N-acetylcysteine in a Double-Blind Randomized Placebo-Controlled Trial: Toward Biomarker-Guided Treatment in Early Psychosis
| Autor: | Matcheri S. Keshavan, Martine Cleusix, Raoul Jenni, Michel Cuenod, Philippe Conus, Kim Q. Do, Lijing Xin, Luis Alameda, Chin B. Eap, Rolf Gruetter, T-U Wilson Woo, Philippe Golay, Larry J. Seidman, Thierry Buclin, Philipp S. Baumann, Carina Ferrari, Margot Fournier, Joanne Wojcik, Mehdi Gholam-Rezaee, Ann Cousins |
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| Rok vydání: | 2018 |
| Předmět: |
Adult
Male medicine.medical_specialty MRS Magnetic Resonance Spectroscopy Adolescent neurocognition Placebo-controlled study Prefrontal Cortex Pharmacology medicine.disease_cause Acetylcysteine/administration & dosage Acetylcysteine/pharmacology 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 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 Antioxidants law.invention Acetylcysteine 03 medical and health sciences 0302 clinical medicine Randomized controlled trial law Outcome Assessment Health Care medicine Cognitive Dysfunction glutathione Psychiatry glutathione peroxidase chemistry.chemical_classification Glutathione peroxidase Gamma hydroxybutyrate medicine.disease 3. Good health 030227 psychiatry schizophrenia Psychiatry and Mental health chemistry Psychotic Disorders Schizophrenia Biomarker (medicine) Psychology 030217 neurology & neurosurgery Oxidative stress medicine.drug Regular Articles |
| Zdroj: | Schizophrenia Bulletin Schizophrenia bulletin, vol. 44, no. 2, pp. 317-327 |
| ISSN: | 1745-1701 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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