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

Abstract

| INTRODUC TI ONBipolar Disorder (BD) is one of the top 20 leading causes of disability worldwide. 1 It affects more than 1% of the population, with an estimated lifetime prevalence of 0.6% for type I BD, 0.4% for type II BD, and 1.4% for subthreshold manifestations of BD. 2 Despite the availability of effective treatments, the delay between the onset of BD and its diagnosis and management is often very long, with a pooled interval of almost 6 years. 3 Early diagnosis is difficult in clinical practice because the onset of BD is often characterized by a 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 BDconverter 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. K E Y W O R D Sbipolar disorder, major depressive disorder, uric acid

Purinergic Signaling and Related Biomarkers in Depression

“…Interestingly, subjects with bipolar disorder might have increased uric acid levels [96,97] and might benefit from drugs lowering uric acid [98]. Consistent with these findings, uric acid has been proposed as a diagnostic marker that may differentiate 'unipolar' and bipolar depression [99]. It is noteworthy that variations of peripheral levels of uric acid have been correlated with several brain functions.…”

Lower Serum Uric Acid Is Associated With Post-Stroke Depression at Discharge

“…The purinergic system has been associated with the pathophysiology of depression and is thought to influence mood, appetite, sleep, cognition, and drive through the neuromodulator adenosine and the neurotransmitter adenosine triphosphate, both of which are upstream metabolites of UA (35). Increased levels of UA are associated with decreased adenosinergic transmission and accelerated purinergic transformation, which could limit the development of depressive disorders (36). Previous studies also suggested that lower SUA levels at the onset of ischemic stroke could indicate a worse prognosis, such as increased risk of PSD, by increasing the neurological damage levels (37,38).…”

Peripheral Uric Acid as a Biomarker in Individuals with Bipolar Disorder

“…Nevertheless, a recent study indicated that UA levels in UD were lower than HC; a possible reason was the heterogeneity of subjects in the UD group because the UA diagnosis is only based on clinical symptoms at present while some patients with BD often begin with depression. It was further con rmed by a recent study that the higher UA levels might be a predictor of BD [31]. The previous study showed that sex was an important factor that could affect UA levels [19], but the study analyzed separately by sex and got similar results.…”