Mediating role of depression in the relationship between allostatic load and mortality

Allostatic load (AL), an indicator of chronic stress that reflects the cumulative cost of repeated environmental stressors on neural and neuroendocrine responses, has been considered as a potential factor in the development of depression and may increase mortality risk. This study aimed to investigate the association between AL, depression, and mortality in the general population and to evaluate the mediating role of depression in the relationship between AL and mortality. Cross-sectional data from 15,571 participants of the US National Health and Nutrition Examination Survey (NHANES) 2009-2016 were analyzed. AL was calculated by summing numerical values for each biomarker based on predefined risk zones, yielding a score from 0 to 11. Depressive symptoms were assessed by the Patient Health Questionnaire-9 (PHQ-9). The results showed a significant association between AL and mortality (HR = 1.16, 95 % CI: 1.09, 1.23, p < 0.001), with larger effects observed in women and participants aged 40-49. Mediation analysis revealed that depression significantly mediated the relationship between AL and mortality (β = 0.0158, p < 0.001), the indirect effect accounting for approximately 10.45 % of the total effect. Overall, our findings underscore the significant link between AL and mortality, with depression playing a notable mediating role. Future research should focus on exploring the vulnerability of elderly females and middle-aged individuals to chronic stress, using larger, more diverse cohorts and longer follow-up periods to better elucidate mechanisms underlying their increased mortality risk.