Abstract
While the immunological dysfunction in combat Veterans with post-traumatic stress disorder (PTSD) has been well documented, the precise mechanisms remain unclear. The current study evaluated the role of microRNA (miR) in immunological dysfunction associated with PTSD. The presence of peripheral blood mononuclear cells (PBMC) and various lymphocyte subsets in blood collected from PTSD patients were analyzed. Our studies demonstrated that the numbers of both PBMC and various lymphocyte subsets increased significantly in PTSD patients. When T cells were further analyzed, the percentage of Th1 cells and Th17 cells increased, regulatory T cells(Tregs) decreased, while Th2 cells remained unaltered in PTSD patients. These data correlated with increased plasma levels of IFN-γ and IL-17 while IL-4 showed no significant change. The increase in PBMC counts, Th1 and Th17 cells seen in PTSD patients correlated with the clinical scores. High-throughput analysis of PBMCs for 1163 miRs showed that the expression of a significant number of miRs was altered in PTSD patients. Pathway analysis of dysregulated miRs seen in PTSD patients revealed relationship between selected miRNAs and genes that showed direct/indirect role in immunological signaling pathways consistent with the immunological changes seen in these patients. Of interest was the down-regulation of miR-125a in PTSD, which specifically targeted IFN-γ production. Together, the current study demonstrates for the first time that PTSD was associated with significant alterations in miRNAs, which may promote pro-inflammatory cytokine profile. Such epigenetic events may provide useful tools to identify potential biomarkers for diagnosis, and facilitate therapy of PTSD.
Highlights
Post-traumatic stress disorder (PTSD) is a psychiatric disorder
Cell population changes in the blood of PTSD patients We first investigated the number of peripheral blood mononuclear cells (PBMC) found in patients with PTSD when compared to the controls
Our analysis demonstrated that PBMC counts showed a significant increase in patients with PTSD when compared to the controls (Figure 1A)
Summary
Post-traumatic stress disorder (PTSD) is a psychiatric disorder. Exposure to life-threatening events such as war, earthquake, sexual assault or family violence usually lead to PTSD [1]. About 30% of Vietnam Veterans developed PTSD [2]. It was detected among 8% of Gulf War Veterans [3] and up to 35% of the military personnel deployed to Iraq and Afghanistan [4]. Patients with PTSD may display interpersonal withdrawal and progressive decrease in muscle mass, increased risk of osteoporosis and fractures, as well as dementia due to tissue damage [5,6,7]. Patients with PTSD are six times more at risk of committing suicide and having marital problems, and the annual loss of productivity is estimated to be approximately $3 billion [8]. There is no cure for patients with PTSD, and available treatments often are not completely effective
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