Oxidative stress parameters and antioxidants in adults with unipolar or bipolar depression versus healthy controls: Systematic review and meta-analysis

To study differences in oxidative stress markers and antioxidants among patients with bipolar depression (BPD) and unipolar depression (UPD).Data sources. Electronic MEDLINE/PubMed/Cochrane Library/Scopus/TripDatabase database search until 30/06/2021.Included were articles comparing antioxidant or oxidative stress markers between adults with BPD or UPD and healthy controls (HCs).Two authors extracted data independently. Random effects meta-analysis, calculating standardized mean differences for results from ≥3 studies.Oxidative stress markers reported in 40 studies -1 published repeatedly- (UPD, studies = 30 n = 3072; their HCs, n = 2856; BPD, studies = 11 n = 393; their HCs, n = 540; with 1 study reporting on both UPD and BPD) included thiobarbituric acid reactive substances (TBARS), antioxidant uric acid and antioxidant-enhancing enzymes superoxide dismutase (SOD), catalase (CAT) and glutathione-peroxidase (GPX). Compared with HCs, UPD and BPD were associated with significantly higher levels of TBARS, without differences between UPD and BPD (P = 0.11). Compared with HCs, UPD and BPD did not differ regarding the activity of the CAT (P = 0.28), SOD (P = 0.87) and GPX (P = 0.25) enzymes. However, uric acid levels were significantly higher vs HCs in BPD than in UPD among adult patients (P = 0.004). Results were heterogenous, which, for some parameters, decreased after stratification by the blood source (serum, plasma red blood cells, whole blood).The main limitations are the small number of studies/participants in the BPD subgroup, and heterogeneity of the results.Both BPD and UPD may be associated with an impaired oxidative stress balance, with significantly higher uric acid levels vs. HCs in UPD than in BPD.