Circulating adipokines and major depressive disorder: a two-sample Mendelian randomization study

Background Observational research has revealed correlations between adipokines and major depressive disorder (MDD). However, the causality of this association remain unknown. Method Two-sample Mendelian randomization (TSMR) was performed to assess the causal effect between adipokines and major depression risk. The analyses were conducted using methods such as inverse variance-weighted-fixed effects (IVW-FE), MR‒Egger, weighted median, weighted mode, and simple mode, which were calculated from the summarized results of a comprehensive genome-wide association study (GWAS). Subsequently, sensitivity analyses were performed to evaluate the robustness of the outcomes. Results Genetically predicted circulating leptin levels showed a positive relationship with MDD risk (OR _IVW =1.12; 95% CI 1.04–1.22; P = 0.005). No causal effect of PAI-1 or resistin on MDD risk was observed. The robustness of this research was ensured by the results derived from the sensitivity analysis. Conclusion These data provide the first evidence of a potential causal relationship between adipokines and MDD. These results indicate that monitoring leptin levels is an effective prevention and control strategy for MDD.