Abstract
Introduction: Post-traumatic stress disorder (PTSD) is increasingly recognized as a systemic neuroimmune disorder. Despite growing evidence of immune dysregulation, the cellular exhaustion and apoptotic mechanisms in military personnel with PTSD remain insufficiently characterized.
Objective: To characterize the immunological and biochemical features of PTSD in military personnel through a comprehensive analysis of cellular immune responses, regulatory T-cells, and markers of cellular exhaustion and apoptosis.
Methods: A cohort study enrolled 40 military personnel with DSM-5-diagnosed PTSD and 42 combat-exposed controls without PTSD. Immunophenotyping of peripheral blood lymphocytes (CD3+, CD4+, CD8+, CD19+, NK cells) was performed by flow cytometry (BD FACSCalibur). Exhaustion markers (PD-1/CD279, PD-L1/CD274, TIM-3/CD366, CD38) and apoptosis markers (FAS/CD95, FasL/CD178) were assessed on cytotoxic CD8+ T-cells and NK cells. Serum IL-6 and biochemical parameters were measured using automated analyzers.
Results: PTSD patients demonstrated a significantly elevated CD4/CD8 ratio (2.59 ± 1.62 vs. 1.15 ± 0.71; p<0.001), reduced NK cells (11.84 ± 5.22% vs. 14.67 ± 7.23%; p=0.046), and elevated B-lymphocytes (24.22 ± 12.2% vs. 13.27 ± 7.24%; p<0.001). Upregulated expression of PD-1 (p=0.020), PD-L1 (p=0.002), and TIM-3 (p=0.008) on CD8+ cells, and TIM-3 (p<0.001), FAS (p=0.026), and FasL (p=0.036) on NK cells, indicated immune exhaustion and apoptotic activation. IL-6 was elevated (7.92 ± 3.34 vs. 6.12 ± 2.26 pg/mL; p=0.005). Biochemical alterations included hyperglycemia, elevated ALT/AST, creatinine, and reduced total protein (all p<0.05).
Conclusions: PTSD in military personnel is associated with an integrated immuno-metabolic phenotype characterized by chronic immune activation, cellular exhaustion, and apoptotic dysregulation. The identified markers—PD-1, PD-L1, TIM-3, FAS/FasL, and IL-6-represent promising candidates for multiparametric PTSD biomarker panels and personalized therapeutic targets.