Pathophysiological pathways of post-traumatic stress disorder in relation to traumatic brain injury: An observational cross-sectional study.

Objective: To investigate changes in serum neuroinflammatory biomarker concentrations and associated psychopathological manifestations in individuals with post-traumatic stress disorder, taking into account the presence or absence of traumatic brain injury. Methods: The study involved 159 male combat veterans who had been involved in combat within the year prior to their inclusion in the study, divided into four groups: veterans without post-traumatic stress disorder or traumatic brain injury (n = 43), veterans without post-traumatic stress disorder but with traumatic brain injury (n = 41), veterans with post-traumatic stress disorder but without traumatic brain injury (n = 38), and veterans with both post-traumatic stress disorder and traumatic brain injury (n = 37). Psychometric parameters (subjective stress severity, depression, avoidance, hyperarousal, intrusive thoughts, and alterations in personality traits) were evaluated. Serum concentrations of antibodies to glial fibrillary acidic protein and neuron-specific enolase were assessed using enzyme-linked immunosorbent assay, while YKL-40, migration inhibitory factor, receptor for advanced glycation end-products, interleukin-34, B-lymphocyte chemoattractant, and triggering receptor expressed on myeloid cells 2 were measured using multiplex assays. Results: Traumatic brain injury presence was associated with reduced severity of depression and avoidance symptoms compared to individuals with post-traumatic stress disorder alone. Elevated serum levels of glial fibrillary acidic protein and neuron-specific enolase antibodies were observed in post-traumatic stress disorder patients, with neuron-specific enolase antibodies particularly increased in the post-traumatic stress disorder + traumatic brain injury group. Notably, YKL-40 levels were decreased in the post-traumatic stress disorder + traumatic brain injury group. Migration inhibitory factor concentration was reduced in post-traumatic stress disorder, while isolated post-traumatic stress disorder was linked to higher receptor for advanced glycation end-products levels. Significant correlations were found between biomarker concentrations and psychometric indices. Conclusion: The findings reveal distinct clinical and biochemical profiles for isolated post-traumatic stress disorder and post-traumatic stress disorder comorbid with traumatic brain injury, reflecting differences in underlying pathophysiological processes. The data suggest involvement of neuroinflammation, blood-brain barrier disruption, and autoimmune mechanisms in post-traumatic stress disorder pathogenesis-particularly when traumatic brain injury is also present. Identified biomarkers may enhance diagnostic and prognostic tools in combat psychiatry.