Romain Colle1,2, Perrine Masson3, Céline Verstuyft1,4, Bruno Fève5,6, Erwan Werner3, Claire Boursier-Neyret3, Bernard Walther3, Denis J David1, Bruno Boniface1, Bruno Falissard1,7, Philippe Chanson8, Emmanuelle Corruble1,2, Laurent Becquemont1,4. 1. INSERM UMR-1178, CESP, Faculté de Médecine Paris-Sud, Paris-Saclay University, Le Kremlin Bicêtre, France. 2. Service Hospitalo-Universitaire de Psychiatrie, Assistance Publique-Hôpitaux de Paris, Hôpitaux Universitaires Paris-Sud, Hôpital de Bicêtre, Le Kremlin Bicêtre, France. 3. Pharmacokinetics Center, Technologie Servier, Orléans, France. 4. Service de Génétique moléculaire, Pharmacogénétique et Hormonologie, Assistance Publique-Hôpitaux de Paris, Hôpitaux Universitaires Paris-Sud, Hôpital de Bicêtre, Le Kremlin Bicêtre, France. 5. Service d'endocrinologie, Hôpital Saint-Antoine, Assistance Publique Hôpitaux de Paris, Paris, France. 6. Sorbonne Université, INSERM UMR S_938, Centre de Recherche Saint-Antoine, Paris, France. 7. Département de Biostatistiques, Paris-Sud University, Hôpital Paul Brousse, Assistance Publique Hôpitaux de Paris, Villejuif, France. 8. Assistance Publique-Hôpitaux de Paris, Hôpital de Bicêtre, Service d'Endocrinologie et des Maladies de la Reproduction, Centre de Référence des Maladies Rares de l'Hypophyse, Le Kremlin Bicêtre, F-94275, and INSERM 1185, Faculté de Médecine Paris-Sud, Paris-Sud University, Paris-Saclay University, Le Kremlin-Bicêtre, France.
Abstract
AIM: Tryptophan is the sole precursor of both peripherally and centrally produced serotonin and kynurenine. In depressed patients, tryptophan, serotonin, kynurenine, and their metabolite levels remain unclear. Therefore, peripheral tryptophan and metabolites of serotonin and kynurenine were investigated extensively in 173 patients suffering from a current major depressive episode (MDE) and compared to 214 healthy controls (HC). METHODS: Fasting plasma levels of 11 peripheral metabolites were quantified: tryptophan, serotonin pathway (serotonin, its precursor 5-hydroxytryptophan and its metabolite 5-hydroxyindoleacetic acid), and kynurenine pathway (kynurenine and six of its metabolites: anthranilic acid, kynurenic acid, nicotinamide, picolinic acid, xanthurenic acid, and 3-hydroxyanthranilic acid). RESULTS: Sixty (34.7%) patients were antidepressant-drug free. Tryptophan levels did not differ between MDE patients and HC. Serotonin and its precursor (5-hydroxytryptophan) levels were lower in MDE patients than in HC, whereas, its metabolite (5-hydroxyindoleacetic acid) levels were within the standard range. Kynurenine and four of its metabolites (kynurenic acid, nicotinamide, picolinic acid, and xanthurenic acid) were lower in MDE patients. CONCLUSION: Whilst the results of this study demonstrate an association between the metabolites studied and depression, conclusions about causality cannot be made. This study uses the largest ever sample of MDE patients, with an extensive assessment of peripheral tryptophan metabolism in plasma. These findings provide new insights into the peripheral signature of MDE. The reasons for these changes should be further investigated. These results might suggest new antidepressant therapeutic strategies.
AIM: Tryptophan is the sole precursor of both peripherally and centrally produced serotonin and kynurenine. In depressedpatients, tryptophan, serotonin, kynurenine, and their metabolite levels remain unclear. Therefore, peripheral tryptophan and metabolites of serotonin and kynurenine were investigated extensively in 173 patients suffering from a current major depressive episode (MDE) and compared to 214 healthy controls (HC). METHODS: Fasting plasma levels of 11 peripheral metabolites were quantified: tryptophan, serotonin pathway (serotonin, its precursor 5-hydroxytryptophan and its metabolite 5-hydroxyindoleacetic acid), and kynurenine pathway (kynurenine and six of its metabolites: anthranilic acid, kynurenic acid, nicotinamide, picolinic acid, xanthurenic acid, and 3-hydroxyanthranilic acid). RESULTS: Sixty (34.7%) patients were antidepressant-drug free. Tryptophan levels did not differ between MDE patients and HC. Serotonin and its precursor (5-hydroxytryptophan) levels were lower in MDE patients than in HC, whereas, its metabolite (5-hydroxyindoleacetic acid) levels were within the standard range. Kynurenine and four of its metabolites (kynurenic acid, nicotinamide, picolinic acid, and xanthurenic acid) were lower in MDE patients. CONCLUSION: Whilst the results of this study demonstrate an association between the metabolites studied and depression, conclusions about causality cannot be made. This study uses the largest ever sample of MDE patients, with an extensive assessment of peripheral tryptophan metabolism in plasma. These findings provide new insights into the peripheral signature of MDE. The reasons for these changes should be further investigated. These results might suggest new antidepressant therapeutic strategies.
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Authors: Johann Steiner; Henrik Dobrowolny; Paul C Guest; Hans-Gert Bernstein; Dietmar Fuchs; Julien Roeser; Paul Summergrad; Gregory F Oxenkrug Journal: Int J Tryptophan Res Date: 2021-05-19