The association between metabolically healthy obesity and risk of depression: a systematic review and meta-analysis

This review aimed to explore the association between metabolically healthy obesity (MHO) and the risk of depression. Databases (EMBASE, PubMed, Web of Science, Cochrane Library) were searched up to 20 June 2024. Observational studies were included if they compared groups with MHO, metabolically unhealthy nonobesity, and metabolically unhealthy obesity to groups with metabolically healthy nonobesity for the risk of depression. The random-effect model was used to calculate the pooled odds ratios (ORs). Subgroup analyses and meta-regressions were conducted according to age, study design, definition of MHO, BMI cut-off value, depression assessment method, geographic location, ethnicity, development status, and gender to explore the sources of heterogeneity. Three cohorts and 9 cross-sectional studies (N = 1,277,267 participants) were included in this review. Individuals with MHO (OR 1.08 [95% CI 1.04, 1.12], I² = 88.3%), metabolically unhealthy nonobesity (OR 1.15 [95% CI 1.04, 1.28], I² = 99.6%), and metabolically unhealthy obesity (OR 1.30 [95% CI 1.12, 1.51], I² = 99.8%) had an increased risk of depression than individuals with metabolically healthy nonobesity. The association between MHO and risk of depression was stronger in women (OR = 1.14; 95% CI: 1.08-1.20) and populations from North America (OR = 1.26; 95% CI: 1.01-1.58) and Europe (OR = 1.23; 95% CI: 1.07-1.41). Inconsistencies in MHO definitions and BMI cutoff values across studies were important sources of heterogeneity (subgroup analysis: P_Q = 29.87, p = 0.001; meta-regression: p = 0.015, R² = 100%). MHO was associated with an increased risk of depression, particularly among women and populations from North America and Europe. These high-risk groups need personalized interventions. Standardizing definition for MHO could enhance comparability across studies. Future prospective cohort studies are needed to validate our findings by including populations from developing nations and employing rigorous definitions.