Tryptophan and Kynurenine Metabolites: Are They Related to Depression?
Depression
Kynurenine
Serotonin
Suicide
Tryptophan
Journal
Neuropsychobiology
ISSN: 1423-0224
Titre abrégé: Neuropsychobiology
Pays: Switzerland
ID NLM: 7512895
Informations de publication
Date de publication:
2019
2019
Historique:
received:
02
01
2018
accepted:
28
06
2018
pubmed:
16
8
2018
medline:
12
12
2018
entrez:
16
8
2018
Statut:
ppublish
Résumé
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. 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). 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. 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.
Sections du résumé
BACKGROUND
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
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
RESULTS
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
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.
Identifiants
pubmed: 30110684
pii: 000491604
doi: 10.1159/000491604
doi:
Substances chimiques
Xanthurenates
0
ortho-Aminobenzoates
0
anthranilic acid
0YS975XI6W
Kynurenine
343-65-7
Hydroxyindoleacetic Acid
54-16-0
xanthurenic acid
58LAB1BG8J
Tryptophan
8DUH1N11BX
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
23-28Informations de copyright
© 2018 S. Karger AG, Basel.