Maurizio Pompili1, Luana Lionetto2, Martina Curto3, Alberto Forte3, Denise Erbuto3, Franco Montebovi3, Maria Elena Seretti3, Isabella Berardelli3, Gianluca Serafini4,5, Marco Innamorati6, Mario Amore4,5, Ross J Baldessarini7,8, Paolo Girardi3, Maurizio Simmaco2. 1. Department of Neurosciences, Mental Health and Sensory Organs, Suicide Prevention Center, Sant'Andrea Hospital, Sapienza University of Rome, Rome, Italymaurizio.pompili@uniroma1.it. 2. Advanced Molecular Diagnostics Unit, Sant'Andrea Hospital, Sapienza University of Rome, Rome, Italy. 3. Department of Neurosciences, Mental Health and Sensory Organs, Suicide Prevention Center, Sant'Andrea Hospital, Sapienza University of Rome, Rome, Italy. 4. Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DINOGMI), Section of Psychiatry, University of Genoa, Genoa, Italy. 5. IRCCS Ospedale Policlinico San Martino, Genoa, Italy. 6. Department of Human Sciences, European University of Rome, Rome, Italy. 7. International Consortium for Mood and Psychotic Disorders Research, Mailman Research Center, McLean Hospital, Belmont, Massachusetts, USA. 8. Department of Psychiatry, Harvard Medical School, Boston, Massachusetts, USA.
Abstract
BACKGROUND: Some previous studies found decreased concentrations of L-tryptophan (TRY) and increased L-kynurenine (KYN), or its metabolites, in the body fluids of subjects with major depressive disorder (MDD), sometimes in association with suicidal behavior. Such changes might indicate a shift of TRY away from serotonin production, possibly via the effects of inflammatory peptides which activate indoleamine-2,3-dioxygenase. However, these findings have been inconsistent and require replication. METHODS: We used sensitive liquid-chromatography mass spectrometry methods to assay plasma concentrations of TRY, 5-hydroxyindoleacetic acid (5-HIAA), and KYN and its metabolites (anthranilic acid and xanthurenic acid). We compared 49 hospitalized, depressed subjects diagnosed with MDD (n = 37) or bipolar disorder (BD, n = 12), with (n = 22) or without (n = 27) previous suicide attempts, to 78 healthy, ambulatory controls of similar age and sex (total n = 127). FINDINGS: Contrary to expectation, TRY plasma concentrations were higher, KYN plasma concentrations were lower, and their ratio much higher in depressed subjects, with no relationship to suicidal history. Concentrations of 5-HIAA and the kynurenine metabolites did not differ between depressed and healthy subjects. CONCLUSIONS: These findings are opposite to expectations and not consistent with a hypothesized increased conversion from TRY to KYN in depressed subjects. In addition, we found no evidence of altered production of serotonin as 5-HIAA concentration was unchanged. None of the observed changes was associated with a history of suicide attempt.
BACKGROUND: Some previous studies found decreased concentrations of L-tryptophan (TRY) and increased L-kynurenine (KYN), or its metabolites, in the body fluids of subjects with major depressive disorder (MDD), sometimes in association with suicidal behavior. Such changes might indicate a shift of TRY away from serotonin production, possibly via the effects of inflammatory peptides which activate indoleamine-2,3-dioxygenase. However, these findings have been inconsistent and require replication. METHODS: We used sensitive liquid-chromatography mass spectrometry methods to assay plasma concentrations of TRY, 5-hydroxyindoleacetic acid (5-HIAA), and KYN and its metabolites (anthranilic acid and xanthurenic acid). We compared 49 hospitalized, depressed subjects diagnosed with MDD (n = 37) or bipolar disorder (BD, n = 12), with (n = 22) or without (n = 27) previous suicide attempts, to 78 healthy, ambulatory controls of similar age and sex (total n = 127). FINDINGS: Contrary to expectation, TRY plasma concentrations were higher, KYN plasma concentrations were lower, and their ratio much higher in depressed subjects, with no relationship to suicidal history. Concentrations of 5-HIAA and the kynurenine metabolites did not differ between depressed and healthy subjects. CONCLUSIONS: These findings are opposite to expectations and not consistent with a hypothesized increased conversion from TRY to KYN in depressed subjects. In addition, we found no evidence of altered production of serotonin as 5-HIAA concentration was unchanged. None of the observed changes was associated with a history of suicide attempt.
Authors: Eva Z Reininghaus; Nina Dalkner; Karin Riedrich; Dietmar Fuchs; Johanna M Gostner; Bernd Reininghaus Journal: Front Psychiatry Date: 2019-02-21 Impact factor: 4.157
Authors: Patrick Mucher; Delgerdalai Batmyagmar; Thomas Perkmann; Manuela Repl; Astrid Radakovics; Elisabeth Ponocny-Seliger; Ina Lukas; Monika Fritzer-Szekeres; Johann Lehrner; Thomas Knogler; Dimiter Tscholakoff; Martina Fondi; Oswald F Wagner; Robert Winker; Helmuth Haslacher Journal: Psychophysiology Date: 2021-03-02 Impact factor: 4.016
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