Cited by 169Bipolar Disorder and TreatmentAntioxidant Activity and Oxidative StressTreatment of Major Depression

Oxidative stress in early stage Bipolar Disorder and the association with response to lithium

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de Sousa, Rafael T., Zarate, Carlos A., Zanetti, Marcus V., Costa, Alana C., Talib, Leda L., Gattaz, Wagner F., Machado-Vieira, Rodrigo·2014·Journal of Psychiatric Research

Abstract

Background Several studies have described increased oxidative stress (OxS) parameters and imbalance of antioxidant enzymes in Bipolar Disorder (BD) but few is know about the impact of treatment at these targets. However, no study has evaluated OxS parameters in unmedicated early stage BD and their association with lithium treatment in bipolar depression.Methods Patients with BD I or II (n = 29) in a depressive episode were treated for 6 weeks with lithium. Plasma samples were collected at baseline and endpoint, and were also compared to age-matched controls (n = 28). The thiobarbituric acid reactive substances (TBARS), and the antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activities were measured.Results Subjects with BD depression at baseline presented a significant increase in CAT (p = 0.005) and GPx (p < 0.001) levels, with lower SOD/CAT ratio (p = 0.001) and no changes on SOD or TBARS compared to healthy controls. Regarding therapeutics, lithium only induced a decrease in TBARS (p = 0.023) and SOD (p = 0.029) levels, especially in BDII. Finally, TBARS levels were significantly lower at endpoint in lithium responders compared to non-responders (p = 0.018) with no difference in any biomarker regarding remission.Conclusion The present findings suggest a reactive increase in antioxidant enzymes levels during depressive episodes in early stage BD with minimal prior treatment. Also, decreased lipid peroxidation (TBARS) levels were observed, associated with lithium's clinical efficacy. Overall, these results reinforce the role for altered oxidative stress in the pathophysiology of BD and the presence of antioxidant effects of lithium in the prevention of illness progression and clinical efficacy.

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  1. Liochev SI Fridovich I The relative importance of HO* and ONOO– in mediating the toxicity of O*– Free Radic Biol Med 1999 26 777 8 10218668

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Authors
de Sousa, R. T., Zarate, C. A., Zanetti, M. V., Costa, A. C., Talib, L. L., Gattaz, W. F., & Machado-Vieira, R.
Affiliations
  • National Institutes of Health (US)
  • Universidade de São Paulo (BR)
Venue
Journal of Psychiatric Research
Publisher
Elsevier BV
Published
2014-03
Volume
50
Pages
36-41
ISSN
0022-3956 (ISSN-L)
OpenAlex
W2085273391
Cited by
169
References
69
Citations by year
2026: 4 · 2025: 10 · 2024: 15 · 2023: 9 · 2022: 10 · 2021: 16 · 2020: 19 · 2019: 12 · 2018: 11 · 2017: 10 · 2016: 22 · 2015: 15 · 2014: 15 · 2012: 1
FWCI
12.28
Type
journal article
Language
en
Open access
Locations
  • Journal of Psychiatric Research (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
Associação Beneficente Alzira Denise Hertzog da Silva (ABADHS)
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Bipolar Disorder and Treatment
  • Health Sciences › Medicine › Biochemistry › Antioxidant Activity and Oxidative Stress
  • Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
Keywords
bipolar disorder, oxidative stress, lithium, bipolar depression, lipid peroxidation, antioxidant enzymes, superoxide dismutase, catalase, glutathione peroxidase, treatment response, biomarkers
MeSH terms
Adult, Bipolar Disorder, Catalase, Depression, Female, Glutathione Peroxidase, Humans, Male, Superoxide Dismutase, Time Factors, Lithium Carbonate, Treatment Outcome, Thiobarbituric Acid Reactive Substances, Oxidative Stress, Antimanic Agents

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