Abstract
<title>Abstract</title> <p> Backgroud Functional dyspepsia (FD) is a common disorder of gut-brain interaction. Patients respond often poorly to proton pump inhibitors and prokinetics. Although antidepressants may be beneficial, their efficacy is inconsistent. This study aimed to investigate the potential associations of serum 5-hydroxytryptamine (5-HT) and tryptophan/5-HT (Trp/5-HT) levels for the efficacy of combined antidepressant therapy in patients with FD, and to analyze its associations with clinical symptoms, psychological status, and quality of life. Methods A total of 42 patients diagnosed with FD according to the inclusion criteria were enrolled.All patients received a 4-week regimen of proton pump inhibitors and/or prokinetics combined with an antidepressant. Serum levels of 5-HT, gamma-aminobutyric acid (GABA), acetylcholine (Ach), dopamine (DA), L-tryptophan (L-Try), and vanillylmandelic acid (VMA) were measured using ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The Trp/5-HT reflecting 5-HT conversion efficiency was calculated. Clinical symptoms and psychological status were assessed using the Dyspepsia symptom severity (DSS), 10-item short form of Nepean dyspepsia index (SF-NDI), Generalized anxiety disorder-7 (GAD-7), Patient health questionnaire-9 (PHQ-9), Somatic symptom scale-8 (SSS-8), and Perceived stress scale-4 (PSS-4). Patients were categorized into a responder group (symptom improvement rate ≥ 50%) and a non-responder group. Binary logistic regression analysis was performed to identify predictors of treatment response.Quartile-based trend analysis using the Cochran-Armitage test was performed to evaluate dose-response relationships. Results Serum 5-HT levels were significantly lower in the responder group than in the non-responder group ( <italic>p</italic> = 0.021). Logistic regression analysis identified serum 5-HT as an independent predictor of treatment response ( <italic>OR</italic> = 0.990,95% <italic>CI</italic> :0.981–0.999, <italic>p</italic> = 0.034). The Trp/5-HT was positively correlated with SF-NDI ( <italic>r</italic> = 0.344, <italic>p</italic> = 0.026) and PSS-4 ( <italic>r</italic> = 0.309, <italic>p</italic> = 0.046), but not with DSS, GAD-7, SSS-8, or PHQ-9. Moreover, the responder group exhibited a lower Trp/5-HT potential trend compared with the non-responder group, and quartile analysis demonstrated a directionally consistent but non-significant trend ( <italic>p</italic> = 0.111). Conclusion Lower serum 5-HT levels appear to be associated with a more favorable outcome in combination antidepressant therapy in FD. The lower Trp/5-HT may have a potential trend for treatment response. These results provide a possible explanation for the variable efficacy of antidepressants. Further large prospective studies are needed to confirm these findings. </p>