OBJECTIVE: In the last decade, several studies have suggested that depression is accompanied by increased oxidative stress and decreased antioxidant defenses. We tested the hypothesis that high levels of the antioxidant uric acid are associated with lower risk of hospitalization with depression and use of prescription antidepressant medication.

METHOD: We examined plasma levels of the antioxidant uric acid in 96 989 individuals from two independent cohort studies. Logistic regression and Cox proportional hazards regression models were multivariable adjusted for age, gender, alcohol, smoking, income, body mass index, C-reactive protein, hemoglobin, triglycerides, cardiovascular disease, diabetes, and intake of meat and vegetables. Results were performed separately in each study and combined in a meta-analysis.

RESULTS: In both studies, high uric acid was associated with lower risk of hospitalization as in-patient or out-patient with depression and antidepressant medication use. A doubling in uric acid was associated with an effect estimate of 0.57 (95% CI 0.49-0.65) and 0.77 (0.73-0.81) for hospitalization with depression and antidepressant medication use. The association was consistent across strata of all covariates. Results were attenuated in Cox regression analyses with less statistical power.

CONCLUSION: High plasma levels of uric acid were associated with low risk of depression hospitalization and antidepressant medication use.