3-Nitrotyrosine and glutathione antioxidant system in patients in the early and late stages of bipolar disorder

3-Nitrotyrosine and glutathione antioxidant system in patients in the early and late stages of bipolar disorder

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J Psychiatry Neurosci 2010; 34(4): 258-266

Ana Cristina Andreazza, Pharm D, PhD; Flavio Kapczinski, MD, PhD;
Marcia Kauer-Sant’Anna, MD, PhD; Julio C. Walz, PhD; David J. Bond, MD; Carlos A. Gonçalves, MD, PhD; L. Trevor Young, MD, PhD; Lakshmi N. Yatham, MBBS

Andreazza, Kauer-Sant’Anna, Bond, Young, Yatham — Department of Psychiatry, University of British Columbia, Vancouver, BC; Andreazza, Gonçalves — Departamento de Bioquímica, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul; Kapczinski, Kauer-Sant’Anna, Walz — Laboratório de Psiquiatria Molecular, Centro de Pesquisas, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil

Abstract

Background: There has been an increasing interest in the role of oxidative stress in the pathophysiology of bipolar disorder. To explore this further, we evaluated the activity of glutathione peroxidase (GPx), glutathione reductase (GR) and glutathione S-transferase (GST), as well as 3-nitrotyrosine levels and carbonyl content in patients in the early (within 3 years of illness onset) and late (a minimum of 10 years of illness) stages of bipolar disorder.

Methods: We matched 30 patients in the early stage and 30 patients in the late stage of bipolar disorder, diagnosed according to DSM-IV criteria, with 60 healthy controls (30 matched for each group of patients). We measured symptomatic status using the Hamilton Rating Scale for Depression and the Young Mania Rating Scale.

Results: We found a significant increase in 3-nitrotyrosine levels among patients in the early (p < 0.010) and late (p < 0.010) stages of bipolar disorder. The activity of GR and GST was increased only among patients in the late stage of illness. Glutathione peroxidase activity and carbonyl content did not differ among the groups.

Limitations: Limitations of our study include its cross-sectional design, which did not allow us to examine direct causative mechanisms or the effects of progression of illness, and the potential environmental bias introduced by comparing patient groups recruited from different regions of the world.

Conclusions: Our data indicate a possible tyrosine nitration-induced damage in patients with bipolar disorder that is present from the early stage of illness. Our data also indicate that patients in the late stage of illness demonstrate enhanced activity of GR and GST, which could suggest the involvement of a compensatory system in bipolar disorder.


Submitted Apr. 15, 2008; Revised Nov. 13, 2008, Feb. 9, 2009; Accepted Feb. 13, 2009

Competing interests: None declared for Drs. Andreazza, Walz and Gonçalves. Dr. Kapczinski has received speaker fees, educational grants and travel assistance from Eli Lilly. Dr. Kauer-Sant’Anna has been an investigator in clinical trials sponsored by Servier, Canadian Institutes of Health Research and Stanley Medical Research Institute. She is also a NARSAD Young Investigator and has received speaker fees or unrestricted research grants from APA/AstraZeneca, Lilly, CNPq and CAPES. Dr. Yatham has received speaker fees, educational grants and travel assistance from AstraZeneca and Eli Lilly. Dr. Bond has received speaker fees from AstraZeneca and CANMAT and sits on the advisory board of AstraZeneca. Dr. Young has received speaker fees from AstraZeneca and Eli Lilly.

Contributors: Drs. Andreazza, Kapczinski, Gonçalves, Young and Yatham designed the study. Drs. Andreazza, Walz, Bond and Yatham acquired the data, which Drs. Andreazza, Kapczinski, Kauer-Sant’Anna, Walz, Bond, Gonçalves and Yatham analyzed. Drs. Andreazza, Kapczinski, Kauer-Sant’Anna, Walz, Gonçalves and Young wrote the article, which Drs. Kapczinski, Kauer-Sant’Anna, Bond, Gonçalvez Young and Yatham reviewed. All authors approved the final version for publication.

Correspondence to: Dr. L.N. Yatham, Research and International Affairs, Department of Psychiatry, University of British Columbia, 2255 Wesbrook Mall, Vancouver BC V6T 2A1; fax 604 822-7922; yatham@interchange.ubc.ca