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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
Glutathione precursor, N-acetyl-cysteine, improves mismatch negativity in schizophrenia patients
Neuropsychopharmacology, Volume 33, No. 9, Year 2008
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Description
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 (2g/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. © 2008 Nature Publishing Group All rights reserved.
Authors & Co-Authors
Berk, Michael
Australia, Melbourne
The Florey
Australia, Melbourne
University of Melbourne
Conus, Philippe O.
Switzerland, Lausanne
Université de Lausanne Unil
Solida, Alessandra
Switzerland, Lausanne
Université de Lausanne Unil
Buclin, Thierry J.
Switzerland, Lausanne
Université de Lausanne Unil
Statistics
Citations: 304
Authors: 4
Affiliations: 5
Identifiers
Doi:
10.1038/sj.npp.1301624
ISSN:
0893133X
Research Areas
Disability
Genetics And Genomics
Mental Health