ArticleAntioxidants (Basel, Switzerland)2021
Counteracting Effects of Glutathione on the Glutamate-Driven Excitation/Inhibition Imbalance in First-Episode Schizophrenia: A 7T MRS and Dynamic Causal Modeling Study.
Article in Antioxidants (Basel, Switzerland), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 39 citations in OpenAlex.
- Glutathione in Our Diet and Its Role in the Body: From Disease Prevention to Anti-Aging.Nutrients · 2026Review
- Association of GRM7 Polymorphisms with Bilateral Auditory Regions Glutamate and Coupling with Glutathione in ARHL Patients.Molecular neurobiology · 2025Article
- Inhibition of oxidative stress, neuroinflammatory cytokines, and protein expressions contributes to the antipsychotic effects of geraniol in mice with ketamine-induced schizophrenia.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2025Article
- Intranasal Insulin Increases Brain Glutathione and Enhances Antioxidant Capacity in Healthy Participants but Not in Those With Early Psychotic Disorders.Biological psychiatry. Cognitive neuroscience and neuroimaging · 2025Article
- Leveraging ultra-high field (7T) MRI in psychiatric research.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2024Review
- The Impacts of Adolescent Cannabinoid Exposure on Striatal Anxiety- and Depressive-Like Pathophysiology Are Prevented by the AntioxidantBiological psychiatry global open science · 2024Article
- The impact of spectral basis set composition on estimated levels of cingulate glutamate and its associations with different personality traits.BMC psychiatry · 2024Article
- Glutamatergic basis of antipsychotic response in first-episode psychosis: a dual voxel study of the anterior cingulate cortex.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2024Article
- Schizophrenia Synaptic Pathology and Antipsychotic Treatment in the Framework of Oxidative and Mitochondrial Dysfunction: Translational Highlights for the Clinics and Treatment.Antioxidants (Basel, Switzerland) · 2023Review
- Multinuclear Magnetic Resonance Spectroscopy at Ultra-High-Field: Assessing Human Cerebral Metabolism in Healthy and Diseased States.Metabolites · 2023Review
- A Mitochondrial Perspective on Noncommunicable Diseases.Biomedicines · 2023Review
- Oxidative Stress and Emergence of Psychosis.Antioxidants (Basel, Switzerland) · 2022Review
- Microstructural imaging and transcriptomics of the basal forebrain in first-episode psychosis.Translational psychiatry · 2022Article
- Sex-Specific Association between Antioxidant Defense System and Therapeutic Response to Risperidone in Schizophrenia: A Prospective Longitudinal Study.Current neuropharmacology · 2022Article
- Ultra-high field neuroimaging in psychosis: A narrative review.Frontiers in psychiatry · 2022Review
- Is There a Glutathione Centered Redox Dysregulation Subtype of Schizophrenia?Antioxidants (Basel, Switzerland) · 2021Review
- Pro/Antioxidant State as a Potential Biomarker of Schizophrenia.Journal of clinical medicine · 2021Article
- Neural Correlates of Aberrant Salience and Source Monitoring in Schizophrenia and At-Risk Mental States-A Systematic Review of fMRI Studies.Journal of clinical medicine · 2021Review
- Glutathione as a Molecular Marker of Functional Impairment in Patients with At-Risk Mental State: 7-TeslaBrain sciences · 2021Article
- Acute conceptual disorganization in untreated first-episode psychosis: a combined magnetic resonance spectroscopy and diffusion imaging study of the cingulum.Journal of psychiatry & neuroscience : JPN · 2021Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Oxidative stress plays a key role in the pathophysiology of schizophrenia. While free radicals produced by glutamatergic excess and oxidative metabolism have damaging effects on brain tissue, antioxidants such as glutathione (GSH) counteract these effects. The interaction between glutamate (GLU) and GSH is centered on N-Methyl-D-aspartate (NMDA) receptors. GSH levels increase during glutamate-mediated excitatory neuronal activity, which serves as a checkpoint to protect neurons from oxidative damage and reduce excitatory overdrive. We studied the possible influence of GSH on the glutamate-mediated dysconnectivity in 19 first-episode schizophrenia (FES) patients and 20 healthy control (HC) subjects. Using ultra-high field (7 Tesla) magnetic resonance spectroscopy (MRS) and resting state functional magnetic resonance imaging (fMRI), we measured GSH and GLU levels in the dorsal anterior cingulate cortex (dACC) and blood-oxygenation level-dependent activity in both the dACC and the anterior insula (AI). Using spectral dynamic causal modeling, we found that when compared to HCs, in FES patients inhibitory activity within the dACC decreased with GLU levels whereas inhibitory activity in both the dACC and AI increased with GSH levels. Our model explains how higher levels of GSH can reverse the downstream pathophysiological effects of a hyperglutamatergic state in FES. This provides an initial insight into the possible mechanistic effect of antioxidant system on the excitatory overdrive in the salience network (dACC-AI).
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.