Visceral Adiposity and Risk of Depression Independent of General and Central Adiposity: A Prospective Cohort Study

Introduction: Visceral adipose tissue (VAT) is a metabolically active fat depot linked to cardiometabolic disease, but its relationship with depression independent of general and central adiposity remains unclear. We investigated the association of MRI-quantified VAT with the incidence of depression and evaluated whether it predicts depression risk beyond the body mass index (BMI) and the waist-to-height ratio (WHtR). Methods: We analyzed 50,729 UK Biobank participants who underwent abdominal MRI between 2014 and 2020 and had no history of depression at baseline. Baseline VAT volume, BMI, and WHtR were measured, and the incidence of depression was ascertained via linked hospital, primary care, and mortality records. Cox proportional hazard models estimated hazard ratios (HRs) for depression, and restricted cubic splines assessed potential nonlinear associations. Mediation analyses quantified the extent to which VAT accounted for associations of BMI and WHtR with depression. Results: Over a median follow-up of 15.4 years, each 1-SD higher VAT was associated with a 29% increased risk of depression (HR, 1.29; 95% confidence interval, 1.19–1.39), independent of sociodemographic, behavioral, and clinical factors. Participants in the highest VAT quartile had nearly double the risk compared with the lowest quartile. BMI and WHtR showed nonlinear associations but were not independently associated with depression after adjusting for VAT. VAT provided superior predictive value compared with BMI and WHtR, and mediation analyses indicated that it accounted for most of their observed associations. Conclusions: Visceral adiposity, rather than general (BMI-defined) or central (WHtR-defined) adiposity, is the principal adipose-related predictor of depression risk. These findings highlight VAT as the principal adiposity measure for risk assessment and a potential target for prevention.