Neuroinflammation and neuroprogression produced by oxidative stress in euthymic bipolar patients with different onset disease times

Abstract

Bipolar disorder (BD) is associated with systemic toxicity, represented by changes in biomarkers associated with mood episodes, leading to neurological damage, which may reflect cognitive functions and functionality and the progression of the disease. We aimed to analyze the effect of four biomarkers, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), and thiobarbituric acid reactive substances (TBA-RS), related to oxidative stress in BD and to correlate them with cognitive functions and functionality. We studied 50 bipolar types I/II patients in the euthymic phase, which was divided into two subgroups with 25 patients each (≤ 3 years and ≥ 10 years of diagnosis, from the first episode of mania) and 25 control patients. To analyze frontal cognitive functions and functionality, we used the Frontal Assessment Battery (FAB) and Functioning Assessment Short Test (FAST) tests, respectively. The scores of the FAST and FAB tests showed an increase and decrease respectively, in both bipolar groups, when compared to the control group, demonstrating impairment in cognitive functions and functionality since the disease onset. In addition, changes occurred in all six domains of the FAST test, and in four domains of the FAB test in bipolar patients when compared to the control group. Regarding oxidative stress biomarkers, we did not find changes in SOD and GSH-Px activities; however, a significant increase in CAT activity and lipid peroxidation was observed in both groups, although the patients were euthymic and medicated. These results allow us to raise the hypothesis that since the beginning of the disease, the euthymic bipolar patient has presented a level of oxidative stress, which gets worse with the evolution of the disease, promoting impairments in the frontal cognitive functions and functionality gradually.