Immunometabolic alterations in post-traumatic stress disorder

Post-traumatic stress disorder (PTSD) has been linked to various alterations within the immune system, yet the metabolic programming of immune cells remains unexplored. In the current exploratory cross-sectional study, we interrogated immunometabolic function by applying cell-specific metabolic flow cytometry, serum biomarker profiling, and targeted gene expression analysis in peripheral blood mononuclear cells from patients with PTSD (n = 34) compared with healthy controls (n = 32). PTSD was associated with elevated serum IL-6 (p = 0.005) and higher glycolysis- and oxidative pentose phosphate pathway-related markers (identified by CITRUS/SAM using a prespecified FDR threshold of 1%): lactate dehydrogenase (LDH) and glucose-6-phosphate dehydrogenase (G6PD) across adaptive and innate immune cell subsets (CD4⁺ T, CD8⁺ T, B cells, NK cells, monocytes; Cohen's d = 0.51-0.74). CD4⁺ T cells additionally showed elevated glucose transporter 1 (GLUT1, Cohen's d = 0.76), CD8⁺ T cells demonstrated enhanced carnitine palmitoyl transferase 1A (CPT1a, Cohen's d = 0.54) expression, and monocytes exhibited increased acetyl-CoA carboxylase (ACAC, Cohen's d = 0.69). Expression of inflammatory- and stress-related genes was largely comparable between groups. Together, these data provide preliminary evidence for immunometabolic alterations in PTSD at both cellular and systemic levels. These results could contribute to understanding potential pathophysiological mechanisms and support further investigation of immunometabolism in PTSD.