Excessive daytime sleepiness is associated with altered gene expression in military personnel and veterans with posttraumatic stress disorder: An RNA sequencing study

Study Objectives: Posttraumatic stress disorder (PTSD) is a common condition for military personnel and veterans. PTSD has been shown to impact gene expression, however, to date no study has examined comorbid conditions which may also impact gene expression, for example, excessive daytime sleepiness (EDS). As such, this study sought to examine gene expression using RNA sequencing across three group comparisons of military personnel and veterans: (1) PTSD with EDS (PTSDwEDS) versus PTSD without EDS (PTSDw/outEDS), (2) Controls (no PTSD or EDS) versus PTSDwEDS, and (3) Controls versus PTSDw/outEDS. Methods: We performed experimental RNA-seq using Illumina's HiSeq 2500 Sequencing System. We also used Ingenuity Pathway Analysis (IPA), a bioinformatics application, to identify gene pathways and networks which may be disrupted. Results: There were only two genes that were significantly dysregulated between the Controls and PTSDw/outEDS, therefore IPA analysis was not conducted. However, comparisons revealed that there was significant gene dysregulation between Controls and the PTSDwEDS (251 genes), and the PTSDwEDS versus the PTSDw/outEDS (1,873 genes) groups. Four candidate networks were identified via the IPA software for analysis. Significantly dysregulated genes across the four candidate networks were associated with sleep and circadian function, metabolism, mitochondrial production and function, ubiquitination, and the glutamate system. Conclusions: These results suggest that PTSD with concurrent EDS is associated with gene dysregulation. This dysregulation may present additional biological and health consequences for these military personnel and veterans. Further research, to track these gene changes over time and to determine the cause of the EDS reported, is vital.