Serotonin is a neurotransmiter involved in many physiological processes. It affects sleep, mood, circadian rhythm, appetite, metabolic regulations, as well as the response to many drugs and medicines. Its metabolism, closely related to melatonin, involves key enzymes (e.g. cytochrome P450) exhibiting inter and intra-individual functional variability.
To date, no endogenous substrate is validated as test probe. The in vivo determination of enzymatic activity needs time consuming procedures with probe substance administration under controlled conditions. Determining enzyme activity from endogenous serotonin metabolites and ratio calculations on a single blood/urine sample could offer new diagnostic tools regarding serotonin-related diseases, neurocognitive processes and pharmacogenetic traits. Moreover, serotonin is produced by carcinoid tumors, a rare form of cancer difficult to diagnose with the currently available, suboptimal markers. Screening blood and urine serotonin metabolites may thus also allow identifying new biomarkers of these specific tumors.
Concretely, this project aims (1) to measure an array of serotonin metabolites in humans, (2) to define normal ranges for these metabolites and their ratios in healthy volunteers, (3) to identify potential candidate metabolites that would better perform as biomarkers for carcinoid tumor diagnosis, (4) to assess the influence of drugs affecting serotoninergic transmission or biotransformation on these metabolites, (5) to determine whether their concentrations are modulated during pathological conditions such as serotoninergic syndrome, (6) to correlate the activity of genetically polymorphic enzymes with the measurement of endogenous metabolites.