Can Mood-Stabilizing Agents Increase the Activity of Complexes I and II of the Electron Transport Chain and the Level of Two Tricarboxylic Acid Cycle Enzymes in Euthymic Bipolar Patients during the Early and Late Stages of the Disease?

Abstract

Bipolar disorder (BD) is associated with changes in biomarkers and mood episodes, leading to neurological damage, which may reflect alterations in cognitive functions and functionality. We analyzed the effect of four biomarkers related to metabolic energy in leukocytes. Two enzymes are related to the tricarboxylic acid (TCA) cycle (citrate synthase and succinate dehydrogenase), and two proteins are related to electron transport chain (ETC) (complexes I and II). We studied 50 euthymic patients divided into two subgroups with 25 patients (≤ 3 years and ≥ 10 years of diagnosis, from the first episode of mania) and 25 control patients. All the patients were using mood stabilizers. There were no changes in the levels of TCA cycle enzymes in the leukocytes in any subgroup. However, complex I activity showed a significant increase in patients ≤ 3 years (461.80±162.76) and ≥ 10 years (561.21±328.13) since disease onset compared to the control group (335.39±167.64) (p<0.01). Complex II activity was significantly increased in the ≥ 10 years (3.42±1.38) group compared to the ≤ 3 years (2.66±1.17) group and the control group (2.43±0.95) (p<0.01). These results suggest that stabilizing medications improve the activity of ETC complexes and stabilize TCA cycle enzymes.