Uric acid levels in subjects with bipolar disorder: A comparative meta-analysis

• Subjects with bipolar disorder have uric acid levels higher than relevant controls.
• Manic phases show increased uric acid levels as compared with depressive ones.
• Meta-regression and sensitivity analyses only partly support these findings.
• These findings have important clinical and physiopathological implications.

Previous research has hypothesised increased uric acid levels, possibly because of an amplified purinergic metabolism and a reduced adenosine activity, in subjects with bipolar disorder. This systematic review and meta-analysis aimed at estimating if individuals with bipolar disorder had uric acid levels higher than both healthy controls and subjects with major depression (trait marker hypothesis). It also tested if uric acid levels could differ in different phases of bipolar disorder (state marker hypothesis). Meta-analyses were carried out generating pooled standardized mean differences (SMDs), using random-effects models. Heterogeneity between studies was estimated using the I2 index. Relevant sensitivity and meta-regression analyses were conducted.We searched main Electronic Databases, identifying twelve studies that met our inclusion criteria. Meta-analyses showed increased uric acid levels in individuals with bipolar disorder as compared with both healthy controls (SMD = 0.65, p < 0.001, I2 = 82.9%) and those with major depression (SMD = 0.46, p < 0.001; I2 = 68.7%). However, meta-regression analyses confirmed this association only as compared with healthy controls. Finally, though uric acid levels were higher in manic/mixed phases as compared with depressive ones (SMD = 0.34; p = 0.04, I2 = 58.8%), a sensitivity analysis did not confirm the association.In sum, our meta-analysis shows that subjects with bipolar disorder have uric acid levels higher than healthy controls. The potential role of factors that might clarify the nature of this association deserves additional research.