Association Between Serum Uric Acid/Creatinine Ratio and Depressive Symptoms in Middle-Aged and Older Adults: Evidence from Two Large Population-Based Studies in China and the United States

Objective Emerging evidence suggests that serum uric acid (SUA) can modulate depressive symptoms, potentially via mechanisms involving oxidative stress. However, whether the serum uric acid/creatinine ratio (SUA/Cr)—a biomarker reflecting net uric acid production—is linked to depressive symptoms in middle-to-late life populations remains unknown. Methods Longitudinal and cross-sectional analyses were conducted utilizing nationally representative samples from two countries: the China Health and Retirement Longitudinal Study (CHARLS) for longitudinal assessment and the U.S. National Health and Nutrition Examination Survey (NHANES) for cross-sectional evaluation. Multivariable Cox and logistic regression analyses were employed to examine the relationship between the SUA/Cr and depressive symptoms. Dose-response relationships were modeled using restricted cubic splines (RCS), while sensitivity analyses assessed the stability of results. Results From CHARLS (N = 4317), multivariable Cox regression revealed an inverse relationship between SUA/Cr and depressive symptoms (P-linearity<0.05), with each 1-unit increase linked to a 3% lower risk (HR = 0.97, 95% CI = 0.94-0.99). Q4 showed reduced risk vs Q1 (HR = 0.87, 95% CI = 0.77-0.97). NHANES analysis of cross-sectional data (N = 18 677) confirmed this inverse association (P- linearity<0.05), with a 6% lower odds of significant depression per 1-unit SUA/Cr increase (OR = 0.94, 95% CI = 0.87-1.03). Q3 and Q4 had significantly lower odds vs Q1 (OR = 0.78, 95% CI = 0.64-0.95, and OR = 0.79, 95% CI = 0.65-0.98, respectively). RCS curves confirmed dose-response relationships in both cohorts. Findings remained consistent in sensitivity analyses. Conclusion Depressive symptoms in middle-to-late adulthood were found to be negatively correlated with SUA/Cr levels in longitudinal and cross-sectional analyses. These findings suggest that SUA/Cr levels may function as a biological indicator to facilitate early detection and proactive intervention for depressive disorders.