Feasibility of Using Serum, Plasma, and Platelet 5-hydroxytryptamine as Peripheral Biomarker for the Depression Diagnosis and Response Evaluation to Antidepressants: Animal Experimental Study
Zuanjun Su1,2,*, Zhicong Chen1,2,*, Jinming Cao1,2, Canye Li1,2, Jingjing Duan2, Ting Zhou1, Zhen Yang2, Yuanchi Cheng2, Zhijun Xiao1, Feng Xu1
1Department of Clinical Pharmacy, Fengxian Hospital and School of Pharmaceutical Science, Southern Medical University, Shanghai, China
2Department of Pharmacology, Sixth People’s Hospital South Campus, Shanghai Jiaotong University, Shanghai, China
Correspondence to: Feng Xu
Department of Clinical Pharmacy, Fengxian Hospital and School of Pharmaceutical Science, Southern Medical University, 6600 Nanfeng Hwy, Shanghai 201499, China
E-mail: xuf@smu.edu.cn
ORCID: https://orcid.org/0000-0001-6215-8696

*These authors contributed equally to this study.
Received: January 18, 2024; Revised: March 11, 2024; Accepted: March 29, 2024; Published online: May 3, 2024.
© The Korean College of Neuropsychopharmacology. All rights reserved.

This is an Open-Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract
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 normal control group (NC, n = 10) and chronic unpredictable mild stress model group (CUMS-model, n = 20), respectively. Animals in CUMS-model group were subjected to chronic stress, then they 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 and a significant reduction in plasma 5-HT levels in CUMS-model group versus NC group, while platelet 5-HT levels change little. 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 versus CUMS subgroup. Chronic stress enhanced colon and platelet serotonin transporter (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 versus NC group. After FLX treatment, serum, plasma and platelet 5-HT levels were significantly decreased in CUMS + FLX subgroup versus 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: Serotonin; Depression; Biomarkers; Chronic unpredictable mild stress; Fluoxetine


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