000218095 001__ 218095
000218095 005__ 20190317000427.0
000218095 0247_ $$2doi$$a10.1093/schbul/sbw038
000218095 022__ $$a1745-1701
000218095 02470 $$2ISI$$a000386209900015
000218095 037__ $$aARTICLE
000218095 245__ $$aGenetic Polymorphism Associated Prefrontal Glutathione and Its Coupling With Brain Glutamate and Peripheral Redox Status in Early Psychosis
000218095 260__ $$bOxford University Press$$c2016$$aOxford
000218095 269__ $$a2016
000218095 300__ $$a12
000218095 336__ $$aJournal Articles
000218095 520__ $$aBACKGROUND: 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 gamma-glutamyl cycle. The aim of this study is to investigate brain [GSH] and its association with GCLC polymorphism, peripheral redox indices and brain Glu. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
000218095 6531_ $$aCIBM-AIT
000218095 700__ $$0243883$$g169484$$aXin, Lijing
000218095 700__ $$0243740$$g169551$$aMekle, Ralf
000218095 700__ $$aFournier, Margot
000218095 700__ $$aBaumann, Philipp S
000218095 700__ $$aFerrari, Carina
000218095 700__ $$aAlameda, Luis
000218095 700__ $$aJenni, Raoul
000218095 700__ $$aLu, Huanxiang
000218095 700__ $$0243719$$g166802$$aSchaller, Benoit
000218095 700__ $$aCuenod, Michel
000218095 700__ $$aConus, Philippe
000218095 700__ $$0243712$$g161735$$aGruetter, Rolf
000218095 700__ $$aDo, Kim Q
000218095 773__ $$j42$$tSchizophrenia bulletin$$k5$$q1185-1196
000218095 8564_ $$uhttps://infoscience.epfl.ch/record/218095/files/Lijing_SchizBull_2016.pdf$$zPublisher's version$$s1860633$$yPublisher's version
000218095 909C0 $$xU10984$$0252276$$pLIFMET
000218095 909C0 $$pCIBM$$xU12623$$0252477
000218095 909CO $$qGLOBAL_SET$$pSB$$particle$$ooai:infoscience.tind.io:218095
000218095 917Z8 $$x161735
000218095 917Z8 $$x161735
000218095 937__ $$aEPFL-ARTICLE-218095
000218095 973__ $$rREVIEWED$$sPUBLISHED$$aEPFL
000218095 980__ $$aARTICLE