Antioxidant uric acid in treated and untreated subjects with major depressive disorder: a meta-analysis and meta-regression.

Pathophysiological mechanisms of major depressive disorder (MDD) seem to be associated with oxidative stress pathways and altered purinergic metabolism. We conducted a systematic review and meta-analysis to estimate if subjects with MDD might have reduced levels of antioxidant uric acid, considering also potential influence of antidepressant treatment. We searched the main Electronic Databases, identifying 14 studies that met our inclusion criteria. Meta-analyses were carried out generating pooled Hedges' g and mean differences (MDs), using random-effects models. Heterogeneity across studies and risk of publication bias were estimated using standard methods. Relevant sensitivity and meta-regression analyses were conducted. Subjects with MDD had levels of uric acid lower than healthy controls (Hedges' g = -0.30; p = 0.003). Overall between-study heterogeneity was high (I 2  = 76.3%). The effect was significant among studies including drug naïve/free MDD individuals (Hedges' g = -0.55; p = 0.023), but not among those involving treated subjects (Hedges' g = -0.15; p = 0.062). Relevant quality- and heterogeneity-based sensitivity analyses, as well as meta-regressions, confirmed these findings. In addition, uric acid levels significantly, though inconsistently (I 2  = 79.2%), increased after treatment (MD = +0.71 mg/dL; p < 0.001), regardless of follow-up duration (p = 0.518). Our meta-analysis shows that subjects with MDD have lower levels of uric acid. Since antidepressant treatment seems to influence this association, our findings support the hypothesis that uric acid levels may represent a state marker of MDD. Nevertheless, the potential role of additional factors that might clarify the nature of this association deserves further research.