Oxidative stress in psychiatric disorders: evidence base and therapeutic implications

Ng, Felicity; Berk, Michael; Dean, Olivia; Bush, Ashley I.

doi:10.1017/s1461145707008401

Cited by 1,069Antioxidant Activity and Oxidative StressTryptophan and brain disordersRedox biology and oxidative stress

Oxidative stress in psychiatric disorders: evidence base and therapeutic implications

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Ng, Felicity, Berk, Michael, Dean, Olivia, Bush, Ashley I.·2008·The International Journal of Neuropsychopharmacology

DOI 10.1017/s1461145707008401

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Abstract

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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Stress related to psychopathology is associated with physiological and cellular alterations related to telomere length, such as elevated oxidative stress or inflammation.
“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]
Oxidative stress in psychiatric disorders could result from overproduction of ROS, impairments in Keap1-Nrf2 signalling, or both, due to psychological stress, physiological impairments, inflammation, and genetic polymorphisms of antioxidant enzymes.
“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]
Antioxidants have shown promising therapeutic benefits in the treatment of psychiatric disorders.
“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]
Increased oxidative damage occurs quite often in bipolar disorder.
“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]
NAC, which is a precursor of glutathione, can significantly improve the standard therapy, as a double-blind randomized placebo-controlled clinical study performed by Ng et al. in 2008 demonstrated.
“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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Reactive Oxygen Species, Toxicity, Oxidative Stress, and Antioxidants: Chronic Diseases and Aging
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A review of peripheral biomarkers in major depression: The potential of inflammatory and oxidative stress biomarkers
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Oxidative stress-related biomarkers in autism: Systematic review and meta-analyses
Frustaci, A., Neri, M., Cesario, A., Adams, J. B., Domenici, E., Bernardina, B. D., & Bonassi, S. (2012) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2012.03.011 · Cited by 370 · see citing works
Post stroke depression and risk of stroke recurrence and mortality: A systematic review and meta-analysis
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Oxidative stress in the skin: Impact and related protection
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Inflammation in Anxiety
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Association of Microvascular Dysfunction With Late-Life Depression
van Agtmaal, M. J. M., Houben, A. J. H. M., Pouwer, F., Stehouwer, C. D. A., & Schram, M. T. (2017) · JAMA Psychiatry · doi:10.1001/jamapsychiatry.2017.0984 · Cited by 313 · see citing works
The Association Between Habitual Diet Quality and the Common Mental Disorders in Community-Dwelling Adults
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Biomarkers and clinical staging in psychiatry
McGorry, P. D., Keshavan, M. S., Goldstone, S. D., Amminger, G. P., Allott, K., Berk, M., Lavoie, S., Pantelis, C., Yung, A. R., Wood, S. J., et al. (2014) · World Psychiatry · doi:10.1002/wps.20144 · Cited by 305 · see citing works
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Depression gets old fast: do stress and depression accelerate cell aging?
Wolkowitz, O. M., Epel, E. S., Reus, V. I., & Mellon, S. H. (2010) · Depression and Anxiety · doi:10.1002/da.20686 · Cited by 298 · see citing works
Nutritional modulation of cognitive function and mental health
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Dietary recommendations for the prevention of depression
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Delusional Infestation
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Superoxide Dismutase Administration: A Review of Proposed Human Uses
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Cytokines in bipolar disorder: A systematic review and meta-analysis
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Authors: Ng, F., Berk, M., Dean, O., & Bush, A. I.
Affiliations: Barwon Health (AU)
Mental Health Research Institute (AU)
ORCID: Ng, Felicity
Dean, Olivia
Bush, Ashley I.
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
DOI: 10.1017/s1461145707008401
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 › 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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Oxidative stress in psychiatric disorders: evidence base and therapeutic implications

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