BRIEF RESEARCH REPORT article
Front. Cell. Neurosci.
Sec. Cellular Neuropathology
Reduced Peripheral Serotonin Levels in Women with Multiple Sclerosis: Associations with Underweight Status, Treatment Duration, and Use of Interferon Beta 1a
Gilberto Pérez-Sánchez 1
León Arturo Aguilar Gómez 1
Giselle Berenice Vela Sancho 2
Salomón Jacinto-Gutiérrez 1
Enrique Becerril-Villanueva 1
Samantha Alvarez Herrera 1
Luis Alberto Vallejo-Castillo 3
Mario Alberto Mireles-Ramírez 4
María Paulina Reyes Mata 5
Jose de Jesus Guerrero-Garcia 6,7
Daniel Ortuño-Sahagún 8
Lenin Pavón 1
1. Laboratorio de Psicoinmunología, National Institute of Psychiatry Ramon de la Fuente Muñiz (INPRFM), Mexico City, Mexico
2. Laboratorio de Neuroinmunobiología Molecular, Universidad de Guadalajara Instituto de Neurociencias, Guadalajara, Mexico
3. Unidad de Desarrollo e Investigación en Bioterapéuticos (UDIBI), Instituto Politecnico Nacional Escuela Nacional de Ciencias Biologicas, Mexico City, Mexico
4. Unidad Médica de Alta Especialidad (UMAE), Hospital de Especialidades (HE),, Hospital de Especialidades del Centro Medico Nacional de Occidente IMSS, Guadalajara, Mexico
5. Departamento de Disciplinas Filosóficas, Metodológicas e Instrumentales. CUCS, Universidad de Guadalajara, Guadalajara, Mexico
6. Banco de Sangre Central, Unidad Médica de Alta Especialidad (UMAE), Hospital de Especialidades (HE),, Hospital de Especialidades del Centro Medico Nacional de Occidente IMSS, Guadalajara, Mexico
7. Departamento de Farmacobiología, Universidad de Guadalajara Centro Universitario de Ciencias Exactas e Ingenieria, Guadalajara, Mexico
8. Universidad de Guadalajara Instituto de Neurociencias, Guadalajara, Mexico
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Abstract
Multiple sclerosis (MS) is a chronic autoimmune-mediated demyelinating disease of the CNS, characterized by neuroinflammatory, axonal degeneration, and pronounced sexual dimorphism. Experimental data implicate dysregulated 5-HT levels in MS. However, the effects of clinical parameters and disease-modifying-therapies (DMTs) on peripheral 5-HT concentrations remain underexplored. This study aimed to quantify peripheral levels of tryptophan (Trp), 5-HT, and 5-hydroxyindoleacetic acid (5-HIAA) in patients with relapsing-remitting MS (RRMS) and to assess the effects of BMI, DMT duration, and specific DMT regimens. In this cross-sectional analysis, 226 participants were enrolled and stratified into four groups: healthy men (HM; n=29), healthy women (HW; n=84), men with RRMS (MMS; n=29), and women with RRMS (WMS; n=84). Serum concentrations of Trp, 5-HT, and 5-HIAA were measured using reverse-phase high-performance liquid chromatography (HPLC) with fluorescence detection. Nonparametric statistical tests were applied. Peripheral 5-HT levels were significantly reduced in underweight WMS (BMI <18 kg/m²; p<0.05), WMS with DMT duration over 4 years (p<0.01), and WMS receiving interferon beta-1a (p<0.01) compared to HW. No significant intergroup differences in Trp or 5-HIAA were observed across all stratifications. These findings reveal a novel association between reduced peripheral 5-HT and specific clinical-therapeutic factors in WMS, extending recent MS research on sex-specific vulnerabilities, serotonergic dysregulation in neuroinflammation, and psychiatric comorbidity. By highlighting the influence of low BMI, prolonged DMT exposure, and interferon beta-1a on 5-HT homeostasis, this study underscores the need for multidisciplinary management integrating neurological and psychiatric care in WMS and suggests avenues for precision interventions targeting serotonergic pathways to reduce disease burden.
Summary
Keywords
5-HIAA, interferon beta, Long-term treatment, Low weight, Multiple Sclerosis, RRMS, serotonin (5-HT), Tryptophan
Received
24 November 2025
Accepted
17 February 2026
Copyright
© 2026 Pérez-Sánchez, Aguilar Gómez, Vela Sancho, Jacinto-Gutiérrez, Becerril-Villanueva, Alvarez Herrera, Vallejo-Castillo, Mireles-Ramírez, Reyes Mata, Guerrero-Garcia, Ortuño-Sahagún and Pavón. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Lenin Pavón
Disclaimer
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