Background: Obesity (OB) and major depressive disorder (MDD) are chronic conditions associated with disease burden, and their comorbidity appears more common among women. Mechanisms linking these conditions may involve inflammatory and metabolic pathways. The goal of this study was to evaluate the impact of MDD on relationships between OB and cardiometabolic function, and sex differences therein. Materials and Methods: Adult offspring from the New England Family Studies (NEFS) were assessed at ages 39-50, including anthropometry, cardiometabolic profile assays, and metabolic syndrome. Individuals were grouped by body mass index (BMI) and MDD status: healthy weight with (n = 50) or without MDD (n = 95) and obese with (n = 79) or without MDD (n = 131). The interaction of (recurrent) MDD and BMI on cardiometabolic markers was tested using quantile regression models. Results: Participants with MDD exhibited significantly higher hemoglobin A1c (HbA1c) than those without MDD (5.60% vs. 5.35%, p < 0.05). Women with comorbid recurrent MDD and OB had higher HbA1c levels compared to obese women without MDD (5.75% vs. 5.44%, p < 0.05); an interaction between MDD and BMI status was not observed among men. Conclusions: We demonstrated sex differences in the interaction between BMI and recurrent MDD status on a primary biomarker for diabetes risk, suggesting a common metabolic pathway predisposing women to these comorbid conditions. Further investigation is needed to identify mechanisms that may lead to more effective, sex-dependent screening and therapies.
Keywords: diabetes; epidemiology; long-term weight; mental health; obesity.