Int J Neuropsychopharmacol. 2026 Jun 22:pyag032. doi: 10.1093/ijnp/pyag032. Online ahead of print.
ABSTRACT
BACKGROUND: This study was to explore how serum ghrelin levels modulate the relationship between interleukin-6 (IL-6) and outcomes of antidepressant treatment, specifically focusing on 12-week remission and 24-month relapse in patients with depressive disorders.
METHODS: This investigation involved the analysis of baseline serum levels of ghrelin and IL-6 among 1086 patients enrolled in a naturalistic study of stepwise antidepressant therapy. Remission was determined by a Hamilton Depression Rating Scale (HAMD) score of 7 or less at 12 weeks. Those who responded (HAMD score ≤ 14) at this juncture were subsequently monitored for relapse (HAMD score > 14) quarterly over a 24-month period. The study employed logistic regression models, adjusted for various sociodemographic and clinical factors, to evaluate the interaction between these biomarkers and treatment outcomes.
RESULTS: Findings revealed that while serum ghrelin levels did not independently affect treatment outcomes, they significantly influenced the association between elevated IL-6 levels and the risks of non-remission at 12 weeks and relapse at 24 months. Specifically, high IL-6 levels correlated with poorer outcomes predominantly in the presence of lower ghrelin levels, with these interactions reaching statistical significance in relapse outcomes post-adjustment.
CONCLUSION: The study highlights the complex interplay between IL-6 and ghrelin in shaping the efficacy of antidepressant treatments, demonstrating divergent influences on remission and relapse. These results emphasize the importance of incorporating multiple biomarkers into predictive models to tailor antidepressant strategies more effectively. Continued research is needed to dissect the underlying dynamics of these biomarker interactions.
PMID:42324769 | DOI:10.1093/ijnp/pyag032
