Association between serum uric acid levels and cognitive performance in first-episode drug-naïve schizophrenia: A large cross-sectional study.

BACKGROUND

Cognitive impairment is a core feature of schizophrenia (SZ). Uric acid (UA), a metabolite involved in oxidative stress and metabolic regulation, has been implicated in the pathophysiology of SZ. However, evidence regarding the association between UA and cognition in first-episode drug-naïve (FEDN) SZ remains limited. This study examined the relationship between serum UA levels and cognitive performance in patients with FEDN SZ.

METHODS

A total of 521 patients with FEDN SZ were recruited. Serum UA levels were measured, and psychopathological symptoms and cognitive performance were assessed using the Positive and Negative Syndrome Scale (PANSS) and the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), respectively. Multivariable regression, quartile-based, and subgroup analyses were conducted.

RESULTS

Higher serum UA levels were significantly associated with poorer immediate memory (standardized β = -0.171, q = 0.012) and lower RBANS total scores (standardized β = -0.146, q = 0.020) after adjustment for potential confounders. A significant association with delayed memory was also observed (standardized β = -0.141, q = 0.020), although this association was attenuated in sensitivity analyses. The observed associations were generally consistent across subgroups.

CONCLUSIONS

Elevated serum UA levels were associated with poorer cognitive performance in patients with FEDN SZ, particularly in immediate memory and global cognition. Serum UA may serve as a peripheral correlate of cognitive dysfunction. Longitudinal studies are needed to clarify the direction and causality of these associations.