In a 5-year longitudinal analysis of prodromal PD participants from PPMI (61 with complete follow-up), lower baseline serum uric acid independently predicted incident depression (HR=0.776) after adjustment, alongside higher MDS‑UPDRS I scores.

This provides a prospective biomarker for early identification of depression risk in prodromal PD and implicates oxidative‑stress/urate pathways as mechanistically relevant and potentially targetable, though causality and therapeutic utility remain unproven and sample size is limited.

Depression, as an important prodromal non-motor manifestation of Parkinson's disease (PD), its early predictive indicators remain unclear. Although cross-sectional studies suggest an association between serum uric acid (UA) levels and depression in PD, longitudinal evidence in the prodromal period is lacking. This study innovatively conducted a 5-year longitudinal study in a population with prodromal Parkinson's disease (pPD), revealing for the first time the longitudinal association between serum UA levels and the development of depression. At baseline, we selected 460 pPD patients from the Parkinson's Progression Markers Initiative (PPMI) database. Eventually, 61 participants completed a 5-year longitudinal study with annual assessments. Predictor variables were selected through univariate Cox analysis and LASSO regression, with multivariate Cox regression models employed to assess the independent association between serum UA levels and incident depression in the pPD cohort. At baseline, 18.9 % of pPD patients developed depression, and the cumulative incidence rates of depression during the 5-year follow-up period were 34.43 %, 49.18 %, 57.38 %, 62.30 % and 63.93 %, respectively. Multivariate Cox regression analysis, adjusted for covariates including sex and age, identified a higher Movement Disorder Society Unified Parkinson's Disease Rating Scale Part I (MDS-UPDRS I) score (HR = 1.177, 95 % CI 1.093-1.267, P < 0.001) and lower serum UA levels (HR = 0.776, 95 % CI 0.619-0.974, P = 0.029) as independent risk factors for incident depression in the pPD cohort. Our study shows that lower serum UA levels can independently predict the risk of depression in pPD, providing a new biomarker for the early identification of high-risk populations.