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.