Abstract
BACKGROUND: Despite the fact that observational studies have reported associations between serum uric acid (SUA) and depressive symptoms risk in East Asian populations, there is a lack of evidence demonstrating a causal relationship between them. This study aimed to perform a comprehensive assessment of the relationship between SUA and depressive symptoms. METHODS: This study included two cohort studies and a two-sample Mendelian randomization study. The cross-sectional cohort was derived from the China Health and Retirement Longitudinal Study (CHARLS) wave 3 (in 2015), and the baseline data of participants were extracted from the CHARLS wave 1(in 2011), excluding those with depressive symptoms in 2011 and forming a longitudinal cohort from 2011 to 2015. Logistic multiple regression was performed to investigate the cross-sectional and longitudinal associations of SUA with depressive symptoms in the two cohorts. Furthermore, we performed two-sample Mendelian randomization analyses to explore the potential causal relationships between them. RESULTS: We included two cohorts of 9056 and 3177 individuals respectively. Logistic regression showed that individual with higher SUA levels had a lower risk of depressive symptoms (OR = 0.921; 95%CI: 0.886-0.957) in the cross-sectional cohort. However, neither the baseline SUA level (OR = 1.055, 95%CI: 0.961-1.157) nor the change in SUA level (OR = 0.945, 95%CI: 0.656-1.363) affected the depressive symptoms 4 years later in the longitudinal cohort. The two-sample MR showed that there was no genetic causal relationship between SUA and depression (OR(IVW_MRE)= 1.071, 95% CI: 0.926-1.238). CONCLUSIONS: SUA and depressive symptoms are associated, with lower SUA levels observed in middle-aged and older participants with depressive symptoms; however, no causal evidence supports their relationship.