Serum uric acid as a predictor of bipolarity in individuals with a major depressive episode

Objectives: There are no well-established biomarkers to predict the risk of conversion to bipolar disorder (BD) in patients with depression. Given the putative role of purinergic neurotransmission dysfunction in BD, the purpose of our study was to evaluate if higher serum uric acid (UA) levels could predict BD conversion in depressed inpatients.

Methods: We reviewed retrospectively the records of subjects hospitalized between June 2007 and June 2010 with a diagnosis of major depressive disorder (MDD) who had undergone routine UA levels testing at admission. At an approximate 10-year follow-up we identified subjects with a subsequent diagnosis of BD. We compared UA levels between the BD-converter and non-BD converter groups, performed Receiver operating characteristic curve analysis to evaluate the prognostic accuracy of serum UA levels and calculated the clinical utility index (CUI) as a risk biomarker for conversion to BD.

Results: The study included 250 subjects (55 "BD-converters" and 195 "No BD-converters"). "BD-converters" had significantly higher plasma UA levels compared to "No BD-converters" in their index hospitalization irrespective of gender (males: 403.84 ± 91.76 vs 270.81 ± 53.58 µmol/L; U = 94.5, P < 0.001 and females 302.19 ± 52.64 vs 202.69 ± 48.93 µmol/L; t = 10.75, P < 0.001). Serum UA levels showed a very good to excellent accuracy for predicting conversion to BD in inpatients with MDD (area under the curve [AUC]: 0.90; 95% CI: 0.86, 0.94) and had a good to excellent CUI- and a moderate to good CUI+ grading for discriminating BD-converter cases from non-BD converters.

Conclusions: Our study suggests that depressed patients with higher levels of serum UA are at greater risk of a subsequent manic or hypomanic episode. The purinergic system could prove a promising path for the search of biomarkers in BD.