 45 differentially expressed genes associated with PTSD development with an estimated log2 fold change > 1.5 at a nominal p value (p<0.05), however, none of these survived correction for multiple hypothesis testing. Six of the 37 upregulated genes including PAX6, TSPAN7, PXDN, VWC2, SULF1 and NFATC4 were also ubiquitously expressed in all brain regions examined. Subsequent gene set enrichment analysis identified several pathways relating to brain and immune functioning to be enriched in individuals developing PTSD. Longitudinal sampling provides a promising mean to elucidate the pathophysiology underlying the embodiment of trauma.