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-exposures or natural disasters. PTSD is a significant public health issue with a high disease burden associated with substantial health care costs and several comorbidities negatively affecting an individual’s quality of life. The biological underpinnings of the disorder are not well understood. Gene expression studies can shed light into the complex physiology of PTSD. However, to date, studies employing a hypothesis-free approach examining the whole transcriptome are scarce and are limited to assessment of only one timepoint. Here we applied a transcriptome-wide gene expression screen with RNA-sequencing to whole blood samples in order to eludidate the gene expression signatures associated with the development of PTSD. The study participants (n=72, of which 21 eventually developed PTSD) are a subsample of participants enrolled in a longitudinal and prospective cohort study of adults living in Detroit, Michigan called Detroit Neighborhood Health Study. PTSD was accessed in a structured telephone interview and whole blood samples were taken both before and after trauma exposure. A linear mixed model was used in order to analyze the gene expression data optimized for repeated measures. We found 45 differentially expressed genes in our cohort of individuals who developed PTSD with an estimated log2 fold change \u3e 1.5 at a nominal p value (p\u3c0.05). Seven of our upregulated genes including PAX6, TSPAN7, PXDN, VWC2, SULF1, PAX3 and NFATC4 were also expressed in the brain, while four of our down regulated genes including UGT2A3, ACTP1, HSPB7 and FMOD were also found to be expressed in the brain. Gene set enrichment analysis of the differentially expressed genes implicated several pathways relating to brain functions and immune functioning to be enriched in individuals developing PTSD. No differentially expressed genes were observed after multiple test correction. However, the longitudinal sampling of participants prior to the development of PTSD provides a promising mean to gain insight into the pathophysiology underlying PTSD development in future studies