Glutathione precursor N-acetyl-cysteine modulates EEG synchronization in schizophrenia patients: a double-blind, randomized, placebo-controlled trial
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UNLABELLED: 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. TRIAL REGISTRATION: ClinicalTrials.gov NCT01506765.
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NAC raised phase synchronization of neuronal activity in left parieto-temporal, right temporal, and bilateral prefrontal areas.
“NAC also increased phase synchronization of neuronal activity over the left parieto-temporal, the right temporal, and the bilateral prefrontal regions (Carmeli et al., 2012).”
From Redox dysregulation, neuroinflammation, and NMDA receptor hypofunction: A “central hub” in schizophrenia pathophysiology? (2016) · cites this paper as Carmeli et al., 2012
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- Authors
- Carmeli, C., Knyazeva, M. G., Cuénod, M., & Do, K. Q.
- Affiliations
- Centre Hospitalier Universitaire Vaudois (CH)
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2012-02-22
- Volume
- 7
- Issue
- 2
- Pages
- e29341
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC3285150
- OpenAlex
- W1996517171
- Cited by
- 81
- References
- 82
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 4 · 2023: 2 · 2022: 3 · 2021: 4 · 2020: 3 · 2019: 9 · 2018: 6 · 2017: 5 · 2016: 6 · 2015: 9 · 2014: 13 · 2013: 8 · 2012: 4
- FWCI
- 7.74
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- SERVAL (Université de Lausanne) (acceptedVersion, other-oa)
- IRIS (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Figshare (submittedVersion, cc-by)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Sulfur Compounds in Biology
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- N-acetylcysteine, glutathione, schizophrenia, EEG synchronization, resting-state EEG, redox dysregulation, treatment biomarkers, neuronal connectivity
- MeSH terms
- Acetylcysteine, Adult, Double-Blind Method, Electroencephalography, Female, Glutathione, Humans, Male, Oscillometry, Oxidation-Reduction, Placebos, Schizophrenia, Signal Processing, Computer-Assisted, Models, Statistical, Biomarkers, Multivariate Analysis, Free Radical Scavengers, Cross-Over Studies
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