Intensity and exposure proximity as determinants of differential stress-related health outcomes

Civilian populations under continuous traumatic stress (CTS) face long-term health consequences mediated primarily by glucocorticoid stress pathways. To assess the health impact of exposure to CTS and subsequent acute trauma, we conducted a retrospective observational study of 208,625 adults in southern and central Israel exposed to CTS and aftermath of October 7, 2023 attacks. Using anonymized electronic health records (2005-2024) and a serial cross-sectional design stratified by exposure level, sex, and age, we assessed psychiatric morbidity, medication use, immune disease, mortality, and blood biomarkers. CTS exposure level was defined by residential proximity to the Gaza border as high, moderate, or low (15, 30-60, and 90 seconds to shelter, respectively), and acute trauma effects were assessed by comparing ten months before and after October 7.Prior to October 7, psychiatric morbidity increased across all exposure groups, with moderately exposed women showing the highest baseline prevalence. Following October 7, morbidity rose in an exposure-dependent manner, among highly exposed women, with predominant antidepressant use compared with higher anxiolytic use among moderately exposed women. Highest vulnerability was observed in ages 46-64.Sex-specific interactions were observed, including autoimmune disease and elevated MCV among moderately exposed women, and pneumonia with elevated WBC among highly exposed men. GGT was linked to reduced psychiatric risk in men, whereas elevated alkaline phosphatase was associated with increased autoimmune risk in women. Highly exposed men showed 374% higher mortality than women and 88% higher mortality than moderately exposed men. Age, sex, and biomarker-based screening may mitigate CTS-related disease.