Disturbances of mitochondrial parameters to distinguish patients with depressive episode of bipolar disorder and major depressive disorder

Abstract

Martina Zvéřová,1 Jana Hroudová,1,2 Zdeněk Fišar,1 Hana Hansíková,3 Lucie Kališová,1 Eva Kitzlerová,1 Alena Lambertová,1 Jiří Raboch1 1Department of Psychiatry, First Faculty of Medicine, Charles University and General University Hospital in Prague, 120 00 Prague 2, Czech Republic; 2Institute of Pharmacology, First Faculty of Medicine, Charles University and General University Hospital in Prague, 128 00 Prague 2, Czech Republic; 3Department of Pediatrics and Adolescent Medicine, First Faculty of Medicine, Charles University and General University Hospital in Prague, 120 00 Prague 2, Czech Republic Background: Mitochondrial dysfunctions are implicated in the pathophysiology of mood disorders. We measured and examined the following selected mitochondrial parameters: citrate synthase (CS) activity, electron transport system (ETS) complex (complexes I, II, and IV) activities, and mitochondrial respiration in blood platelets. Patients and methods: The analyses were performed for 24 patients suffering from a depressive episode of bipolar affective disorder (BD), compared to 68 patients with MDD and 104 healthy controls. BD and unipolar depression were clinically evaluated using well-established diagnostic scales and questionnaires. Results: The CS, complex II, and complex IV activities were decreased in the depressive episode of BD patients; complex I and complex I/CS ratio were significantly increased compared to healthy controls. We observed significantly decreased complex II and CS activities in patients suffering from MDD compared to controls. Decreased respiration after complex I inhibition and increased residual respiration were found in depressive BD patients compared to controls. Physiological respiration and capacity of the ETS were decreased, and respiration after complex I inhibition was increased in MDD patients, compared to controls. Increased complex I activity can be a compensatory mechanism for decreased CS and complex II and IV activities. Conclusion: We can conclude that complex I and its abnormal activity contribute to the defects in cellular energy metabolism during a depressive episode of BD. The observed parameters could be used in a panel of biomarkers that could selectively distinguish BD depression from MDD and can be easily examined from blood elements. Keywords: affective disorder, biomarker, oxidative phosphorylation, mitochondrial enzyme, platelet

Keywords

• Bipolar affective disorder Unipolar depression Blood platelet Mitochondrion Electron transport chain complexes Respiratory rate