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

Abstract

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; mitochondrial enzyme; oxidative phosphorylation; platelet.

Figure 1

(A) Activities of mitochondrial enzymes in blood platelets of patients with BD in depressive episode, patients with MDD, and controls. (B) Activities of mitochondrial complexes normalized for CS activity in blood platelets of patients with BD in depressive episode, patients with MDD, and controls. Notes: Complex I – NADH:ubiquinone reductase, complex II – succinate dehydrogenase (quinone), and complex IV – cytochrome c oxidase. Mean ± SD is shown (24 BD patients, 68 MDD patients, and 104 controls). Significantly different mean values are marked by *P<0.05, **P<0.01, and ***P<0.001. Abbreviations: BD, bipolar disorder; C, complex; CS, citrate synthase; MDD, major depressive disorder.

Figure 2

(A) Mitochondrial respiration in intact platelets of patients with BD in depressive episode, patients with MDD, and controls. (B) Mitochondrial respiration in intact platelets of patients with BD in depressive episode, patients with MDD, and controls, normalized to ETS capacity (ETSC). Notes: PR was measured in diluted platelet-rich plasma; LEAK was measured after the addition of oligomycin; ETSC was determined by titration with uncoupler (FCCP); Rot was measured after the addition of rotenone. Final addition of antimycin A induced ROX, which was subtracted from all other respiratory rates. The mean ± SD is shown. Significantly different mean values are marked by *P<0.05, **P<0.01, and ***P<0.001. Abbreviations: BD, bipolar disorder; C, complex; ROT, respiration after complex I inhibition; CS, citrate synthase; LEAK, nonphosphorylating respiration; MDD, major depressive disorder; NetPR, net physiological respiration; PR, physiological respiration; ROX, residual oxygen consumption.