Abstract
To investigate oxidative stress markers and antioxidants in bipolar disorder (BD). Electronic MEDLINE/PubMed/Cochrane-Library/Scopus/TripDatabase search until 06/30/2019 for studies comparing antioxidant or oxidative stress markers between BD and healthy controls (HCs). Standardized mean differences (SMD) and 95% confidence intervals (CIs) were calculated for≥3 studies. Forty-four studies (n=3,767: BD=1,979; HCs=1,788) reported on oxidative stress markers malondialdehyde (MDA), thiobarbituric acid reactive substances (TBARS), and total nitrites; antioxidants glutathione (GSH), uric acid, and zinc; or antioxidantenhancing enzymes superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX), and GSH-transferase (GST). Compared with HCs, BD was associated with higher GST (P=.01), CAT (P=.02), nitrites (P<.0001), TBARS (P<.0001), MDA (P=.01), uric acid (P<.0001), and lower GSH (P=.006), without differences in SOD, GPX, and zinc. Compared to HCs, levels were higher in BD-mania for TBARS (P<.0001) and uric acid (P<.0001); in BD-depression for TBARS (P=.02); and BD-euthymia for uric acid (P=.03). Uric acid levels were higher in BD-mania vs BD-depression (P=.002), but not vs BD euthymia. TBARS did not differ between BD-mania and BD-depression. Medication-free BD-mania patients had higher SOD (P=.02) and lower GPX (P<.0001) than HCs. After treatment, BD did not differ from HCs regarding SOD and GPX. Beyond a single biomarker of oxidative stress, the combination of several parameters appears to be more informative for BD in general and taking into account illness polarity. BD is associated with an imbalance in oxidative stress with some phase-specificity for uric acid and TBARS and possible treatment benefits for SOD and GPX. Future studies should take into account confounding factors that can modify oxidative stress status and simultaneously measure oxidative stress markers and antioxidants including different blood sources.
Highlights
Severe mental disorders as well as cardiovascular diseases are associated with high rates of disability and mortality.[1,2,3,4] The reported lifetime prevalence in the United States and worldwide is 1.0% and 0.6% for type I bipolar disorder (BD); 1.1% and 0.4% for type II BD;, and 2.4% and 1.4% of subthreshold BD.[5,6] despite this relatively low prevalence, BD is associated with significant disability-adjusted life years.[7]
Compared with healthy controls (HCs), the antioxidant status, pooled superoxide dismutase (SOD) + CAT levels were significantly higher in patients with mania or depression pooled (SMD = 1.05; 95% confidence intervals (CIs), 0.28 to 1.81; P = .007; I2 = 96%), without significant differences in patients with euthymia (SMD = −0.31; 95% CI, −1.01 to 0.39; P = .39; I2 = 88%)
Our results support the hypothesis that oxidative stress plays an important role in BD, based on other work, it seems that there is some overlap with other psychiatric disorders, eg, depression and psychosis,[54,55] as shown for inflammatory markers.[69]
Summary
Severe mental disorders as well as cardiovascular diseases are associated with high rates of disability and mortality.[1,2,3,4] The reported lifetime prevalence in the United States and worldwide is 1.0% and 0.6% for type I bipolar disorder (BD); 1.1% and 0.4% for type II BD;, and 2.4% and 1.4% of subthreshold BD.[5,6] despite this relatively low prevalence, BD is associated with significant disability-adjusted life years.[7]. In order to prevent the cognitive and functional consequences of BD it is necessary to make the correct diagnosis and to prescribe the correct treatment in the early phases of the disease To this end, new and reliable biomarkers should be developed in Psychiatry to identify different disease stages just as other medical specialties do in their everyday clinical practice.[31] different studies point to alterations in antioxidant enzymes among patients with BD,[32,33,34] two previous meta-analyses showed no significant differences in the antioxidant-enzyme defenses in patients with BD compared to healthy controls (HCs).[35,36] different affective phases of BD were not taken into account in these two meta-analyses, nor was the effect of different pharmacological treatments. The aim of the present study was to analyze and synthesize existing evidence on oxidative stress markers and antioxidant parameters in patients with BD during its different polarities
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