The Contribution of Noncommunicable and Infectious Diseases to the Effect of Depression on Mortality: A Longitudinal Causal Mediation Analysis.

Background The increased prevalence of physical diseases among individuals with mental illness contributes to their increased risk of mortality. However, the mediating role of specific diseases in the effect of mental illness on mortality is not well understood.Method We conducted a longitudinal causal mediation analysis using data from beneficiaries of a South African medical insurance scheme from 2011 to 2020. We estimated the overall effect of major depressive disorder (MDD) on mortality and evaluated reductions in this overall effect through hypothetical interventions on the risks of mediating physical diseases using an interventional effects approach. Monte Carlo simulation-based g-computation was used for estimation.Results Among 981,540 individuals, 143,314 (14.6%) were diagnosed with MDD. Mortality risk after 8 years was 6.5% under MDD, and 5.3% under no MDD (risk ratio 1.23, 95% CI = 1.19, 1.26). Overall, 43.4% of this disparity could be attributed to higher rates of physical comorbidities due to MDD. Cardiovascular diseases accounted for 17.8%, followed by chronic respiratory diseases (8.6%), cancers (7.5%), diabetes and chronic kidney disease (5.8%), tuberculosis (4.3%), and HIV (2.7%).Conclusion Within the privately insured population of South Africa, MDD is associated with increased mortality. We found that noncommunicable diseases, rather than infectious diseases, are important mediators of the effect of MDD on mortality.