Exploring the combined influence of serum serotonin and brain-derived neurotrophic factor on depression remission: Short- and long-term responses

Psychiatry Res. 2025 Sep 23;353:116741. doi: 10.1016/j.psychres.2025.116741. Online ahead of print.

ABSTRACT

This study aimed to investigate the independent and interactive combined effects of serum serotonin (s5-HT) and brain-derived neurotrophic factor (sBDNF) levels on antidepressant remission at 12 weeks and 12 months in patients with depressive disorders. Baseline levels of s5-HT and sBDNF were measured in 1086 patients receiving stepwise antidepressant pharmacotherapy. Remission was defined as a Hamilton Depression Rating Scale score ≤7. Logistic and multinomial regression analyses examined individual and interactive biomarker effects, adjusting for relevant covariates. The clinical relevance was assessed using Number Needed to Treat (NNT). Higher baseline s5-HT significantly predicted 12-week remission but showed no association with 12-month remission. Conversely, higher baseline sBDNF was significantly associated with 12-month remission but not with 12-week remission. A significant interaction between s5-HT and sBDNF was observed specifically at 12 months, where patients with low levels of both biomarkers showed markedly reduced remission rates. NNT analyses demonstrated substantial clinical utility in combining biomarkers, with an improved NNT of 6.8 when identifying patients at risk for poor long-term remission. The interactive combination of low baseline s5-HT and sBDNF levels strongly predicts reduced 12-month antidepressant remission, highlighting its potential for guiding personalized clinical management to enhance long-term depression outcomes.

PMID:41014653 | DOI:10.1016/j.psychres.2025.116741