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.