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Cited by 285Schizophrenia research and treatmentAntioxidant Activity and Oxidative StressTryptophan and brain disorders

Antioxidants, Redox Signaling, and Pathophysiology in Schizophrenia: An Integrative View

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Yao, Jeffrey K., Keshavan, Matcheri S.·2011·Antioxidants & Redox Signaling
DOI 10.1089/ars.2010.3603PMC PMC3159108
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Abstract

Schizophrenia (SZ) is a brain disorder that has been intensively studied for over a century; yet, its etiology and multifactorial pathophysiology remain a puzzle. However, significant advances have been made in identifying numerous abnormalities in key biochemical systems. One among these is the antioxidant defense system (AODS) and redox signaling. This review summarizes the findings to date in human studies. The evidence can be broadly clustered into three major themes: perturbations in AODS, relationships between AODS alterations and other systems ( i.e. , membrane structure, immune function, and neurotransmission), and clinical implications. These domains of AODS have been examined in samples from both the central nervous system and peripheral tissues. Findings in patients with SZ include decreased nonenzymatic antioxidants, increased lipid peroxides and nitric oxides, and homeostatic imbalance of purine catabolism. Reductions of plasma antioxidant capacity are seen in patients with chronic illness as well as early in the course of SZ. Notably, these data indicate that many AODS alterations are independent of treatment effects. Moreover, there is burgeoning evidence indicating a link among oxidative stress, membrane defects, immune dysfunction, and multineurotransmitter pathologies in SZ. Finally, the body of evidence reviewed herein provides a theoretical rationale for the development of novel treatment approaches. Antioxid. Redox Signal. 15, 2011–2035.

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  • Gclm KO mice represent a valid animal model, as low brain GSH levels and genetic association with GCLM have been reported in schizophrenia.

    “and represent a valid animal model, as low brain GSH levels (18,19) and genetic association with GCLM have been reported in schizophrenia (22).”

    From Perineuronal nets protect fast-spiking interneurons against oxidative stress (2013) · cites this paper as [19]

    The Introduction (page unavailable) reports reduced prefrontal brain GSH in schizophrenia and a genetic association involving the catalytic subunit of glutamate cysteine ligase. It does not establish an association with GCLM, the modifier subunit, or assess whether Gclm knockout mice are a valid animal model. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • Reduced antioxidant enzymes have been reported in patients with schizophrenia.

    “Reduced antioxidant enzymes are reported in schizophrenic patients (4–8)”

    From Prolonged Period of Cortical Plasticity upon Redox Dysregulation in Fast-Spiking Interneurons (2015) · cites this paper as [6]

  • Evidence for oxidative stress has been found in patients with schizophrenia, including increased lipid and protein oxidation in blood, CSF and post-mortem tissue, altered plasma antioxidants, and altered CSF superoxide dismutase-1 levels.

    “Evidence for oxidative stress has been found in patients with schizophrenia, including increased lipid and protein oxidation in blood, cerebrospinal fluid (CSF) and post-mortem tissue 36,37 , as well as altered levels of plasma antioxidants (such as vitamins C and E, catalase, GSH and GSH-peroxidase) 36,38 and CSF superoxide dismutase-1 levels 39 .”

    From Linking early-life NMDAR hypofunction and oxidative stress in schizophrenia pathogenesis (2016) · cites this paper as [38]

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Authors
Yao, J. K., & Keshavan, M. S.
Affiliations
  • University of Pittsburgh (US)
  • Beth Israel Deaconess Medical Center (US)
Corresponding author
Yao, Jeffrey K.
ORCID
Keshavan, Matcheri S.
Venue
Antioxidants & Redox Signaling
Publisher
SAGE Publications
Published
2011-10
Volume
15
Issue
7
Pages
2011-2035
ISSN
  • 1523-0864 (ISSN-L)
  • 1557-7716
DOI
10.1089/ars.2010.3603
PMC
PMC3159108
OpenAlex
W2063765492
Cited by
285
References
296
Citations by year
2026: 14 · 2025: 13 · 2024: 8 · 2023: 10 · 2022: 13 · 2021: 20 · 2020: 17 · 2019: 25 · 2018: 16 · 2017: 27 · 2016: 26 · 2015: 23 · 2014: 25 · 2013: 26 · 2012: 13
FWCI
2.15
Type
journal article
Language
en
Open access
Licence
journals.sagepub.com/page/policies/text-and-data-mining-license (tdm)
Locations
  • Antioxidants and Redox Signaling (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • U.S. Department of Veterans Affairs
  • Office of Research and Development (MH58141)
  • VA Pittsburgh Healthcare System
  • National Institute of Mental Health (MH-58141, R01MH045203, MH45203, R01MH058141)
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
  • Health Sciences › Medicine › Biochemistry › Antioxidant Activity and Oxidative Stress
  • Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
Keywords
schizophrenia, antioxidant defense, redox signaling, oxidative stress, lipid peroxidation, nitric oxide, purine catabolism, plasma antioxidant capacity, membrane structure, immune dysfunction, neurotransmission, schizophrenia pathophysiology, novel treatment approaches
MeSH terms
Animals, Antioxidants, Blood Proteins, Cell Membrane, Glutathione, Humans, Inflammation, Synaptic Transmission, Nitric Oxide, Oxidation-Reduction, Schizophrenia, Signal Transduction, Reactive Oxygen Species, Neurotransmitter Agents, Oxidative Stress, Lipid Metabolism

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