Mortality and the risk of cause-specific death in patients with depression : A nationwide cohort study

Depression is associated with premature mortality, yet the magnitude and heterogeneity of cause-specific mortality risks remain incompletely understood at the population level. We conducted a nationwide cohort study using data from the National Health Insurance Sharing Service linked to mortality records from Statistics Korea. A total of 4,611,122 adults aged ≥ 20 years were followed for a mean of 10.2 years. Depression was identified based on clinical diagnoses. Adjusted hazard ratios (aHRs) for all-cause and cause-specific mortality were estimated using Cox proportional hazards models. During follow-up, 231,440 deaths occurred. Individuals with depression exhibited a higher incidence of all-cause mortality compared with those without depression. After adjustment for demographic, clinical, and lifestyle factors, depression was associated with increased all-cause mortality (aHR, 1.09; 95% CI, 1.07–1.11). Cause-specific analyses revealed the greatest risk elevation for suicide (aHR, 2.05; 95% CI, 1.92–2.19). In contrast, depression was associated with a lower risk of cancer-related mortality (aHR, 0.88; 95% CI, 0.86–0.91). In conclusion, depression was associated with heterogeneous patterns of mortality, characterized by markedly elevated suicide risk and a reduced risk of cancer-related death. These findings suggest distinct underlying biological and behavioral pathways linking depression to specific causes of mortality and highlight the need for cause-targeted prevention and intervention strategies.