Cited by 371Schizophrenia research and treatmentAmino Acid Enzymes and MetabolismTreatment of Major Depression

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Glutathione Precursor, N-Acetyl-Cysteine, Improves Mismatch Negativity in Schizophrenia Patients

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Lavoie, Suzie, Murray, Micah M, Deppen, Patricia, Knyazeva, Maria G, Berk, Michael, Boulat, Olivier, Bovet, Pierre, Bush, Ashley I, Conus, Philippe, Copolov, David, Fornari, Eleonora, Meuli, Reto, Solida, Alessandra, Vianin, Pascal, Cuénod, Michel, Buclin, Thierry, Do, Kim Q·2008·Neuropsychopharmacology

DOI 10.1038/sj.npp.1301624

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Abstract

In schizophrenia patients, glutathione dysregulation at the gene, protein and functional levels, leads to N-methyl-D-aspartate (NMDA) receptor hypofunction. These patients also exhibit deficits in auditory sensory processing that manifests as impaired mismatch negativity (MMN), which is an auditory evoked potential (AEP) component related to NMDA receptor function. N-acetyl-cysteine (NAC), a glutathione precursor, was administered to patients to determine whether increased levels of brain glutathione would improve MMN and by extension NMDA function. A randomized, double-blind, cross-over protocol was conducted, entailing the administration of NAC (2 g/day) for 60 days and then placebo for another 60 days (or vice versa). 128-channel AEPs were recorded during a frequency oddball discrimination task at protocol onset, at the point of cross-over, and at the end of the study. At the onset of the protocol, the MMN of patients was significantly impaired compared to sex- and age- matched healthy controls (p=0.003), without any evidence of concomitant P300 component deficits. Treatment with NAC significantly improved MMN generation compared with placebo (p=0.025) without any measurable effects on the P300 component. MMN improvement was observed in the absence of robust changes in assessments of clinical severity, though the latter was observed in a larger and more prolonged clinical study. This pattern suggests that MMN enhancement may precede changes to indices of clinical severity, highlighting the possible utility AEPs as a biomarker of treatment efficacy. The improvement of this functional marker may indicate an important pathway towards new therapeutic strategies that target glutathione dysregulation in schizophrenia.

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Authors: Lavoie, S., Murray, M. M., Deppen, P., Knyazeva, M. G., Berk, M., Boulat, O., Bovet, P., Bush, A. I., Conus, P., Copolov, D., Fornari, E., Meuli, R., Solida, A., Vianin, P., Cuénod, M., Buclin, T., & Do, K. Q.
Affiliations: Centre Hospitalier Universitaire Vaudois (CH)
Mental Health Research Institute (AU)
Monash University (AU)
ORCID: Lavoie, Suzie
Murray, Micah M
Knyazeva, Maria G
Bush, Ashley I
Conus, Philippe
Copolov, David
Fornari, Eleonora
Meuli, Reto
Solida, Alessandra
Cuénod, Michel
Buclin, Thierry
Venue: Neuropsychopharmacology
Publisher: Springer Science and Business Media LLC
Published: 2007-11-14
Volume: 33
Issue: 9
Pages: 2187-2199
ISSN: 0893-133X (ISSN-L)
1740-634X
DOI: 10.1038/sj.npp.1301624
OpenAlex: W2003906510
Cited by: 371
References: 67
Citations by year: 2026: 7 · 2025: 11 · 2024: 4 · 2023: 15 · 2022: 10 · 2021: 22 · 2020: 21 · 2019: 33 · 2018: 16 · 2017: 27 · 2016: 19 · 2015: 28 · 2014: 31 · 2013: 23 · 2012: 28
FWCI: 11.05
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.springer.com/tdm (tdm)
Locations: Neuropsychopharmacology (publishedVersion)
PubMed (publishedVersion)
Own your potential (DEAKIN) (submittedVersion)
Figshare (submittedVersion, cc-by)
IRIS (submittedVersion)
Minerva Access (University of Melbourne) (submittedVersion)
SERVAL (Université de Lausanne) (submittedVersion)
Funders: Stanley Medical Research Institute
Centre d'Imagerie BioMédicale
Topics: Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
Keywords: N-acetylcysteine, glutathione, schizophrenia, mismatch negativity, NMDA receptor hypofunction, auditory evoked potentials, P300, auditory sensory processing, glutathione precursor
MeSH terms: Acetylcysteine, Acoustic Stimulation, Adult, Brain Mapping, Cerebral Cortex, Contingent Negative Variation, Discrimination, Psychological, Double-Blind Method, Electroencephalography, Evoked Potentials, Auditory, Female, Glutathione, Humans, Male, Middle Aged, Neuropsychological Tests, Reaction Time, Retrospective Studies, Schizophrenia, Time Factors, Free Radical Scavengers, Cross-Over Studies

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Glutathione Precursor, N-Acetyl-Cysteine, Improves Mismatch Negativity in Schizophrenia Patients

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