The influence of metabolic dysfunction on depressive symptom trajectories: A one-year follow-up study

This study explored the role of metabolic syndrome (MetS) and health-related behaviors in the progression of depressive symptoms over a one-year naturalistic follow-up in patients with depressive disorder. Using data from 153 participants recruited through the Signature Biobank at a psychiatric emergency setting, we tested whether MetS mediated the relationship between health-related behaviors such as smoking, alcohol and drug use, and sleep, and depressive symptom trajectories. Linear mixed models revealed that while depressive symptoms significantly decreased over time, higher MetS score was associated with a slower improvement in depressive symptoms. However, health-related behaviors did not independently predict depressive symptoms, nor did they exert significant indirect effects through MetS. Smoking, alcohol, and drug use, as well as sleep efficiency, showed no direct or mediated association with depression over time. These findings suggest that MetS may represent a biological vulnerability contributing to unfavorable depression trajectories, independent of common behavioral risk factors. The persistent increase in MetS scores over time supports its potential role as a moderator of treatment response, possibly through mechanisms related to inflammation and neuroendocrine dysregulation. Although limitations such as self-reported measures and the acute nature of the clinical population may affect generalizability, this study highlights the importance of addressing metabolic dysfunction in depression management. Future research should further investigate the biological underpinnings linking MetS and depression to inform more personalized and effective therapeutic strategies.