The Interplay Between Insulin Resistance, Inflammation, and Depression Risk: A Population-Based Study

Background: Depression is a common mental disorder with a complex etiology involving metabolic and inflammatory pathways. Insulin resistance (IR) has been implicated in the development of depression, but the underlying mechanisms remain unclear. The albumin-to-globulin ratio (AGR) is a marker of systemic inflammation and nutritional status. This study investigates the potential mediating role of AGR in the association between IR and depression. Methods: Data were obtained from the National Health and Nutrition Examination Survey (NHANES). Depression was assessed using the Patient Health Questionnaire-9 (PHQ-9), with a score ≥ 10 indicating clinically relevant depressive symptoms. IR was evaluated using the Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), and AGR was calculated from serum albumin and globulin levels. Both HOMA-IR and AGR were categorized into quartiles. Multivariate logistic regression models were used to examine the associations, and mediation analysis was conducted to quantify the indirect effect of AGR. Results: Higher HOMA-IR was significantly associated with an increased risk of depression, whereas AGR showed a negative correlation with depression risk. Mediation analysis demonstrated that AGR partially mediated the association between HOMA-IR and depression, accounting for 0.327% of the total effect. Conclusion: These findings suggest that metabolic dysfunction and systemic inflammation play a role in the pathophysiology of depression. AGR may serve as a potential biomarker linking IR to depression risk. Future studies are needed to explore the underlying biological mechanisms and potential therapeutic implications.