Feasibility of Using Serum, Plasma, and Platelet 5-hydroxytryptamine (5-HT) as Peripheral Biomarker for the Depression Diagnosis and Response Evaluation to Antidepressants: Animal Experimental Study
Zuanjun Su 1, 2, Zhicong Chen 1, 2, Jinming Cao 1, 2, Canye Li 1, 2, Jingjing Duan 2, Ting Zhou 1, Zhen Yang 2, Yuanchi Cheng 2, Zhijun Xiao 1, Feng Xu 1*
1Fengxian Hospital & School of Pharmaceutical Science, Southern Medical University, Shanghai, China , 2Sixth People's Hospital South Campus, Shanghai Jiaotong University, Shanghai, China
Received: January 16, 2024; Revised: March 11, 2024; Accepted: March 29, 2024; Published online: March 29, 2024.
© The Korean College of Neuropsychopharmacology. All rights reserved.

Objective: Whether peripheral blood 5-hydroxytrptamine (5-HT) levels serve as biomarker for depression diagnosis/response evaluation has not been well determined. This work was explored to address this inconclusive issue.
Methods: Animals were randomized into control group (NC, n=10) and chronic stress model group (CUMS-model, n=20), respectively. Animals in CUMS-model group were subjected to chronic stress, then the modeled animals were randomly subdivided into CUMS subgroup and CUMS + fluoxetine subgroup (CUMS+FLX). After FLX treatment, blood and tissues were collected. 5-HT and relevant protein expression were measured.
Results: In mice model, there was a significant increase in serum 5-HT levels and a significant reduction in plasma 5-HT levels in CUMS-model group compared with NC group, while platelet 5-HT levels had not much change. After FLX treatment, serum and platelet 5-HT levels were significantly decreased in CUMS+FLX subgroup, while plasma 5-HT levels had not much change compared with CUMS subgroup. Chronic stress enhanced colon and platelet SERT expression and FLX treatment mitigated SERT expression. In rats’ model, there was a significant increase in serum 5-HT levels while plasma and platelet 5-HT levels showed little change in CUMS group compared with NC group. After FLX treatment, serum, plasma and platelet 5-HT levels were significantly decreased in CUMS + FLX subgroup compared with CUMS subgroup. The profile of relevant proteins expression changed by FLX were like those in mice.
Conclusion: Serum 5-HT levels might serve as a potential biomarker for depression diagnosis, meanwhile serum and platelet 5-HT levels might respond to antidepressant treatment.
Keywords: 5-HT, depression, biomarkers, chronic unpredictable mild stress (CUMS), fluoxetine