Altered glutathione redox state in schizophrenia.
Open accessAbstract
Altered antioxidant status has been reported in schizophrenia. The glutathione (GSH) redox system is important for reducing oxidative stress. GSH, a radical scavenger, is converted to oxidized glutathione (GSSG) through glutathione peroxidase (GPx), and converted back to GSH by glutathione reductase (GR). Measurements of GSH, GSSG and its related enzymatic reactions are thus important for evaluating the redox and antioxidant status. In the present study, levels of GSH, GSSG, GPx and GR were assessed in the caudate region of postmortem brains from schizophrenic patients and control subjects (with and without other psychiatric disorders). Significantly lower levels of GSH, GPx, and GR were found in schizophrenic group than in control groups without any psychiatric disorders. Concomitantly, a decreased GSH:GSSG ratio was also found in schizophrenic group. Moreover, both GSSG and GR levels were significantly and inversely correlated to age of schizophrenic patients, but not control subjects. No significant differences were found in any GSH redox measures between control subjects and individuals with other types of psychiatric disorders. There were, however, positive correlations between GSH and GPx, GSH and GR, as well as GPx and GR levels in control subjects without psychiatric disorders. These positive correlations suggest a dynamic state is kept in check during the redox coupling under normal conditions. By contrast, lack of such correlations in schizophrenia point to a disturbance of redox coupling mechanisms in the antioxidant defense system, possibly resulting from a decreased level of GSH as well as age‐related decreases of GSSG and GR activities.
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Redox dysregulation has been observed in schizophrenic patients, who have defective antioxidant systems and exhibit increased lipid peroxidation.
“Redox dysregulation has been observed in schizophrenic patients, who have defective antioxidant systems and exhibit increased lipid peroxidation (Do et al., 2000; Yao et al., 2006; Flatow et al., 2013).”
From The Perineuronal ‘Safety’ Net? Perineuronal Net Abnormalities in Neurological Disorders (2018) · cites this paper as Yao et al., 2006
Higher levels of oxidative stress have been reported in schizophrenia.
“Higher levels of oxidative stress have been reported in schizophrenia (Wang et al, 2009;Yao et al, 2006)”
From Reduced Labeling of Parvalbumin Neurons and Perineuronal Nets in the Dorsolateral Prefrontal Cortex of Subjects with Schizophrenia (2016) · cites this paper as Yao et al, 2006
In an animal model with low glutathione content, as reported in the brain of some schizophrenia patients, there is a deficit in prefrontal and hippocampal parvalbumin interneurons, impairing high-frequency neuronal synchronization.
“In an animal model with low GSH content, as reported in the brain of some schizophrenia patients (Do et al., 2000; Gawryluk et al., 2011; Yao et al., 2006), there is a deficit in prefrontal and hippocampal PVI, impairing high-frequency neuronal synchronization (Cabungcal et al., 2013a; Cabungcal et al., 2013b; Steullet et al., 2010).”
From Redox dysregulation, neuroinflammation, and NMDA receptor hypofunction: A “central hub” in schizophrenia pathophysiology? (2016) · cites this paper as Yao et al., 2006
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- Authors
- Yao, J. K., Leonard, S., & Reddy, R.
- Affiliations
- University of Pittsburgh (US)
- Denver VA Medical Center (US)
- VA Pittsburgh Healthcare System (US)
- Corresponding author
- Yao, Jeffrey K.
- ORCID
- Reddy, Ravinder
- Venue
- Disease Markers
- Publisher
- Wiley
- Published
- 2006-01
- Volume
- 22
- Issue
- 1-2
- Pages
- 83-93
- ISSN
- 0278-0240 (ISSN-L)
- 1875-8630
- PMC
- PMC3850558
- OpenAlex
- W2088215062
- Cited by
- 321
- References
- 45
- Citations by year
- 2026: 11 · 2025: 9 · 2024: 6 · 2023: 10 · 2022: 20 · 2021: 20 · 2020: 10 · 2019: 16 · 2018: 19 · 2017: 18 · 2016: 18 · 2015: 21 · 2014: 12 · 2013: 18 · 2012: 21
- FWCI
- 6.18
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Disease Markers (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Mental Health (MH58141, MH64118, DA09457)
- Brain and Behavior Research Foundation
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Glutathione Transferases and Polymorphisms
- Health Sciences › Medicine › Biochemistry › Antioxidant Activity and Oxidative Stress
- Keywords
- schizophrenia, glutathione, glutathione disulfide, glutathione peroxidase, glutathione reductase, GSH/GSSG ratio, oxidative stress, antioxidant defense, redox coupling, caudate nucleus, postmortem brain, age-related decline
- MeSH terms
- Age Factors, Aged, Caudate Nucleus, Female, Glutathione, Glutathione Reductase, Humans, Male, Middle Aged, Oxidation-Reduction, Schizophrenia, Sex Factors, Smoking, Glutathione Disulfide
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