Interaction between ghrelin and social support predicts antidepressant treatment outcomes in patients with depression

We aimed to investigate the interactive effects of baseline perceived social support and serum ghrelin levels on antidepressant treatment outcomes, specifically 12-week remission and 24-month relapse, in patients with depressive disorders. This prospective naturalistic study included a large cohort of patients treated for depression under routine clinical conditions. Social support was measured using the Multidimensional Scale of Perceived Social Support, and serum ghrelin was quantified at baseline. Participants received individualized pharmacological treatments over 12 weeks (N = 1086), followed by a 24-month follow-up for relapse (N = 710). Logistic regression and interaction analyses evaluated associations between social support, ghrelin, and treatment outcomes, controlling for relevant covariates. Neither social support nor serum ghrelin independently predicted 12-week remission or 24-month relapse. However, a significant interaction emerged: lower ghrelin levels were associated with poorer outcomes exclusively in patients with low social support. These interactions were significant after adjusting for clinical and demographic covariates and were observed despite no direct correlation between ghrelin and social support. Our findings highlight the importance of considering biopsychosocial interactions in predicting antidepressant treatment outcomes. Clinically, simultaneous assessment of social support and ghrelin may enhance risk stratification and guide personalized interventions. Future research should investigate underlying mechanisms and explore interventions aimed at boosting social support to mitigate biological vulnerabilities.