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/m 2 ; 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.
Pérez-Sánchez et al. (Wed,) studied this question.