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Glutathione precursor N-acetyl-cysteine modulates EEG synchronization in schizophrenia patients: a double-blind, randomized, placebo-controlled trial.

Carmeli C, Knyazeva MG, Cuénod M, Do KQ - PLoS ONE (2012)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Center for Psychiatric Neuroscience, Department of Psychiatry, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Lausanne, Switzerland.

ABSTRACT

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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Related in: MedlinePlus

Surface topography of correlations between MPS and Liddle's factor of disorganization for NAC vs. Placebo contrast.Significant Pearson correlations at FDR<0.05 are shown in the alpha (α) and beta (β) frequency bands for CAR EEG and Laplacian data. Blue circles designate the sensors with inverse correlations. The size of the correlations is reported as the coefficient of determination defined as the square of the Pearson correlation value (R2).
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pone-0029341-g004: Surface topography of correlations between MPS and Liddle's factor of disorganization for NAC vs. Placebo contrast.Significant Pearson correlations at FDR<0.05 are shown in the alpha (α) and beta (β) frequency bands for CAR EEG and Laplacian data. Blue circles designate the sensors with inverse correlations. The size of the correlations is reported as the coefficient of determination defined as the square of the Pearson correlation value (R2).

Mentions: A correlation analysis allowed us to look at the relationship between EEG synchronization and the psychopathological scores of the patients. No correlations were found between MPS and PANSS scores for the contrast NAC vs. Placebo. Since various factor analytic studies point to the fact that three syndromes (negative, positive, and disorganization) may underlie schizophrenia symptomatology [48], [49], and that the disorganization syndrome is associated with executive functions and attention [50], [51], we also explored the relationship between EEG synchronization and Liddle's scores [30]. We found significant inverse correlations between Liddle's factor of disorganization and MPS changes in the NAC vs. Placebo contrast for the left parieto-temporal cluster at beta and gamma frequencies (Fig. 4). These correlations show that the greater the MPS increase, the greater the clinical improvement. The average value of the coefficient of determination (R2) was 0.39 for CAR EEG and 0.31 for Laplacian, which means that synchronization variation can predict or explain 39% and 31% of Liddle's score variation, respectively.


Glutathione precursor N-acetyl-cysteine modulates EEG synchronization in schizophrenia patients: a double-blind, randomized, placebo-controlled trial.

Carmeli C, Knyazeva MG, Cuénod M, Do KQ - PLoS ONE (2012)

Surface topography of correlations between MPS and Liddle's factor of disorganization for NAC vs. Placebo contrast.Significant Pearson correlations at FDR<0.05 are shown in the alpha (α) and beta (β) frequency bands for CAR EEG and Laplacian data. Blue circles designate the sensors with inverse correlations. The size of the correlations is reported as the coefficient of determination defined as the square of the Pearson correlation value (R2).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3285150&req=5

pone-0029341-g004: Surface topography of correlations between MPS and Liddle's factor of disorganization for NAC vs. Placebo contrast.Significant Pearson correlations at FDR<0.05 are shown in the alpha (α) and beta (β) frequency bands for CAR EEG and Laplacian data. Blue circles designate the sensors with inverse correlations. The size of the correlations is reported as the coefficient of determination defined as the square of the Pearson correlation value (R2).
Mentions: A correlation analysis allowed us to look at the relationship between EEG synchronization and the psychopathological scores of the patients. No correlations were found between MPS and PANSS scores for the contrast NAC vs. Placebo. Since various factor analytic studies point to the fact that three syndromes (negative, positive, and disorganization) may underlie schizophrenia symptomatology [48], [49], and that the disorganization syndrome is associated with executive functions and attention [50], [51], we also explored the relationship between EEG synchronization and Liddle's scores [30]. We found significant inverse correlations between Liddle's factor of disorganization and MPS changes in the NAC vs. Placebo contrast for the left parieto-temporal cluster at beta and gamma frequencies (Fig. 4). These correlations show that the greater the MPS increase, the greater the clinical improvement. The average value of the coefficient of determination (R2) was 0.39 for CAR EEG and 0.31 for Laplacian, which means that synchronization variation can predict or explain 39% and 31% of Liddle's score variation, respectively.

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Center for Psychiatric Neuroscience, Department of Psychiatry, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Lausanne, Switzerland.

ABSTRACT

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.

Show MeSH
Related in: MedlinePlus