Exploring the association between bipolar disorder and uric acid: A mediation analysis

Objective: Recent evidence shows that bipolar disorder might be associated with a purinergic system dysfunction. This study aimed at (i) testing the association between bipolar disorder and uric acid serum levels, and (ii) clarifying whether this relationship is mediated by metabolic syndrome and other relevant metabolic parameters. Methods: Patients consecutively admitted to a Mental Health Inpatient Unit, with a diagnosis of bipolar disorder or other severe mental disorders, and an appropriate healthy control sample, were included in this cross-sectional, exploratory study. We performed linear regression analyses, to explore factors associated with uric acid levels, and formal tests of mediation to assess mediating effect of candidate variables. Results: 176 individuals with mental disorders and 89 healthy controls met inclusion criteria. Bipolar disorder was the only diagnostic subgroup significantly associated with increased uric acid levels. Furthermore, male gender, metabolic syndrome, as well as abdominal circumference and triglycerides levels, had a significant effect on uric acid. Relevant mediation analyses showed that the estimated effect between bipolar disorder and uric acid levels was only partially mediated by metabolic abnormalities. Conclusion: This study suggests a direct association between bipolar disorder and uric acid levels, only partially mediated by metabolic abnormalities. It seems consistent with results of previous studies highlighting a purinergic dysfunction in bipolar disorder and the role that purinergic modulators, lowering uric acid levels, could have in clinical practice.