Neurobiological correlates of PTSD chronicity: Integrating stress biomarkers and brain morphometric changes.

OBJECTIVE: Aim: This study aimed to investigate how the chronicity of post-traumatic stress disorder (PTSD) shapes neurobiological functioning by integrating biochemical stress-related biomarkers (serotonin, cortisol, noradrenaline, IL-12, IGF-1, CASP-9, nNOS, IL-10) with morphometric and microstructural brain parameters assessed using magnetic resonance imaging (MRI). A further objective was to determine whether early PTSD (≤5 years) and long-term PTSD (>5 years) exhibit distinct profiles of neuroinflammatory, neurodegenerative, and neuroplastic alterations, with particular focus on brain regions involved in emotion regulation, memory, and cognitive control (hippocampus, amygdala, insular cortex, and prefrontal cortex).

PATIENTS AND METHODS: Materials and Methods: The study included 92 adult male miners and mine rescue workers exposed to life-threatening events. Participants were assigned to three groups: PTSD ≤5 years (n = 33), PTSD >5 years (n = 31), and controls without PTSD symptoms (n = 28). PTSD diagnosis was confirmed using the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5). MRI was performed on a 1.5 T General Electric (GE) Optima 360 scanner and included volumetric T1-weighted imaging, T2-weighted FLAIR, SWAN, and diffusion tensor imaging. Assessed brain parameters included ventricular width, amygdala dimension, corpus callosum thickness, insular cortex thickness, and lateral fissure width. Biochemical markers were quantified using standard laboratory assays.

RESULTS: Results: Significant differences across all groups were observed for nearly all biomarkers and structural brain measures (p < 0.001). Early PTSD was characterized by elevated neuroinflammatory markers, reduced anti-inflammatory and neurotrophic activity (lower IL-10 and IGF-1), early ventricular enlargement, thinning of the corpus callosum and insular cortex, and reduced amygdala dimensions. Long-term PTSD demonstrated pronounced cortical atrophy, including marked widening of the lateral fissures, significant third-ventricle enlargement, and persistent thinning of the insular cortex and callosal body. Cortisol showed the strongest positive correlation with structural degeneration. Noradrenaline exhibited a potential compensatory effect, demonstrating negative correlations with ventricular width. The control group displayed physiological, homeostatic correlation patterns.

CONCLUSION: Conclusions: The chronicity of PTSD substantially modulates both biochemical and structural brain profiles. Early PTSD reflects acute neuroinflammation and impaired neuroprotection, whereas long-term PTSD is dominated by progressive neurodegeneration associated with chronic dysregulation of the hypothalamic- pituitary-adrenal (HPA) axis. Integrating biomarker profiles with MRI-derived measures provides a robust framework for identifying markers of disease progression and for developing phase-specific therapeutic strategies aimed at mitigating atrophy, modulating stress-response systems, and supporting neuroplasticity.