Kynurenine pathway and white matter microstructure in bipolar disorder

S Poletti, AM Myint, G Schüetze, I Bollettini, E Mazza, D Grillitsch, C Locatelli, M Schwarz, C Colombo, F Benedetti

Research output: Contribution to journalArticle

Abstract

Decreased availability of serotonin in the central nervous system has been suggested to be a central factor in the pathogenesis of depression. Activation of indoleamine 2–3 dioxygenase following a pro-inflammatory state could reduce the amount of tryptophan converted to serotonin and increase the production of tryptophan catabolites such as kynurenic acid, an antagonist of ionotropic excitatory aminoacid receptors, whose levels are reduced in bipolar disorder. Abnormalities in white matter (WM) integrity have been widely reported in BD. We then hypothesized that metabolites involved in serotoninergic turnover in BD could influence DTI measures of WM microstructure. Peripheral levels of tryptophan, kynurenine, kynurenic acid, 3-hydroxy-kynurenine, and 5-HIAA were analysed in 22 patients affected by BD and 15 healthy controls. WM microstructure was evaluated using diffusion tensor imaging and tract-based spatial statistics with threshold-free cluster enhancement only in bipolar patients. We observed that kynurenic acid and 5-HIAA were reduced in BD and associated with DTI measures of WM integrity in several association fibres: inferior and superior longitudinal fasciculus, cingulum bundle, corpus callosum, uncus, anterior thalamic radiation and corona radiata. Our results seem to suggest that higher levels of 5-HIAA, a measure of serotonin levels, and higher levels of kynurenic acid, which protects from glutamate excitotoxicity, could exert a protective effect on WM microstructure. Reduced levels of these metabolites in BD thus seem to confirm a crucial role of serotonin turnover in BD pathophysiology. © 2016 Springer-Verlag Berlin Heidelberg
Original languageEnglish
Pages (from-to)157-168
Number of pages12
JournalEuropean Archives of Psychiatry and Clinical Neuroscience
Volume268
Issue number2
DOIs
Publication statusPublished - 2018

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Kynurenine
Kynurenic Acid
Bipolar Disorder
Hydroxyindoleacetic Acid
Serotonin
Tryptophan
Dioxygenases
Diffusion Tensor Imaging
Corpus Callosum
Berlin
Glutamic Acid
Central Nervous System
White Matter
Radiation
Depression

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Kynurenine pathway and white matter microstructure in bipolar disorder. / Poletti, S; Myint, AM; Schüetze, G; Bollettini, I; Mazza, E; Grillitsch, D; Locatelli, C; Schwarz, M; Colombo, C; Benedetti, F.

In: European Archives of Psychiatry and Clinical Neuroscience, Vol. 268, No. 2, 2018, p. 157-168.

Research output: Contribution to journalArticle

Poletti, S ; Myint, AM ; Schüetze, G ; Bollettini, I ; Mazza, E ; Grillitsch, D ; Locatelli, C ; Schwarz, M ; Colombo, C ; Benedetti, F. / Kynurenine pathway and white matter microstructure in bipolar disorder. In: European Archives of Psychiatry and Clinical Neuroscience. 2018 ; Vol. 268, No. 2. pp. 157-168.
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