Oxidative stress parameters and antioxidants in patients with bipolar disorder: Results from a meta-analysis comparing patients, including stratification by polarity and euthymic status, with healthy controls

Abstract Objective: To investigate oxidative stress markers and antioxidants in bipolar disorder (BD). Methods: 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. Results: 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. Conclusions: 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

Features Associated With Depressive Predominant Polarity and Early Illness Onset in Patients With Bipolar Disorder

Objective: The aim of this study is to determine the prevalence of three possible diagnostic specifiers, namely predominant polarity (PP) throughout illness, polarity of the first episode and early age at onset, in a sample of bipolar disorder (BD) patients and their association with important socio-demographic, clinical and course-of-illness variables. Methods: A retrospective and naturalistic study on 108 BD outpatients, who were classified according to the PP, polarity of the first episode and early age at onset ( 20 years) [vs. late (>20 years)] and were characterized by their demographics, clinical data, functionality and social support, among others features. After bivariate analyses, those variables showing certain association (P value < 0.25) with the three dependent variables were entered in logistic regression backward selection procedures to identify the variables independently associated with the PP, polarity of the first episode and early age at onset. Results: The sample consisted of 75 women ad 33 men, 74% with type I BD and 26% with type II. Around 70% had depressive PP, onset with a depressive episode and onset after age 20. Depressive PP was independently associated with depressive onset, higher score on the CGI severity scale and work disability. Onset with depressive episode was associated with type II BD, longer diagnostic delay and higher score on family disability. Early age at onset ( 20 years) was associate with younger age, longer diagnostic delay, presence of ever psychotic symptoms, current use of antipsychotic drugs and higher social support score. Conclusions: The results of this study show that BD patients with depressive PP, onset with depression and early age at onset may represent greater severity, because they are frequently associated with variables that worsen the prognosis. Our findings match up with the conclusions of two systematic reviews and we also include a disability factor (at family and work) that has not been previously reported. This work contributes to the use of polarity and age at onset in BD patients, as it can become a useful instrument in the prognostic and therapeutic applications