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Oxidative stress in psychiatric disorders: evidence base and therapeutic implications
Open accessAbstract
Oxidative stress has been implicated in the pathogenesis of diverse disease states, and may be a common pathogenic mechanism underlying many major psychiatric disorders, as the brain has comparatively greater vulnerability to oxidative damage. This review aims to examine the current evidence for the role of oxidative stress in psychiatric disorders, and its academic and clinical implications. A literature search was conducted using the Medline, Pubmed, PsycINFO, CINAHL PLUS, BIOSIS Preview, and Cochrane databases, with a time-frame extending to September 2007. The broadest data for oxidative stress mechanisms have been derived from studies conducted in schizophrenia, where evidence is available from different areas of oxidative research, including oxidative marker assays, psychopharmacology studies, and clinical trials of antioxidants. For bipolar disorder and depression, a solid foundation for oxidative stress hypotheses has been provided by biochemical, genetic, pharmacological, preclinical therapeutic studies and one clinical trial. Oxidative pathophysiology in anxiety disorders is strongly supported by animal models, and also by human biochemical data. Pilot studies have suggested efficacy of N-acetylcysteine in cocaine dependence, while early evidence is accumulating for oxidative mechanisms in autism and attention deficit hyperactivity disorder. In conclusion, multi-dimensional data support the role of oxidative stress in diverse psychiatric disorders. These data not only suggest that oxidative mechanisms may form unifying common pathogenic pathways in psychiatric disorders, but also introduce new targets for the development of therapeutic interventions.
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“This model is consistent with the idea that stress related to psychopathology is associated with physiological and cellular alterations related to telomere length, such as elevated oxidative stress or inflammation.25”
From Telomere Length and Psychopathology: Specificity and Direction of Effects Within the Bucharest Early Intervention Project (2020) · cites this paper as [25]
Experimental — accuracy not yet measuredIn the citing paper
“Oxidative stress in psychiatric disorders could result from the overproduction of ROS, impairments in Keap1-Nrf2 signalling, or both due to causes related to psychological stress, physiological impairments, inflammation, and genetic polymorphisms of antioxidant enzymes that are beyond the scope of this review [126,127].”
From Nrf2 and Oxidative Stress: A General Overview of Mechanisms and Implications in Human Disease (2022) · cites this paper as [126]
In the citing paper
“Importantly, antioxidants have shown promising therapeutic benefits in the treatment of psychiatric disorders and are subject to further investigation [126,127,140].”
From Nrf2 and Oxidative Stress: A General Overview of Mechanisms and Implications in Human Disease (2022) · cites this paper as [126]
In the citing paper
“bipolar disorder (BD) [10–14]”
From Oxidative Stress Implications in the Affective Disorders: Main Biomarkers, Animal Models Relevance, Genetic Perspectives, and Antioxidant Approaches (2016) · cites this paper as [13]
In the citing paper
“Coming back to NAC, which is a precursor of glutathione, it has been shown that it can significantly improve the standard therapy, as a double-blind randomized placebo-controlled clinical study performed by Ng et al. in 2008 demonstrated [13].”
From Oxidative Stress Implications in the Affective Disorders: Main Biomarkers, Animal Models Relevance, Genetic Perspectives, and Antioxidant Approaches (2016) · cites this paper as [13]
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Metadata
- Authors
- Ng, F., Berk, M., Dean, O., & Bush, A. I.
- Affiliations
- Barwon Health (AU)
- Mental Health Research Institute (AU)
- Venue
- The International Journal of Neuropsychopharmacology
- Publisher
- Oxford University Press (OUP)
- Published
- 2008-01-21
- Volume
- 11
- Issue
- 06
- Pages
- 851-76
- ISSN
- 1461-1457 (ISSN-L)
- 1469-5111
- OpenAlex
- W1986211748
- Cited by
- 1,069
- References
- 203
- Citations by year
- 2026: 23 · 2025: 52 · 2024: 49 · 2023: 60 · 2022: 52 · 2021: 81 · 2020: 73 · 2019: 69 · 2018: 74 · 2017: 42 · 2016: 84 · 2015: 71 · 2014: 74 · 2013: 68 · 2012: 50
- FWCI
- 4.26
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The International Journal of Neuropsychopharmacology (publishedVersion)
- PubMed (publishedVersion)
- Adelaide Research & Scholarship (AR&S) (University of Adelaide) (submittedVersion)
- Deakin Research Online (Deakin University) (submittedVersion)
- Figshare (submittedVersion, cc-by)
- Topics
- Health Sciences › Medicine › Biochemistry (medical) › Antioxidant Activity and Oxidative Stress
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Keywords
- oxidative stress, mental illness, schizophrenia, bipolar disorder, depression, anxiety disorders, cocaine dependence, autism spectrum disorder, attention deficit hyperactivity disorder, antioxidants, N-acetylcysteine, oxidative stress biomarkers, psychopharmacology, common pathogenic mechanisms
- MeSH terms
- Antioxidants, Mental Disorders, Humans, Databases, Bibliographic, Oxidative Stress
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