Role of serotonin and serotonergic-related metabolites in the pathogenesis of vasovagal syncope.

Background: Serotonin is an important neurohormone that regulates vascular tone and autonomic reflexes, though its pathophysiological role in vasovagal syncope (VVS) remains uncertain.

Objective: This study sought to explore the involvement of serotonin and serotonergic-related metabolites in the pathogenesis of VVS.

Methods: Sixty-six patients [mean age 45.6±17.0 years; 33 women (50%)] with recurrent VVS underwent a head-up tilt test (HUTT). Blood samples were collected from all patients in a resting supine position, with an additional sample obtained from HUTT-positive patients during syncope. Plasma and platelet serotonin levels and plasma concentrations of serotonergic-related metabolites-including serotonin's precursor 5-hydroxytryptophan (5-HTP), major metabolite 5-hydroxyindoleacetic acid, and synthesis source tryptophan-were measured using the liquid chromatography tandem mass spectrometry method.

Results: HUTT was positive in 45 (68.2%) patients and negative in 21 (21.8%) patients. Significant differences were observed in plasma 5-HTP and 5-hydroxyindoleacetic acid levels between HUTT-positive and HUTT-negative patients (P<.001 and P=.040, respectively) as well as before and after syncope (P<.001 for all), whereas no significant changes were found in serotonin and tryptophan levels. Notably, plasma serotonin levels significantly increased during syncope in patients with drug-free VVS (P=.037), and a greater change in serotonin correlated with a shorter time to syncope (R=0.38; P=.015). Furthermore, certain serotonergic-related metabolites exhibited significant correlations with hemodynamic changes during VVS episodes, with 5-HTP demonstrating the highest sensitivity.

Conclusion: Despite the unchanged plasma and platelet serotonin levels, certain serotonergic-related metabolites significantly changed and correlated with hemodynamic parameters during VVS episodes, suggesting the potential involvement of an altered serotonergic metabolic pathway in VVS.