F3. BIOPSYCHOSOCIAL AND EPIGENETIC MARKERS OF HEAT‑STRESS AND POSTTRAUMATIC OUTCOMES IN EMERGENCY RESPONDERS

Background Emergency responders are repeatedly exposed to acute operational stressors and potentially traumatic events, resulting in substantial inter‑individual variability in posttraumatic trajectories. These outcomes span heightened vulnerability to psychopathology through to sustained psychological adaptation. Within psychiatric genomics, such heterogeneity is increasingly understood as arising from dynamic interactions between psychosocial determinants and molecular mechanisms, including environmentally responsive epigenetic modifications such as DNA methylation. Heat‑Stress represents a significant physiological challenge in frontline occupations and may act synergistically with trauma exposure to influence long‑term biological regulation, stress‑response pathways, and mental health outcomes. Aim To characterise (1) cross‑sectional and longitudinal differences in DNA‑methylation–based biological aging across emergency service professions, and (2) Heat‑Stress–related biological pathways enriched in genome‑wide CpG-gene associations. These analyses form part of a broader investigation into biopsychosocial and molecular contributors to posttraumatic mental health in emergency responders. Methods Psychosocial survey data and saliva‑derived biological samples were collected from 652 emergency responders. DNA methylation was measured using Illumina EPICv2 arrays. All statistical analyses were performed using standard pipelines in R. Epigenetic age was estimated using standard methods. Different epigenetic age accelerations were calculated depicting different biological mechanisms - Pheno Age, Hannun Age, Horvath Age and Grim Age. Linear and mixed‑effects models assessed associations between profession, timepoint, and age‑acceleration metrics, adjusting for demographic, trauma‑related, and cellular covariates. Heat stress associated CpG-gene links (p < 0.05) were extracted from combined‑profession and profession‑specific genome‑wide models. GOstats hypergeometric testing (p < 0.001) identified enriched Gene Ontology Biological Process pathways. Results Cross‑sectionally, only Pheno age acceleration demonstrated a marginal profession effect (p = 0.047). Longitudinal analyses revealed significant Timepoint × Profession interactions for Hannum Age acceleration (p = 1.66 × 10⁻⁵), indicating occupation‑specific divergence in epigenetic aging trajectories, particularly among firefighters. GO enrichment identified four significant pathways - morphogenesis, epithelial cell development, actin filament‑based processes, and structural formation, suggesting cytoskeletal and tissue‑remodelling mechanisms underpin the observed heat‑stress responses. Discussion Emergency responders exhibit shared Heat stress related biological pathways but differ in longitudinal epigenetic aging patterns. These findings highlight potential mechanistic links between occupational stress exposure, cellular structural regulation, and long‑term mental health trajectories. Integrating psychosocial phenotypes with genomic and epigenetic markers may advance precision approaches for predicting and supporting responder wellbeing.