Redox dysregulation, neurodevelopment, and schizophrenia
Abstract
In schizophrenia, a developmental redox dysregulation constitutes one 'hub' on which converge genetic impairments of glutathione synthesis and environmental vulnerability factors generating oxidative stress. Their timing at critical periods of neurodevelopment could play a decisive role in inducing impairment of neural connectivity and synchronization as observed in schizophrenia. In experimental models, such redox dysregulation induces anomalies strikingly similar to those observed in patients. This is mediated by hypoactive NMDA receptors, impairment of fast-spiking parvalbumin GABA interneurons and deficit in myelination. A treatment restoring the redox balance without side effects yields improvements of negative symptoms in chronic patients. Novel interventions based on these mechanisms if applied in early phases of the disease hold great therapeutic promise.
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Redox dysregulation contributes to aberrant developmental trajectories in schizophrenia and early correction of this imbalance may have therapeutic potential.
“these studies seem to support the idea that redox dysregulation contributes to aberrant developmental trajectories in schizophrenia and that early correction of this imbalance may have therapeutic potential 86 .”
From Developmental timing and critical windows for the treatment of psychiatric disorders (2016) · cites this paper as [86]
The PV-cell-specific Gclc manipulation did not cause myelin deficits typically observed upon global redox dysregulation.
“The cell-specific manipulation was subtle and did not cause myelin deficits (Figure 1D,E) typically observed upon global redox dysregulation (3, 37).”
From Prolonged Period of Cortical Plasticity upon Redox Dysregulation in Fast-Spiking Interneurons (2015) · cites this paper as [3]
Redox dysregulation, an imbalance between oxidative stress and antioxidant defense, may contribute to schizophrenia pathogenesis.
“Mounting evidence also indicates that “redox dysregulation,” an imbalance between oxidative stress and antioxidant defense systems, may play a role in the pathogenesis (reviewed in ref. (3)).”
From Prolonged Period of Cortical Plasticity upon Redox Dysregulation in Fast-Spiking Interneurons (2015) · cites this paper as [3]
Mis-timed developmental trajectories of brain plasticity may contribute in part to the etiology of mental illnesses involving oxidative stress, such as schizophrenia.
“Mis-timed developmental trajectories of brain plasticity may therefore contribute in part to the etiology of mental illnesses involving oxidative stress, such as schizophrenia (2, 3, 18).”
From Prolonged Period of Cortical Plasticity upon Redox Dysregulation in Fast-Spiking Interneurons (2015) · cites this paper as [3]
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- Authors
- Do, K. Q., Cabungcal, J. H., Frank, A., Steullet, P., & Cuenod, M.
- Affiliations
- Centre Hospitalier Universitaire Vaudois (CH)
- Corresponding author
- Cabungcal, Jan H
- Frank, Anita
- Steullet, Pascal
- ORCID
- Steullet, Pascal
- Venue
- Current Opinion in Neurobiology
- Publisher
- Elsevier BV
- Published
- 2009-04
- Volume
- 19
- Issue
- 2
- Pages
- 220-230
- ISSN
- 0959-4388 (ISSN-L)
- OpenAlex
- W2043952421
- Cited by
- 384
- References
- 16
- Citations by year
- 2026: 12 · 2025: 19 · 2024: 8 · 2023: 19 · 2022: 19 · 2021: 23 · 2020: 15 · 2019: 24 · 2018: 22 · 2017: 17 · 2016: 30 · 2015: 25 · 2014: 29 · 2013: 38 · 2012: 34
- FWCI
- 3.45
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Current Opinion in Neurobiology (publishedVersion)
- PubMed (publishedVersion)
- IRIS (submittedVersion)
- SERVAL (Université de Lausanne) (submittedVersion)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Keywords
- schizophrenia, redox dysregulation, oxidative stress, glutathione synthesis, brain development, NMDA receptor hypofunction, parvalbumin interneurons, myelination, neuronal connectivity, negative symptoms, early intervention
- MeSH terms
- Animals, Brain, Glutathione, Humans, Models, Neurological, Oxidation-Reduction, Schizophrenia, Oxidative Stress
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