Oxidative stress markers in bipolar disorder: a meta-analysis. J Affect Disord

Department of Psychiatry, University of British Columbia, Vancouver, BC, Canada.
Journal of Affective Disorders (Impact Factor: 3.38). 07/2008; 111(2-3):135-44. DOI: 10.1016/j.jad.2008.04.013
Source: PubMed


Oxidative stress is thought to mediate neuropathological processes of a number of neuropsychiatric disorders and recent data suggest that oxidative stress may be involved in the pathophysiology of bipolar disorder (BD). In the present investigation, we conducted a meta-analysis of studies that evaluated markers of oxidative stress in individuals with BD, as compared to healthy controls.
A Medline search was conducted to identify studies that measured peripheral markers of oxidative stress in bipolar disorder. Data were subjected to meta-analysis using a random effects model to examine the effect sizes of the pooled results. Bias assessment (Egger's test) and assessment of heterogeneity (I(2)) were also carried out.
Thiobarbituric acidic reactive substances (TBARS) (p = 0.001) as well as NO activity (p = 0.02) were significantly increased in BD with a large effect size for TBARS and a moderate effect size for increase in NO. No significant effect sizes were observed for the antioxidant enzymes superoxide dismutase, catalase and glutathione peroxidase (all p>0.05).
Some caution is warranted in interpreting these results: (1) Egger's test was positive for SOD, suggesting that SOD results may have been influenced by a publication bias. (2) We analyzed the absolute values of each antioxidant enzyme separately and the literature suggests that an imbalance between the antioxidant enzymes is a better indication of the presence of oxidative stress.
The present meta-analysis suggests that oxidative stress markers are increased in BD and that oxidative stress may play a role in the pathophysiology of BD.

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    • "Candesartan and lithium prevent and reverse AMPH-induced alterations in oxidative stress parameters Since pro-oxidative alterations are observed in BD patients (Andreazza et al., 2008) and also in animal models of mania (Macêdo et al., 2013), we evaluated the levels of the main endogenous antioxidant, GSH and lipid peroxidation in the hippocampus and cerebellar vermis. In the evaluation of hippocampal levels of GSH in the prevention protocol (Fig. 4A) we observed a significant interaction between lithium  AMPH [F (1, 25)=5.954, "
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    ABSTRACT: Activation of the brain angiotensin II type 1 receptor (AT1R) triggers pro-oxidant and pro-inflammatory mechanisms which are involved in the neurobiology of bipolar disorder (BD). Candesartan (CDS) is an AT1 receptor antagonist with potential neuroprotective properties. Herein we investigated CDS effects against oxidative, neurotrophic inflammatory and cognitive effects of amphetamine (AMPH)-induced mania. In the reversal protocol adult mice were given AMPH 2mg/kg i.p. or saline and between days 8 and 14 received CDS 0.1, 0.3 or 1mg/kg orally, lithium (Li) 47.5mg/kg i.p., or saline. In the prevention treatment, mice were pretreated with CDS, Li or saline prior to AMPH. Locomotor activity and working memory performance were assessed. Glutathione (GSH), thiobarbituric acid-reactive substance (TBARS) and TNF-α levels were evaluated in the hippocampus (HC) and cerebellar vermis (CV). Brain-derived neurotrophic factor (BDNF) and glycogen synthase kinase 3-beta (GSK-3beta) levels were measured in the HC. CDS and Li prevented and reversed the AMPH-induced increases in locomotor activity. Only CDS prevented and reversed AMPH-induced working memory deficits. CDS prevented AMPH-induced alterations in GSH (HC and CV), TBARS (HC and CV), TNF-α (HC and CV) and BDNF (HC) levels. Li prevented alterations in BDNF and phospho-Ser9-GSK3beta. CDS reversed AMPH-induced alterations in GSH (HC and CV), TBARS (HC), TNF-α (CV) and BDNF levels. Li reversed AMPH-induced alterations in TNF-α (HC and CV) and BDNF (HC) levels. CDS is effective in reversing and preventing AMPH-induced behavioral and biochemical alterations, providing a rationale for the design of clinical trials investigating CDS׳s possible therapeutic effects. Copyright © 2015 Elsevier B.V. and ECNP. All rights reserved.
    European neuropsychopharmacology: the journal of the European College of Neuropsychopharmacology 08/2015; 25(11). DOI:10.1016/j.euroneuro.2015.08.005 · 4.37 Impact Factor
    • "While age may play a factor, adults with BD show significantly elevated levels of oxidative stress compared to age-matched healthy controls, and it is expected that disease state and trait play a significant role in the observed peripheral oxidative stress marker levels [6] [31]. Furthermore, while these findings may represent an earlier stage of BD, in which the oxidant–antioxidant system has not yet been overwhelmed and oxidative stress factor levels are still considerably low [6] [10], it is worth underscoring that the mean duration of BD in our sample was longer than in previous early-stage adult BD findings. This suggests that both age and illness duration contribute to oxidative stress disturbance. "
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    ABSTRACT: In the field of bipolar disorder (BD) research there is an absence of validated biomarkers and limited understanding of the biology underlying excessive and premature cardiovascular disease (CVD). Oxidative stress is a potential biomarker in both BD and CVD. To examine psychiatric and cardiovascular characteristics associated with peripheral oxidative stress markers among adolescents with BD, who are at high risk for CVD. Participants were 30 adolescents, 13-19years old, with BD and without CVD. Ultrasonography was used to evaluate vascular function and structure. Traditional CVD risk factors were also measured. Psychiatric assessments were conducted via semi-structured interview. Serum levels of oxidative stress (lipid hydroperoxides (LPH) and protein carbonylation (PC)) were assayed. Compared to published data on adults with BD, adolescents had significantly lower levels of LPH and PC (t52(11.34), p<0.0001; t58(29.68), p<0.0001, respectively). Thicker mean and maximum carotid intima media thickness was associated with greater levels of LPH (r=.455, p=.015; r=.620, p<0.0001, respectively). LPH was associated with diastolic blood pressure (r=-.488, p=0.008) and pulse pressure (r=.543, p=0.003). Mood symptoms and medication were not significantly associated with oxidative stress. Adolescents with BD have lower levels of oxidative stress compared to adults with BD, supporting prevailing illness staging theories for BD. Oxidative stress is robustly associated with a proxy measure of atherosclerosis and may explain in part the increased risk of CVD in BD. Copyright © 2015 Elsevier Inc. All rights reserved.
    Journal of psychosomatic research 04/2015; 79(3). DOI:10.1016/j.jpsychores.2015.04.005 · 2.74 Impact Factor
    • "González-Estecha et al.[22] finding of increased blood and urine levels of lead and cadmium in bipolar disorder may reflect a high past lead exposure in childhood and adolescence. These increased blood lead levels also indicate that oxidative stress may play a role in the pathophysiology of bipolar disorder, as suggested by a meta-analysis showing that oxidative stress markers are increased in bipolar disorder[35]. In the NHANES 1999-2004 study, persons with blood lead levels in the highest quintile (≥2.1 μg/dL) had a 2.3-fold increased risk of meeting DSM-IV criteria for major depression disorder and a 4.9-fold increased risk of panic disorder as those in the lowest quintile (0.7 μg/dL)[21]. "
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    ABSTRACT: Psychiatric disorders are associated with long-term disability and huge social and economic costs. The possible influence of heavy metals exposure on public health remains a matter of concern. A recurring research question that persisted among researchers in neuropsychiatry has been "are psychiatric patients more likely to have a high body burden of lead or other heavy metals?" This is an update account on the role of lead and cadmium in psychiatry. This review, which has employed search words like "lead and cadmium in psychiatry", "lead and cadmium in schizophrenia", "lead and cadmium in psychosis" in citation indices such as PubMed, Google Scholar, Scirus, and Scopus. A total of 415 articles were found; 60 fulfiled the inclusion criteria. Evidence-based information suggests that lead and cadmium may be involved in psychiatry. Should environmental lead and cadmium be implicated in the etiogenesis of psychiatry given the characteristic high environmental pollution in Sub Sahara Africa, it is worthwhile for toxicologists and scientists in Sub-Sahara Africa to investigate if lead and cadmium can become additional biomarkers in the diagnosis of psychiatric disorders.
    North American Journal of Medical Sciences 08/2014; 6(8):370-6. DOI:10.4103/1947-2714.139283
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