Differential Mitochondrial DNA Copy Number in Three Mood States of Bipolar Disorder

Overview

Journal BMC Psychiatry

Publisher Biomed Central

Specialty Psychiatry

Date 2018 May 27

PMID 29801445

Citations 25

Authors

Dong Wang

Zongchang Li

Weiqing Liu

Jun Zhou

Xiaoqian Ma

Jinsong Tang

Xiaogang Chen

Affiliations

Soon will be listed here.

Abstract

Background: Accumulating evidences indicated that mitochondrial abnormalities were associated with bipolar disorder. As a sensitive index of mitochondrial function and biogenesis, Mitochondrial DNA copy number (mtDNAcn) may be involved in the pathophysiology of bipolar disorder.

Methods: Leukocyte relative mtDNAcn was measured by quantitative polymerase chain reaction in subjects with BD (n = 131) in manic, depressive, and euthymic symptoms. Thirty-four healthy individuals were used as comparison control. BD clinical symptomatology was evaluated by Young Mania Rating Scale (YMRS), Hamilton Depression Scale (HAM-D), Clinical Global Impression-Bipolar Disorder-Severity of Illness Scale (CGI-BD-S), and the Positive and Negative Syndrome Scale (PANSS).

Results: Compared to healthy controls, BD patients with manic and depressive symptoms presented significantly decreased mtDNAcn levels (p-value = 0.009 and 0.041, respectively). No significant differences were detected in mtDNAcn between euthymic patients and healthy controls. The mtDNAcn was negatively correlated with the number of relapses in manic patients (β = - 0.341, p = 0.044).

Conclusions: Our study described the first evidence of (1) a significant decline of mtDNAcn in manic BD patients, (2) a similar decreased level of mtDNAcn between manic and depressed BD patients, (3) a negative correlation of mtDNAcn with number of relapses in patients suffering from manic states. Alterations of mtDNAcn in manic and depressed patients, which may reflect disturbances of energy metabolism, supported the role of mitochondrial abnormalities in the pathophysiology of BD.

Citing Articles

The Association Between Periodontal Inflamed Surface Area (PISA), Inflammatory Biomarkers, and Mitochondrial DNA Copy Number.

Mance Kristan R, Jurgec S, Potocnik U, Marhl M, Gaspersic R J Clin Med. 2025; 14(1.

PMID: 39797107 PMC: 11721330. DOI: 10.3390/jcm14010024.

Impaired mitochondrial function in bipolar disorder and alcohol use disorder: a case study using F-BCPP-EF PET imaging of mitochondrial Complex I.

Wigstrom T, Roytman S, Bohnen J, Paalanen R, Griggs A, Vangel R Psychoradiology. 2024; 4:kkae014.

PMID: 39399447 PMC: 11467810. DOI: 10.1093/psyrad/kkae014.

Telomere Length as a Marker of Suicidal Risk in Schizophrenia.

Zakharova N, Bravve L, Mamedova G, Kaydan M, Ershova E, Martynov A Consort Psychiatr. 2024; 3(2):37-47.

PMID: 39045115 PMC: 11262099. DOI: 10.17816/CP171.

Integrating mitoepigenetics into research in mood disorders: a state-of-the-art review.

Ceylan D, Arat-Celik H, Aksahin I Front Physiol. 2024; 15:1338544.

PMID: 38410811 PMC: 10895490. DOI: 10.3389/fphys.2024.1338544.

Mitochondrial DNA oxidation, methylation, and copy number alterations in major and bipolar depression.

Ceylan D, Karacicek B, Tufekci K, Aksahin I, Senol S, Genc S Front Psychiatry. 2024; 14:1304660.

PMID: 38161720 PMC: 10755902. DOI: 10.3389/fpsyt.2023.1304660.

References

Woods S . Chlorpromazine equivalent doses for the newer atypical antipsychotics. J Clin Psychiatry. 2003; 64(6):663-7. DOI: 10.4088/jcp.v64n0607. View

Bersani F, Morley C, Lindqvist D, Epel E, Picard M, Yehuda R . Mitochondrial DNA copy number is reduced in male combat veterans with PTSD. Prog Neuropsychopharmacol Biol Psychiatry. 2015; 64:10-7. DOI: 10.1016/j.pnpbp.2015.06.012. View

Muller D, Zai C, Shinkai T, Strauss J, Kennedy J . Association between the DAOA/G72 gene and bipolar disorder and meta-analyses in bipolar disorder and schizophrenia. Bipolar Disord. 2011; 13(2):198-207. DOI: 10.1111/j.1399-5618.2011.00905.x. View

Ueno H, Nishigaki Y, Kong Q, Fuku N, Kojima S, Iwata N . Analysis of mitochondrial DNA variants in Japanese patients with schizophrenia. Mitochondrion. 2009; 9(6):385-93. DOI: 10.1016/j.mito.2009.06.003. View

Bertolino A, Frye M, Callicott J, Mattay V, Rakow R, Shelton-Repella J . Neuronal pathology in the hippocampal area of patients with bipolar disorder: a study with proton magnetic resonance spectroscopic imaging. Biol Psychiatry. 2003; 53(10):906-13. DOI: 10.1016/s0006-3223(02)01911-x. View

Kageyama Y, Kasahara T, Kato M, Sakai S, Deguchi Y, Tani M . The relationship between circulating mitochondrial DNA and inflammatory cytokines in patients with major depression. J Affect Disord. 2017; 233:15-20. DOI: 10.1016/j.jad.2017.06.001. View

Chang C, Jou S, Lin T, Lai T, Liu C . Mitochondria DNA change and oxidative damage in clinically stable patients with major depressive disorder. PLoS One. 2015; 10(5):e0125855. PMC: 4422713. DOI: 10.1371/journal.pone.0125855. View

Liu C, Tsai C, Kuo C, Chen H, Lii C, Ma Y . Oxidative stress-related alteration of the copy number of mitochondrial DNA in human leukocytes. Free Radic Res. 2004; 37(12):1307-17. DOI: 10.1080/10715760310001621342. View

Sousa R, Uno M, Zanetti M, Shinjo S, Busatto G, Gattaz W . Leukocyte mitochondrial DNA copy number in bipolar disorder. Prog Neuropsychopharmacol Biol Psychiatry. 2013; 48:32-5. DOI: 10.1016/j.pnpbp.2013.09.002. View

10.

Sabunciyan S, Kirches E, Krause G, Bogerts B, Mawrin C, Llenos I . Quantification of total mitochondrial DNA and mitochondrial common deletion in the frontal cortex of patients with schizophrenia and bipolar disorder. J Neural Transm (Vienna). 2007; 114(5):665-74. DOI: 10.1007/s00702-006-0581-8. View

11.

Kvajo M, Dhilla A, Swor D, Karayiorgou M, Gogos J . Evidence implicating the candidate schizophrenia/bipolar disorder susceptibility gene G72 in mitochondrial function. Mol Psychiatry. 2007; 13(7):685-96. DOI: 10.1038/sj.mp.4002052. View

12.

Hartmann N, Reichwald K, Wittig I, Drose S, Schmeisser S, Luck C . Mitochondrial DNA copy number and function decrease with age in the short-lived fish Nothobranchius furzeri. Aging Cell. 2011; 10(5):824-31. DOI: 10.1111/j.1474-9726.2011.00723.x. View

13.

Pfaffenseller B, Fries G, Wollenhaupt-Aguiar B, Colpo G, Stertz L, Panizzutti B . Neurotrophins, inflammation and oxidative stress as illness activity biomarkers in bipolar disorder. Expert Rev Neurother. 2013; 13(7):827-42. DOI: 10.1586/14737175.2013.811981. View

14.

Li Z, Hu M, Zong X, He Y, Wang D, Dai L . Association of telomere length and mitochondrial DNA copy number with risperidone treatment response in first-episode antipsychotic-naïve schizophrenia. Sci Rep. 2015; 5:18553. PMC: 4683467. DOI: 10.1038/srep18553. View

15.

Kakiuchi C, Ishiwata M, Kametani M, Nelson C, Iwamoto K, Kato T . Quantitative analysis of mitochondrial DNA deletions in the brains of patients with bipolar disorder and schizophrenia. Int J Neuropsychopharmacol. 2005; 8(4):515-22. DOI: 10.1017/S1461145705005213. View

16.

Kasahara T, Ishiwata M, Kakiuchi C, Fuke S, Iwata N, Ozaki N . Enrichment of deleterious variants of mitochondrial DNA polymerase gene (POLG1) in bipolar disorder. Psychiatry Clin Neurosci. 2016; 71(8):518-529. DOI: 10.1111/pcn.12496. View

17.

Cai N, Chang S, Li Y, Li Q, Hu J, Liang J . Molecular signatures of major depression. Curr Biol. 2015; 25(9):1146-56. PMC: 4425463. DOI: 10.1016/j.cub.2015.03.008. View

18.

Rizzo L, Costa L, Mansur R, Swardfager W, Belangero S, Grassi-Oliveira R . The theory of bipolar disorder as an illness of accelerated aging: implications for clinical care and research. Neurosci Biobehav Rev. 2014; 42:157-69. DOI: 10.1016/j.neubiorev.2014.02.004. View

19.

Xing J, Chen M, Wood C, Lin J, Spitz M, Ma J . Mitochondrial DNA content: its genetic heritability and association with renal cell carcinoma. J Natl Cancer Inst. 2008; 100(15):1104-12. PMC: 2720693. DOI: 10.1093/jnci/djn213. View

20.

Sigitova E, Fisar Z, Hroudova J, Cikankova T, Raboch J . Biological hypotheses and biomarkers of bipolar disorder. Psychiatry Clin Neurosci. 2016; 71(2):77-103. DOI: 10.1111/pcn.12476. View