Association of organ dysfunction status trajectories with incident depression across BMI and clinical obesity

Obesity is associated with depression, but BMI may not fully capture the systemic burden of excess adiposity. We investigated whether obesity-related organ dysfunction trajectories were associated with incident depression under BMI-based and clinical obesity classifications. We analyzed 404,146 UK Biobank participants. BMI-based obesity was defined using ethnicity-specific thresholds, and clinical obesity was defined by excess adiposity plus hospital-recorded organ dysfunction. Organ dysfunction trajectories were assessed over two consecutive 2-year periods after baseline and categorized as persistent no dysfunction, no → dysfunction, dysfunction → no, and persistent dysfunction. Follow-up began 4 years after baseline. Cox models estimated adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs). Across BMI categories, organ dysfunction trajectories were consistently associated with higher depression risk. Persistent dysfunction was associated with higher depression risk in normal-weight, overweight, and obese participants, with aHRs of 1.91 (95% CI, 1.49-2.45), 2.57 (95% CI, 2.24-2.94), and 2.48 (95% CI, 2.19-2.82), respectively. Similar associations were observed using clinical obesity categories. Compared with persistent no dysfunction, persistent dysfunction was associated with higher depression risk in participants with no clinical obesity and preclinical obesity, with aHR of 2.38 (95% CI, 1.86-3.04) and 2.30 (95% CI, 1.93-2.74), respectively. When obesity categories were compared within organ dysfunction trajectories, clinical obesity classification showed stronger overall risk stratification than BMI-based classification, while the joint framework provided the best model performance. BMI-based and clinical obesity classifications may therefore provide complementary information for depression risk stratification.