Biological rhythms are correlated with Na+, K+-ATPase and oxidative stress biomarkers: A translational study on bipolar disorder

Abstract

BackgroundBipolar disorder (BD) is a chronic, severe, and multifactorial psychiatric disorder. Although biological rhythms alterations, sodium potassium pump (Na+, K+-ATPase) changes, and oxidative stress appear to play a critical role in the etiology and pathophysiology of BD, the inter-connection between them has not been described. Therefore this study evaluated the association between biological rhythms, Na+, K+-ATPase, and oxidative stress parameters in BD patients and the preclinical paradoxical sleep deprivation model (PSD). MethodsA translational study was conducted, including a case-control protocol with 36 BD and 46 healthy controls (HC). Subjects completed the Biological Rhythm Interview of Assessment in Neuropsychiatry (BRIAN). In addition, Erythrocyte Na+, K+-ATPase activity, and oxidative and nitrosative stress markers were assessed (4-hydroxynonenal [4-HNE], 8-isoprostane [8-ISO], thiobarbituric acid reactive substances [TBARS], carbonyl, 3-nitrotyrosine [3-nitro]). In the preclinical protocol, the same biomarkers were evaluated in the frontal cortex, hippocampus, and striatum from mice submitted to the PSD. ResultsBD patients had a significantly higher total score of BRIAN versus HCs. Additionally, individuals with BD showed decreased Na+, K+-ATPase activity and increased oxidative stress parameters compared to HC without psychiatric disorders. This difference was driven by actively depressed BD subjects. The mice submitted to the PSD also demonstrated decreased Na+, K+-ATPase activity and increased oxidative stress parameters. LimitationsBRIAN biological underpinning is less well characterized; We did not control for medication status; Sample size is limited; PSD it is not a true model of BD. ConclusionsThe present study found a significant correlation between Na+, K+-ATPase and oxidative stress with changes in biological rhythms, reinforcing the importance of these parameters to BD.