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. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study was supported by the National Institutes of Health Grants [R01DA022720, R01DA022720-S1, RC1MH088283, R01 MD011728]. RNA sequencing was supported by the Illinois Health Disparities Institute and performed by the DNA Services Lab at the University of Illinois at Urbana-Champaign. J. Dahrendorff was supported by the COPH Doctoral Fellowship of the University of South Florida. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The Institutional Review Board of the University of Michigan and the University of North Carolina-Chapel Hill gave ethical approval for this work. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors. [https://github.com/dahrendorff/Longitudinal\_RNAseq\_PTSD/blob/main/Longitudinal\_RNAseq\_PTSD.R][1] [1]: https://github.com/dahrendorff/Longitudinal_RNAseq_PTSD/blob/main/Longitudinal_RNAseq_PTSD.R