title: Glutathione precursor N-acetyl-cysteine modulates EEG synchronization in schizophrenia patients: a double-blind, randomized, placebo-controlled trial.
abstract: Glutathione (GSH) dysregulation at the gene, protein, and functional levels has been observed in schizophrenia patients. Together with disease-like anomalies in GSH deficit experimental models, it suggests that such redox dysregulation can play a critical role in altering neural connectivity and synchronization, and thus possibly causing schizophrenia symptoms. To determine whether increased GSH levels would modulate EEG synchronization, N-acetyl-cysteine (NAC), a glutathione precursor, was administered to patients in a randomized, double-blind, crossover protocol for 60 days, followed by placebo for another 60 days (or vice versa). We analyzed whole-head topography of the multivariate phase synchronization (MPS) for 128-channel resting-state EEGs that were recorded at the onset, at the point of crossover, and at the end of the protocol. In this proof of concept study, the treatment with NAC significantly increased MPS compared to placebo over the left parieto-temporal, the right temporal, and the bilateral prefrontal regions. These changes were robust both at the group and at the individual level. Although MPS increase was observed in the absence of clinical improvement at a group level, it correlated with individual change estimated by Liddle's disorganization scale. Therefore, significant changes in EEG synchronization induced by NAC administration may precede clinically detectable improvement, highlighting its possible utility as a biomarker of treatment efficacy.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT01506765.
authors.affiliation: Center for Psychiatric Neuroscience, Department of Psychiatry, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Lausanne, Switzerland.
authors.forename: Cristian
authors.initials: C
authors.lastname: Carmeli
authors.forename: Maria G
authors.initials: MG
authors.lastname: Knyazeva
authors.forename: Michel
authors.initials: M
authors.lastname: Cuénod
authors.forename: Kim Q
authors.initials: KQ
authors.lastname: Do
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology*; D000328:Adult; D015415:Biomarkers; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004569:Electroencephalography / Q000379:methods*; D005260:Female; D016166:Free Radical Scavengers / Q000494:pharmacology*; D005978:Glutathione / Q000378:metabolism*; D006801:Humans; D008297:Male; D015233:Models, Statistical; D015999:Multivariate Analysis; D009991:Oscillometry; D010084:Oxidation-Reduction; D010919:Placebos; D012559:Schizophrenia / Q000188:drug therapy* / Q000503:physiopathology; D012815:Signal Processing, Computer-Assisted
chemical_list: D015415:Biomarkers; D016166:Free Radical Scavengers; D010919:Placebos; D005978:Glutathione; D000111:Acetylcysteine