Disturbances of Mitochondrial Parameters to Distinguish Patients with Depressive Episode of Bipolar Disorder and Major Depressive Disorder

Overview

Journal Neuropsychiatr Dis Treat

Publisher Dove Medical Press

Specialty Psychiatry

Date 2019 Jan 26

PMID 30679909

Citations 15

Authors

Martina Zverova

Jana Hroudova

Zdenek Fisar

Hana Hansikova

Lucie Kalisova

Eva Kitzlerova

Alena Lambertova

Jiri Raboch

Affiliations

Soon will be listed here.

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.

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References

Hirschfeld R, Lewis L, Vornik L . Perceptions and impact of bipolar disorder: how far have we really come? Results of the national depressive and manic-depressive association 2000 survey of individuals with bipolar disorder. J Clin Psychiatry. 2003; 64(2):161-74. View

Gardner A, Johansson A, Wibom R, Nennesmo I, von Dobeln U, Hagenfeldt L . Alterations of mitochondrial function and correlations with personality traits in selected major depressive disorder patients. J Affect Disord. 2003; 76(1-3):55-68. DOI: 10.1016/s0165-0327(02)00067-8. View

Renner K, Amberger A, Konwalinka G, Kofler R, Gnaiger E . Changes of mitochondrial respiration, mitochondrial content and cell size after induction of apoptosis in leukemia cells. Biochim Biophys Acta. 2003; 1642(1-2):115-23. DOI: 10.1016/s0167-4889(03)00105-8. View

Fox J, Reynolds C, Boyles J . Studying the platelet cytoskeleton in Triton X-100 lysates. Methods Enzymol. 1992; 215:42-58. DOI: 10.1016/0076-6879(92)15052-e. View

Cuellar A, Johnson S, Winters R . Distinctions between bipolar and unipolar depression. Clin Psychol Rev. 2005; 25(3):307-39. PMC: 2850601. DOI: 10.1016/j.cpr.2004.12.002. View

Stork C, Renshaw P . Mitochondrial dysfunction in bipolar disorder: evidence from magnetic resonance spectroscopy research. Mol Psychiatry. 2005; 10(10):900-19. DOI: 10.1038/sj.mp.4001711. View

Stadlmann S, Renner K, Pollheimer J, Moser P, Zeimet A, Offner F . Preserved coupling of oxidative phosphorylation but decreased mitochondrial respiratory capacity in IL-1beta-treated human peritoneal mesothelial cells. Cell Biochem Biophys. 2006; 44(2):179-86. DOI: 10.1385/CBB:44:2:179. View

Yildiz-Yesiloglu A, Ankerst D . Neurochemical alterations of the brain in bipolar disorder and their implications for pathophysiology: a systematic review of the in vivo proton magnetic resonance spectroscopy findings. Prog Neuropsychopharmacol Biol Psychiatry. 2006; 30(6):969-95. DOI: 10.1016/j.pnpbp.2006.03.012. View

Bohm M, Papezova H, Hansikova H, Wenchich L, Zeman J . Activities of respiratory chain complexes in isolated platelets in females with anorexia nervosa. Int J Eat Disord. 2007; 40(7):659-63. DOI: 10.1002/eat.20403. View

10.

Shao L, Martin M, Watson S, Schatzberg A, Akil H, Myers R . Mitochondrial involvement in psychiatric disorders. Ann Med. 2008; 40(4):281-95. PMC: 3098560. DOI: 10.1080/07853890801923753. View

11.

Rezin G, Amboni G, Zugno A, Quevedo J, Streck E . Mitochondrial dysfunction and psychiatric disorders. Neurochem Res. 2008; 34(6):1021-9. DOI: 10.1007/s11064-008-9865-8. View

12.

Jou S, Chiu N, Liu C . Mitochondrial dysfunction and psychiatric disorders. Chang Gung Med J. 2009; 32(4):370-9. View

13.

Hroudova J, Fisar Z . Activities of respiratory chain complexes and citrate synthase influenced by pharmacologically different antidepressants and mood stabilizers. Neuro Endocrinol Lett. 2010; 31(3):336-42. View

14.

Clay H, Sillivan S, Konradi C . Mitochondrial dysfunction and pathology in bipolar disorder and schizophrenia. Int J Dev Neurosci. 2010; 29(3):311-24. PMC: 3010320. DOI: 10.1016/j.ijdevneu.2010.08.007. View

15.

Sjovall F, Morota S, Hansson M, Friberg H, Gnaiger E, Elmer E . Temporal increase of platelet mitochondrial respiration is negatively associated with clinical outcome in patients with sepsis. Crit Care. 2010; 14(6):R214. PMC: 3219983. DOI: 10.1186/cc9337. View

16.

Diab Y, Thomas A, Luban N, Wong E, Wagner S, Levy R . Acquired cytochrome C oxidase impairment in apheresis platelets during storage: a possible mechanism for depletion of metabolic adenosine triphosphate. Transfusion. 2011; 52(5):1024-30. DOI: 10.1111/j.1537-2995.2011.03446.x. View

17.

Schapira A . Mitochondrial diseases. Lancet. 2012; 379(9828):1825-34. DOI: 10.1016/S0140-6736(11)61305-6. View

18.

Hroudova J, Fisar Z . In vitro inhibition of mitochondrial respiratory rate by antidepressants. Toxicol Lett. 2012; 213(3):345-52. DOI: 10.1016/j.toxlet.2012.07.017. View

19.

Parker G, McCraw S, Hadzi-Pavlovic D, Fletcher K . Costs of the principal mood disorders: a study of comparative direct and indirect costs incurred by those with bipolar I, bipolar II and unipolar disorders. J Affect Disord. 2012; 149(1-3):46-55. DOI: 10.1016/j.jad.2012.10.002. View

20.

Sjovall F, Ehinger J, Marelsson S, Morota S, Asander Frostner E, Uchino H . Mitochondrial respiration in human viable platelets--methodology and influence of gender, age and storage. Mitochondrion. 2012; 13(1):7-14. DOI: 10.1016/j.mito.2012.11.001. View