Genetic Polymorphism Associated Prefrontal Glutathione and Its Coupling With Brain Glutamate and Peripheral Redox Status in Early Psychosis.

Details

Ressource 1Download: 27069063.pdf (1370.30 [Ko])
State: Public
Version: Author's accepted manuscript
Serval ID
serval:BIB_C3341BECC5AD
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Genetic Polymorphism Associated Prefrontal Glutathione and Its Coupling With Brain Glutamate and Peripheral Redox Status in Early Psychosis.
Journal
Schizophrenia bulletin
Author(s)
Xin L., Mekle R., Fournier M., Baumann P.S., Ferrari C., Alameda L., Jenni R., Lu H., Schaller B., Cuenod M., Conus P., Gruetter R., Do K.Q.
ISSN
1745-1701 (Electronic)
ISSN-L
0586-7614
Publication state
Published
Issued date
09/2016
Peer-reviewed
Oui
Volume
42
Number
5
Pages
1185-1196
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Abstract
Oxidative stress and glutathione (GSH) metabolism dysregulation has been implicated in the pathophysiology of schizophrenia. GAG-trinucleotide repeat (TNR) polymorphisms in the glutamate-cysteine ligase catalytic gene (GCLC), the rate-limiting enzyme for GSH synthesis, are associated with schizophrenia. In addition, GSH may serve as a reserve pool for neuronal glutamate (Glu) through the γ-glutamyl cycle. The aim of this study is to investigate brain [GSH] and its association with GCLC polymorphism, peripheral redox indices and brain Glu.
Magnetic resonance spectroscopy was used to measure [GSH] and [Glu] in the medial prefrontal cortex (mPFC) of 25 early-psychosis patients and 33 controls. GCLC polymorphism was genotyped, glutathione peroxidases (GPx) and glutathione reductase (GR) activities were determined in blood cells.
Significantly lower [GSHmPFC] in GCLC high-risk genotype subjects were revealed as compared to low-risk genotype subjects independent of disease status. In male subjects, [GSHmPFC] and blood GPx activities correlate positively in controls (P = .021), but negatively in patients (P = .039). In GCLC low-risk genotypes, [GlumPFC] are lower in patients, while it is not the case for high-risk genotypes.
GCLC high-risk genotypes are associated with low [GSHmPFC], highlighting that GCLC polymorphisms should be considered in pathology studies of cerebral GSH. Low brain GSH levels are related to low peripheral oxidation status in controls but with high oxidation status in patients, pointing to a dysregulated GSH homeostasis in early psychosis patients. GCLC polymorphisms and disease associated correlations between brain GSH and Glu levels may allow patients stratification.

Keywords
Adult, Female, Genotype, Glutamate-Cysteine Ligase/genetics, Glutamic Acid/metabolism, Glutathione/metabolism, Glutathione Peroxidase/metabolism, Humans, Magnetic Resonance Spectroscopy, Male, Oxidation-Reduction, Oxidative Coupling, Polymorphism, Genetic, Prefrontal Cortex/diagnostic imaging, Prefrontal Cortex/metabolism, Psychotic Disorders/diagnostic imaging, Psychotic Disorders/metabolism, Young Adult, GCLC, MRS, glutamate, glutathione, glutathione peroxidase, oxidative stress, redox, schizophrenia
Pubmed
Web of science
Open Access
Yes
Create date
25/04/2016 13:37
Last modification date
20/08/2019 16:38
Usage data