Ptsd With Concurrent Excessive Daytime Sleepiness Alters Gene Expression In Military Personnel And Veterans; An Rna-Sequencing Study

Abstract Introduction Up to 91% of military personnel and veterans with posttraumatic stress disorder (PTSD) report co-occurring sleep disturbances, including. insomnia and excessive daytime sleepiness (EDS). Sleep disturbances have been shown not only to increase the risk of developing PTSD, but to exacerbate and maintain PTSD symptomology. The aim of this study was to examine gene expression in active duty military personnel and veterans with PTSD, with and without EDS. Participants were categorized into three groups; 1) PTSD with EDS (PTSDwEDS; n=21), 2) PTSD without EDS (PTSDnoEDS; n=25), or 3) Controls (no PTSD and no EDS; n=57). Methods Participants were 79% male, mean age of 37.6years (SD=11.2years). PTSD symptoms were measured using the PTSD checklist for civilians (PCL-C); participants were classified as PTSD-present using DSM-IV-TR criteria of “moderate-to-severe”. Daytime sleepiness was assessed using the Epworth Sleepiness Scale (ESS), high sleepiness was indicated by an ESS score >13. We performed RNA-seq with Illumina’s HiSeq 2500 in paired-end. We conducted quality control using FastQC and aligned to GRCh38 reference genome using STAR (v2.5.3a). Differentially expressed genes identified using DESeq2 (v1.20.0) with False Discovery Rate of 0.10. Finally, Ingenuity Pathway Analysis (IPA) was conducted to identify dysregulated gene networks. Results Between the Controls and PTSDnoEDS groups, two genes were significantly dysregulated. In controls and PTSDwEDS groups, 251 genes were dysregulated. The IPA networks showed that genes associated with inflammation were significantly dysregulated. Finally, between PTSDwEDS and PTSDnoEDS there were 1,873 significantly dysregulated genes. The IPA networks identified dysregulation of genes related to sleep, fatigue, circadian, and mitochondrial function. Conclusion Taken together this data indicates that EDS that is co-morbidly experienced with PTSD is associated with significant gene dysregulation, above and beyond that observed in participants with PTSD without significant EDS and controls. Treating EDS in military personnel and veterans with PTSD is important. Support This work was supported by the Center for Neuroscience and Regenerative Medicine (CNRM)