N-acetylcysteine in a Double-Blind Randomized Placebo-Controlled Trial: Toward Biomarker-Guided Treatment in Early Psychosis.

Details

Ressource 1Download: sbx093.pdf (1997.08 [Ko])
State: Public
Version: Final published version
Serval ID
serval:BIB_8CA869F64DD6
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
N-acetylcysteine in a Double-Blind Randomized Placebo-Controlled Trial: Toward Biomarker-Guided Treatment in Early Psychosis.
Journal
Schizophrenia bulletin
Author(s)
Conus P., Seidman L.J., Fournier M., Xin L., Cleusix M., Baumann P.S., Ferrari C., Cousins A., Alameda L., Gholam-Rezaee M., Golay P., Jenni R., Woo T.W., Keshavan M.S., Eap C.B., Wojcik J., Cuenod M., Buclin T., Gruetter R., Do K.Q.
ISSN
1745-1701 (Electronic)
ISSN-L
0586-7614
Publication state
Published
Issued date
15/02/2018
Peer-reviewed
Oui
Volume
44
Number
2
Pages
317-327
Language
english
Notes
Publication types: Journal Article ; Multicenter Study ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
Biomarker-guided treatments are needed in psychiatry, and previous data suggest oxidative stress may be a target in schizophrenia. A previous add-on trial with the antioxidant N-acetylcysteine (NAC) led to negative symptom reductions in chronic patients. We aim to study NAC's impact on symptoms and neurocognition in early psychosis (EP) and to explore whether glutathione (GSH)/redox markers could represent valid biomarkers to guide treatment. In a double-blind, randomized, placebo-controlled trial in 63 EP patients, we assessed the effect of NAC supplementation (2700 mg/day, 6 months) on PANSS, neurocognition, and redox markers (brain GSH [GSHmPFC], blood cells GSH levels [GSHBC], GSH peroxidase activity [GPxBC]). No changes in negative or positive symptoms or functional outcome were observed with NAC, but significant improvements were found in favor of NAC on neurocognition (processing speed). NAC also led to increases of GSHmPFC by 23% (P = .005) and GSHBC by 19% (P = .05). In patients with high-baseline GPxBC compared to low-baseline GPxBC, subgroup explorations revealed a link between changes of positive symptoms and changes of redox status with NAC. In conclusion, NAC supplementation in a limited sample of EP patients did not improve negative symptoms, which were at modest baseline levels. However, NAC led to some neurocognitive improvements and an increase in brain GSH levels, indicating good target engagement. Blood GPx activity, a redox peripheral index associated with brain GSH levels, could help identify a subgroup of patients who improve their positive symptoms with NAC. Thus, future trials with antioxidants in EP should consider biomarker-guided treatment.
Keywords
Acetylcysteine/administration & dosage, Acetylcysteine/pharmacology, Adolescent, Adult, Antioxidants/administration & dosage, Antioxidants/pharmacology, Biomarkers, Cognitive Dysfunction/drug therapy, Cognitive Dysfunction/etiology, Cognitive Dysfunction/metabolism, Cognitive Dysfunction/physiopathology, Double-Blind Method, Female, Glutathione/drug effects, Glutathione Peroxidase, Humans, Magnetic Resonance Spectroscopy, Male, Outcome Assessment (Health Care), Oxidation-Reduction, Prefrontal Cortex/drug effects, Prefrontal Cortex/metabolism, Psychotic Disorders/complications, Psychotic Disorders/drug therapy, Psychotic Disorders/metabolism, Psychotic Disorders/physiopathology, Schizophrenia/complications, Schizophrenia/drug therapy, Schizophrenia/metabolism, Schizophrenia/physiopathology, Young Adult
Pubmed
Web of science
Open Access
Yes
Create date
06/07/2017 8:41
Last modification date
20/08/2019 14:50
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