Lithium Monotherapy Increases Nitric Oxide Levels During Depressive Episodes in Bipolar Disorder

Abstract

Background: Nitric Oxide (NO) is precursor of peroxynitrite, a molecule which causes oxidative stress. Several studies have associated bipolar disorder (BD) with altered NO and oxidative stress. Besides that, evidences suggest a dual role of NO in depression, since both increase or decrease in NO levels have been associated with antidepressant efficacy in preclinical models. The present study evaluates NO in subjects with bipolar depression before and after a 6-week lithium treatment. Also, NO in patients and controls was compared. Methods: Patients with BD in a depressive episode (n=22) were treated with lithium monotherapy for 6 weeks. Blood samples were collected at baseline and after 6-week lithium treatment, also compared to healthy controls (n=28). NO in patients at baseline and at endpoint and in healthy controls was measured with chemiluminescence method. Results: Patients in a depressive episode had an increase in NO levels from baseline to endpoint (Wilcoxon Signed Ranks Test, z=-2.11, p=0.035). NO levels showed no difference in patients compared to healthy controls. Conclusions: This is the first study evaluating lithium effects on NO levels. Increased NO after lithium treatment suggests a potential role of NO pathways in the therapeutics of mood disorders.