Investigating the visceral adiposity–major depressive disorder link: a cross-sectional NHANES 2011–2014 analysis and Mendelian randomization study

Abstract Background In recent years, the intricate interplay between physical health and mental well-being has garnered significant attention, specifically highlighting the potential influence of adipose tissue distribution, notably visceral adipose tissue (VAT) in the abdomen, on psychological states. VAT is implicated in systemic inflammation and metabolic disruptions, which are hypothesized to contribute to the onset and progression of mental health disorders, particularly major depressive disorder (MDD). Methods To investigate the relationship between VAT and MDD, we analyzed data from the National Health and Nutrition Examination Survey (NHANES) covering 2011 to 2014. We employed multivariate logistic regression analysis to ensure the robustness of our findings. Interaction and stratified analyses were conducted to elucidate the complex relationships between these variables, and restricted cubic spline (RCS) plots were utilized to visualize these interactions. Furthermore, Mendelian randomization (MR) analysis was performed to ascertain the directionality of the causal relationship. Results The weighted, multivariable-adjusted logistic regression analysis demonstrated a positive correlation between VAT and the risk of MDD, with an odds ratio (OR) of 1.635 (95% CI 1.004–2.664). Further analysis, after accounting for potential confounding factors, revealed a more pronounced association in women, with an OR of 1.903 (95% CI 1.051–3.445). Interaction analysis indicated a potential gender-specific association between VAT and MDD, suggesting that the relationship may differ by sex (P for interaction = 0.003). Mendelian randomization (MR) analysis supported a bidirectional causal relationship between VAT and MDD. Sensitivity analyses confirmed the robustness and reliability of the results. Conclusion This study suggests that monitoring and managing VAT could enhance our understanding of the pathogenesis of MDD and provide new insights for developing more effective treatment strategies.