Department of Medicine and Surgery, University of Milano Bicocca, Via Cadore 48, 20900, Monza, Italy.
Division of Psychiatry, University College London, London, UK.
Eur Arch Psychiatry Clin Neurosci. 2018 Mar;268(2):119-127. doi: 10.1007/s00406-017-0817-7. Epub 2017 Jun 15.
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 = 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 = 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.
重度抑郁症（MDD）的病理生理机制似乎与氧化应激途径和嘌呤代谢改变有关。我们进行了系统评价和荟萃分析，以评估 MDD 患者的抗氧化尿酸水平是否可能降低，同时还考虑了抗抑郁治疗的潜在影响。我们搜索了主要的电子数据库，确定了 14 项符合我们纳入标准的研究。使用随机效应模型进行荟萃分析，生成合并的 Hedges'g 和均值差异（MDs）。使用标准方法评估研究之间的异质性和发表偏倚的风险。进行了相关的敏感性和荟萃回归分析。与健康对照组相比，MDD 患者的尿酸水平较低（Hedges'g=-0.30;p=0.003）。总体而言，研究之间的异质性很高（I²=76.3%）。在包括未接受药物治疗/无药物治疗的 MDD 个体的研究中，这种影响是显著的（Hedges'g=-0.55;p=0.023），但在涉及接受治疗的受试者的研究中则不显著（Hedges'g=-0.15;p=0.062）。基于质量和异质性的相关敏感性分析以及荟萃回归证实了这些发现。此外，尿酸水平在治疗后显著但不一致地升高（I²=79.2%）（MD=+0.71mg/dL;p<0.001），无论随访时间如何（p=0.518）。我们的荟萃分析表明，MDD 患者的尿酸水平较低。由于抗抑郁治疗似乎会影响这种关联，我们的研究结果支持尿酸水平可能代表 MDD 状态标志物的假说。然而，需要进一步研究其他可能阐明这种关联本质的因素的潜在作用。
