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

Détails

Ressource 1Télécharger: sbx093.pdf (1997.08 [Ko])
Etat: Public
Version: Final published version
ID Serval
serval:BIB_8CA869F64DD6
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
N-acetylcysteine in a Double-Blind Randomized Placebo-Controlled Trial: Toward Biomarker-Guided Treatment in Early Psychosis.
Périodique
Schizophrenia bulletin
Auteur(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
Statut éditorial
Publié
Date de publication
15/02/2018
Peer-reviewed
Oui
Volume
44
Numéro
2
Pages
317-327
Langue
anglais
Notes
Publication types: Journal Article ; Multicenter Study ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
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.
Mots-clé
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
Oui
Création de la notice
06/07/2017 9:41
Dernière modification de la notice
20/08/2019 15:50
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