Neurobiological and Existential Profiles in Posttraumatic Stress Disorder: The Role of Serotonin, Cortisol, Noradrenaline, and IL-12 Across Chronicity and Age

Posttraumatic Stress Disorder (PTSD) is characterized by disruptions in central nervous system functioning and existential crises, yet the mechanistic links between neurobiological processes and dimensions of life meaning and identity remain underexplored. The aim of this study was to examine the relationships between stress biomarkers (serotonin, cortisol, noradrenaline, and interleukin-12 [IL-12]) and existential attitudes (measured using the Life Attitude Profile (Revised) [LAP-R]) in mining rescuers, considering PTSD duration and participant age. This cross-sectional study included 92 men aged 18-50 years, divided into three groups: no PTSD (n = 28), PTSD ≤ 5 years (n = 33), and PTSD > 5 years (n = 31). Serum levels of four biomarkers and LAP-R scores across eight domains were evaluated. Statistical analyses employed nonparametric tests, including the Kruskal-Wallis test for overall group differences (with Wilcoxon r effect sizes for pairwise comparisons, Mann-Whitney U tests for post hoc pairwise comparisons, and Spearman's rank correlations for biomarker-LAP-R associations. Age effects were assessed in two strata: 18-35 years and 36-50 years. Kruskal-Wallis tests revealed significant group differences (<i>p</i> < 0.001) for all biomarkers and most LAP-R domains, with very large effect sizes (r > 0.7) in pairwise comparisons for serotonin (control median: 225.2 ng/mL vs. PTSD ≤ 5y: 109.9 ng/mL, r = 0.86; vs. PTSD > 5y: 148.0 ng/mL, r = 0.86), IL-12 (control: ~8.0 pg/mL vs. PTSD ≤ 5y: 62.4 pg/mL, r = 0.86; vs. PTSD > 5y: ~21.0 pg/mL, r = 0.69), and LAP-R scales such as Life Purpose (control: 54.0 vs. PTSD ≤ 5y: 39.0, r = 0.78; vs. PTSD > 5y: 20.0, r = 0.86) and Coherence (control: 53.0 vs. PTSD ≤ 5y: 34.0, r = 0.85; vs. PTSD > 5y: 23.0, r = 0.86). The PTSD ≤ 5y group exhibited decreased serotonin, cortisol (median: 9.8 µg/dL), and noradrenaline (271.7 pg/mL) with elevated IL-12 (all <i>p</i> < 0.001 vs. control), alongside reduced LAP-R scores. The PTSD > 5y group showed elevated cortisol (median: ~50.0 µg/dL, <i>p</i> < 0.001 vs. control, r = 0.86) and normalized IL-12 but persistent LAP-R deficits. Older participants (36-50 years) in the PTSD ≤ 5y group displayed improved existential attitudes (e.g., Life Purpose: 47.0 vs. 27.5 in 18-35 years, <i>p</i> < 0.001), whereas in PTSD > 5y, age exacerbated biological stress (cortisol: 57.6 µg/dL vs. 36.1 µg/dL, <i>p</i> = 0.003). Spearman correlations revealed stage-specific patterns, such as negative associations between cortisol and Death Acceptance in PTSD > 5y (ρ = -0.49, <i>p</i> = 0.005). PTSD alters biomarker levels and their associations with existential dimensions, with duration and age modulating patient profiles. These findings underscore the necessity for integrated therapies addressing both biological and existential facets of PTSD.