Data published in Bipolar Disorders suggest that high serum uric acid (UA) levels may predict conversion to bipolar disorder (BD) in patients with major depressive disorder (MDD). Specifically, serum UA levels may predict subsequent manic or hypomanic episodes among patients with MDD.

Investigators retrospectively reviewed the medical records of psychiatric inpatients admitted between June 2007 and June 2010 with a primary diagnosis of MDD. Eligible patients had undergone routine UA level testing at admission. At the 10-year follow-up point, researchers identified patients who had received a subsequent diagnosis of BD and compared their initial UA levels with those of nonconverters. Receiver operating characteristic curve analysis was performed to evaluate the prognostic accuracy of serum UA levels. Investigators also calculated the clinical utility index (CUI) of serum UA levels as a risk biomarker for conversion to BD.

The study cohort was composed of 250 total patients, among whom 55 (22%) were BD-converters and 195 (78%) were nonconverters. Each group had similar characteristics regarding patient age, length of inpatient stay, and number of days from hospital admission to blood collection. Although 357 of 492 participants were women, sex ratios were similar across subgroups. BD-converters had significantly higher plasma UA levels (337.31±83.56 μmol/L) compared with nonconverters (220.50±58.36 μmol/L) at initial hospitalization (P <.001). These differences between BD-converters and nonconverters were also observed within each sex subgroup (men: 403.84±91.76 vs 270.81±53.58 μmol/L; P <.001; women: 302.19±52.64 vs 202.69±48.93 μmol/L; P <.001).

Receiver operating characteristic curve analysis indicated that serum UA levels had very good to excellent prognostic accuracy in the total sample (area under the curve [AUC], 0.90; 95% CI, 0.86-0.94), and among both men only (AUC, 0.90; 95% CI, 0.80-1.00) and women only (AUC, 0.94; 95% CI, 0.91-0.97). Per CUI scores, serum UA levels had good to excellent CUI and moderate to good CUI-positive grading for discriminating converter cases from nonconverters. Using the Youden Index method, investigators identified the optimal cutoff levels for predicting bipolarity in depressed inpatients: 318.22 μmol/L for men, 240.89 μmol/L for women, and 246.84 μmol/L for the total sample.

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These results suggest that patients with MDD and higher levels of serum UA may be at greater risk for subsequent conversion to BD. Researchers concluded that the purinergic system may be a promising site of research to identify further biomarkers for BD.


dos Santos Oliveira PM, Santos V, Coroa M, et al. Serum uric acid as a predictor of bipolarity in individuals with a major depressive episode [published online October 30, 2018]. Bipolar Disord. doi: 10.1111/bdi.12708