33
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Glutathione Precursor N-Acetyl-Cysteine Modulates EEG Synchronization in Schizophrenia Patients: A Double-Blind, Randomized, Placebo-Controlled Trial

      research-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          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.

          Trial Registration

          ClinicalTrials.gov NCT01506765

          Related collections

          Most cited references76

          • Record: found
          • Abstract: not found
          • Article: not found

          Controlling the False Discovery Rate: A Practical and Powerful Approach to Multiple Testing

            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Abnormal neural oscillations and synchrony in schizophrenia.

            Converging evidence from electrophysiological, physiological and anatomical studies suggests that abnormalities in the synchronized oscillatory activity of neurons may have a central role in the pathophysiology of schizophrenia. Neural oscillations are a fundamental mechanism for the establishment of precise temporal relationships between neuronal responses that are in turn relevant for memory, perception and consciousness. In patients with schizophrenia, the synchronization of beta- and gamma-band activity is abnormal, suggesting a crucial role for dysfunctional oscillations in the generation of the cognitive deficits and other symptoms of the disorder. Dysfunctional oscillations may arise owing to anomalies in the brain's rhythm-generating networks of GABA (gamma-aminobutyric acid) interneurons and in cortico-cortical connections.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Synaptic mechanisms of synchronized gamma oscillations in inhibitory interneuron networks.

              Gamma frequency oscillations are thought to provide a temporal structure for information processing in the brain. They contribute to cognitive functions, such as memory formation and sensory processing, and are disturbed in some psychiatric disorders. Fast-spiking, parvalbumin-expressing, soma-inhibiting interneurons have a key role in the generation of these oscillations. Experimental analysis in the hippocampus and the neocortex reveals that synapses among these interneurons are highly specialized. Computational analysis further suggests that synaptic specialization turns interneuron networks into robust gamma frequency oscillators.
                Bookmark

                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2012
                22 February 2012
                : 7
                : 2
                : e29341
                Affiliations
                [1 ]Center for Psychiatric Neuroscience, Department of Psychiatry, Centre Hospitalier Universitaire Vaudois (CHUV), University of Lausanne, Lausanne, Switzerland
                [2 ]Laboratoire de Recherche en Neuroimagerie (LREN), Département des Neurosciences Cliniques (DNC), Centre Hospitalier Universitaire Vaudois (CHUV), University of Lausanne, Lausanne, Switzerland
                [3 ]Department of Radiology, Centre Hospitalier Universitaire Vaudois (CHUV), University of Lausanne, Lausanne, Switzerland
                University of Queensland, Australia
                Author notes

                Conceived and designed the experiments: MC KD. Performed the experiments: MK. Analyzed the data: CC MK. Contributed reagents/materials/analysis tools: KD CC. Wrote the paper: CC MK KD.

                Article
                PONE-D-11-16113
                10.1371/journal.pone.0029341
                3285150
                22383949
                853a9b28-d070-400a-b380-196798f2ae3a
                Carmeli et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
                History
                : 8 August 2011
                : 25 November 2011
                Page count
                Pages: 9
                Categories
                Research Article
                Biology
                Biochemistry
                Neurochemistry
                Molecular Cell Biology
                Signal Transduction
                Signaling in Cellular Processes
                Neuroscience
                Neurochemistry
                Medicine
                Clinical Research Design
                Diagnostic Medicine
                Clinical Neurophysiology
                Drugs and Devices
                Mental Health
                Psychiatry
                Psychology
                Neurology
                Social and Behavioral Sciences
                Psychology

                Uncategorized
                Uncategorized

                Comments

                Comment on this article