Synergistic effects of lifestyle behaviors on depression progression in middle-aged and older adults: A 23-country longitudinal cohort study with gender-stratified analysis.

OBJECTIVES: This study quantifies the interactive effects of health behaviors-smoking, alcohol consumption, physical activity, and social participation-on depression progression in middle-aged and older adults, with a focus on the moderating role of physical activity and gender differences. METHODS: Using seven years of data from four cohorts (SHARE, HRS, ELSA, and CHARLS), covering 186,066 middle-aged and older adults across 23 countries. A four-dimensional health behavior matrix was constructed: smoking status, alcohol consumption patterns, engagement in moderate-to-vigorous physical activity (MVPA), and social activity, resulting in 16 behavior combinations. Multi-level mixed-effects models assessed longitudinal associations between behavior combinations and standardized depression scores, with gender stratification to explore heterogeneity. RESULTS: Among those engaging in weekly MVPA, depression scores were similar across behavior combinations. In contrast, for those less than weekly MVPA, the combination of smoking, excessive drinking, and socially inactive was associated with a 0.281 SD increase in depression score (95% CI: 0.155-0.407) compared to the reference lifestyle. Gender analysis revealed that women experienced the largest increase in depression scores with a maximum increase of 0.313 SD (95% CI: 0.126-0.500), compared to men (0.288 SD, 95% CI: 0.205-0.370). Additionally, social activity provided a protective effect in the absence of MVPA. CONCLUSIONS: This study demonstrates the core role of physical activity in preventing depression in middle-aged and older adults. Sufficient physical activity mitigates the negative effects of smoking and alcohol, while insufficient activity requires supplementation with socially active. Public health strategies should prioritize physical activity and incorporate gender-specific interventions.