Individual and joint associations of depression and physical multimorbidity with all-cause mortality: a prospective cohort study

The study aimed to investigate the separate, interactive, and combined effects of depression and physical multimorbidity on all-cause mortality using data from the National Health and Nutrition Examination Survey (NHANES) 2005-2016. Depression was assessed using the Patient Health Questionnaire-9 (PHQ-9), and multimorbidity was defined as the presence of ≥ 2 chronic conditions. Cox proportional hazards models were used to assess these associations. During a median follow-up of 8.3 years (interquartile range, 5.4-11.4), 3,005 deaths occurred. After adjusting for potential confounders and multimorbidity, each one-point increase in depression score was associated with a 3% higher risk of mortality (hazard ratio [HR]: 1.03, 95% confidence interval [CI]: 1.02-1.04). Compared to those without depressive symptoms, mild and moderate to severe symptoms were linked to a 27% (HR: 1.27, 95% CI: 1.11-1.47) and 37% (HR: 1.37, 95% CI: 1.17-1.61) higher mortality risk, respectively. However, among women, only moderate to severe depression was significantly associated with increased mortality (HR: 1.50, 95% CI: 1.19-1.89). After adjusting for potential confounders and depression, multimorbidity was associated with a 64% higher mortality risk (HR: 1.64, 95% CI: 1.46-1.86). No significant interaction between depression and multimorbidity was found. Joint analysis showed that among participants without multimorbidity, moderate to severe depressive symptoms increased mortality risk (HR: 1.54, 95% CI: 1.09-2.17). In those with multimorbidity, risk increased with depression severity, peaking at HR: 2.22 (95% CI: 1.85-2.65). These findings highlight depression and multimorbidity as independent mortality risk factors, with their combined presence further amplifying this risk.