Journal of affective disorders · 2025
Mitochondrial respiration in patients with bipolar disorder: Can mitochondrial respiratory control ratios serve as state and/or trait markers?
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Hroudová Jana, Kališová Lucie, Kitzlerová Eva, Zvěřová Martina, Lambertová Alena, Fišar Zdeněk
Аннотация
BACKGROUND: Bipolar disorder (BD) is a multifactorial disorder whose pathophysiology is not fully understood. Mitochondrial dysfunction has been proposed as a part of the molecular background of BD. Mitochondrial dysfunction, manifested as changes in oxygen consumption, can be detected in peripheral blood and may serve as potential state or trait marker of BD.
METHODS: Mitochondrial respiration was analyzed in blood platelets obtained from BD patients in manic/depressive episode and in remission and compared with controls. 52 BD patients and 66 healthy age-matched controls were recruited. BD was clinically assessed using diagnostic scales and questionnaires. High-resolution respirometry was used to determine mitochondrial respiratory control ratios in both intact and permeabilized platelets.
RESULTS: In BD patients in remission, the capacity of complex II-linked respiration and reserve respiration were decreased compared to controls in intact platelets. In permeabilized platelets, physiological respiration, electron transfer system (ETS) capacity, and excess capacity were decreased in BD patients compared to controls. When comparing acute states and remissions, more pronounced changes in respiratory parameters were observed in intact platelets after treatment of depression than after treatment of mania. In permeabilized platelets, qualitative changes in respiratory parameters did not depend on the type of episode prior to pharmacotherapy.
CONCLUSIONS: Mitochondrial dysfunction is implicated in BD pathophysiology and is associated with alterations in both activity of respiratory complexes and availability of substrates for oxidative phosphorylation. In intact platelets, complex II-linked respiration/ETS capacity could be potential blood-based trait biomarker for BD. Complex I-linked respiration/ETS capacity in permeabilized platelets could serve as state marker.
METHODS: Mitochondrial respiration was analyzed in blood platelets obtained from BD patients in manic/depressive episode and in remission and compared with controls. 52 BD patients and 66 healthy age-matched controls were recruited. BD was clinically assessed using diagnostic scales and questionnaires. High-resolution respirometry was used to determine mitochondrial respiratory control ratios in both intact and permeabilized platelets.
RESULTS: In BD patients in remission, the capacity of complex II-linked respiration and reserve respiration were decreased compared to controls in intact platelets. In permeabilized platelets, physiological respiration, electron transfer system (ETS) capacity, and excess capacity were decreased in BD patients compared to controls. When comparing acute states and remissions, more pronounced changes in respiratory parameters were observed in intact platelets after treatment of depression than after treatment of mania. In permeabilized platelets, qualitative changes in respiratory parameters did not depend on the type of episode prior to pharmacotherapy.
CONCLUSIONS: Mitochondrial dysfunction is implicated in BD pathophysiology and is associated with alterations in both activity of respiratory complexes and availability of substrates for oxidative phosphorylation. In intact platelets, complex II-linked respiration/ETS capacity could be potential blood-based trait biomarker for BD. Complex I-linked respiration/ETS capacity in permeabilized platelets could serve as state marker.