FEASIBILITY OF USING SERUM, PLASMA, AND PLATELET 5- HYDROXYTRYPTAMIN (5-HT) AS PERIPHERAL BIOMARKER FOR THE DEPRESSION DIAGNOSIS AND RESPONSE EVALUATION TO ANTIDEPRESSANT
Authors: Xu *Feng , Sun Zuanjun 
Published: February 2025

Abstract

Background
There is a problem of result inconsistency between peripheral 5-HT levels and the depression diagnosis and response evaluation to antidepressant both in clinical evidence and animal experiments.

Aims & Objectives
This article explores the feasibility of using serum, plasma, and platelet 5-HT levels as biomarkers for the diagnosis and response evaluation with animal depression models.

Methods
The animal experiments were conducted using female C57BL/6 mice and female SD rats, respectively. The animals were randomized into 2 groups, control group (NC, n=10), and chronic stress model group (CUMS model, n=20). Animals in NC group were fed freely. Animals in CUMS-model group were first subjected to chronic stress for 4 weeks for mice and 15 weeks for rats, respectively, to induce depression-like behavior. At the end of model establishment, blood was collected. The successful model animals were randomly divided into 2 groups, CUMS subgroup (n=10), and CUMS + fluoxetine subgroup (CUMS&FLX, n=10). Then the animals in NC group/ CUMS group and in CUMS&FLX group were given water and FLX (10mg/kg) respectively for 4 weeks, finally followed by cervical dislocation and blood collection. LC-MS/MS was used to detect the levels of 5-HT in peripheral samples. Some tissues were collected to measure relevant protein expression with Western blotting.

Results
Behavioral test confirmed the chronic stress-induced depression-like models were successfully established in two animals. After fluoxetine treatment, depression-like behaviors were improved, and body weights were increased in two models. 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 (p&lt;0.05) compared with the NC group, while platelet 5-HT levels had not much change. After treatment, serum 5-HT levels and platelet 5-HT levels were significantly decreased in CUMS&FLX group (p&lt;0.01), while plasma 5-HT levels had not much change compared with the CUMS group. Further study showed that chronic stress enhanced colon and platelet SERT expression and FLX treatment mitigated SERT expression in mice model. In rats model: there was a significant increase in serum 5-HT levels while plasma and platelet 5-HT levels showed little change in the CUMS group (p&lt;0.01) compared with the NC group. After treatment, serum and platelet 5- HT levels significantly decreased, while plasma 5-HT levels decreased slightly in CUMS&FLX group (p&lt;0.01) compared with the CUMS group. The relevant proteins in rat tissues were like those in mice.

Discussion & Conclusions
Although these peripheral index are not direct reflectors of central 5-HT levels, increased serum 5-HT level might be feasible to serve as a potential biomarker for diagnosis of depression, meanwhile decreased serum 5-HT and platelet 5-HT levels might respond to SSRI treatment.

References
Li C, Cai Q, Su Z, Chen Z, Cao J, Xu F. Could peripheral 5-HT level be used as a biomarker for depression diagnosis and treatment? A narrative minireview. Front Pharmacol 2023; 14, 1149511.