Mitochondrial DNA copy number of peripheral blood in bipolar disorder: The present study and a meta-analysis

Yamaki, Naruhisa; Otsuka, Ikuo; Numata, Shusuke; Yanagi, Masaya; Mouri, Kentaro; Okazaki, Kenji; Boku, Shuken; Horai, Tadasu; Ohmori, Tetsuro; Sato, Osamu; Sora, Ichiro; Hishimoto, Akitoyo

doi:10.1016/j.psychres.2018.08.014

Cited by 32 publications

(24 citation statements)

References 10 publications

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“…A significant decreased mtDNAcn levels in manic patients was found in this study. The change of mtDNAcn was discussed in our previous report ( 28 ) and confirmed in later studies ( 56 , 57 ). To the best of our knowledge, this is the first study to explore the relationship between BDNF and mtDNAcn in BD.…”

Section: Discussionsupporting

confidence: 81%

Circulating Brain-Derived Neurotrophic Factor, Antioxidant Enzymes Activities, and Mitochondrial DNA in Bipolar Disorder: An Exploratory Report

Wang

et al. 2020

Front. Psychiatry

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Aim: Accumulated evidence indicates that neurotrophin deregulations, oxidative stress injury, and mitochondrial dysfunction have been involved in bipolar disorder (BD); however, their real roles in BD are unclear. Investing the possible interaction between three systems is worthwhile understanding this complex process. Methods: We measured plasma brain-derived neurotrophic factor (BDNF) level, leukocytes mitochondrial DNA copy number (mtDNAcn), and activities of antioxidant enzymes in BD patients (n = 97) and healthy controls (n = 31). Analysis of variance and linear regression analyses were performed to explore the interaction between mtDNAcn, antioxidant enzymes, and BDNF. Results: Compared with healthy controls, there were significant decreases of glutathione peroxidase activity, BDNF levels, and mtDNA content, significant increases of manganese superoxide dismutase (MnSOD) activity among BD patients (all p < 0.05). Regression analysis showed MnSOD activity had a moderate effect on BDNF (beta = 0.23, t = 8.5, p = 0.001). Copper zinc SOD and total SOD activity were significantly correlated with Hamilton Depression Scale scores in depressive patients (r = −0.38, p = 0.013; r = −0.35, p = 0.022). Unexpectedly, we observed no significant correlation between mtDNA content and BDNF in BD patients (p > 0.05). Conclusion: The findings coincide with our hypothesis that abnormal antioxidant enzymes, mtDNAcn, and peripheral BDNF may be involved in the course of BD. There were significant correlations between peripheral BDNF, antioxidant enzyme activities and mtDNAcn, suggesting that oxidative stress, mitochondrial function, and BDNF may influence each other in BD.

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Section: Discussionsupporting

confidence: 81%

Circulating Brain-Derived Neurotrophic Factor, Antioxidant Enzymes Activities, and Mitochondrial DNA in Bipolar Disorder: An Exploratory Report

Wang

et al. 2020

Front. Psychiatry

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“…For mtDNAcn measurement, patients who were clinically diagnosed with BD (n = 79, mean age ± standard deviation = 43.4 ± 12.4 years), patients with MDD (n = 44, 42.9 ± 10.8 years), and healthy controls (CON; n = 58, 48.2 ± 13.1 years) from the Osaka, Kobe, and Tokushima city areas of Japan (Hondo) (6, 18, 20, 21) were recruited between April 2013 and March 2017. All patients participated in this study via outpatient consultations.…”

Section: Methodsmentioning

confidence: 99%

“…The mtDNA copy number, or mtDNAcn, has been used as an index of mitochondrial dysfunction and investigated in many diseases, including mood disorders (15–17). Recently, our meta-analysis showed that mtDNAcn was lower in BD patients than in controls in an Asian population (18). Furthermore, a large-scale study demonstrated that mtDNAcn was higher in MDD patients than in controls (19).…”

Section: Introductionmentioning

confidence: 99%

Mitochondrial DNA Copy Number Raises the Potential of Left Frontopolar Hemodynamic Response as a Diagnostic Marker for Distinguishing Bipolar Disorder From Major Depressive Disorder

et al. 2019

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Background: Given a lack of markers, diagnoses of bipolar disorder (BD) and major depressive disorder (MDD) rely on clinical assessment of symptoms. However, the depressive mood states of BD and depressive symptoms of MDD are often difficult to distinguish, which leads to misdiagnoses, which in turn leads to inadequate treatment. Previous studies have shown that the hemodynamic responses of the left frontopolar cortex measured by near-infrared spectroscopy (NIRS) differ between BD and MDD; these hemodynamic responses are associated with altered mitochondrial metabolism; and mitochondrial DNA copy number (mtDNAcn), an index of mitochondrial dysfunction, tends to decrease in BD and increase in MDD patients. In this study, we confirmed that mtDNAcn trends in opposite directions in BD and MDD. We then determined whether mtDNAcn could enhance the utility of NIRS as a diagnostic marker to distinguish between BD and MDD. Methods: We determined mtDNAcn in peripheral blood samples from 58 healthy controls, 79 patients with BD, and 44 patients with MDD. Regional hemodynamic responses during a verbal fluency task (VFT) in 24 BD patients and 44 MDD patients, matched by age and depression severity, were monitored using NIRS. Results: Measurements of mtDNAcn were lower in BD patients and higher in MDD patients than in controls. The left frontopolar region exhibited the most significant differences in mean VFT-related oxy-Hb changes between the BD and MDD groups. Multivariate logistic regression analysis with variables including age, sex, hemodynamic response of the left frontopolar region, and mtDNAcn showed high accuracy for distinguishing BD from MDD (area under the curve = 0.917; 95% confidence interval = 0.849–0.985). For the BD group, we observed a positive correlation between hemodynamic responses in the left frontopolar region and mtDNAcn, while for the MDD group, we observed a negative correlation. Conclusions: Our findings suggest that the association between hemodynamic response and mitochondrial dysfunction in BD or MDD plays an important role in differentiating the pathophysiological mechanisms of BD from those of MDD.

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“…Regarding BD, there is an inconsistency in mtDNA copy number (mtDNAcn) studies that could be attributed to the diversity in clinical features, tissue types, and ethnicity. 71 , 152 - 155 A recent meta-analysis identified no significant differences in mtDNAcn exhibited by BD patients or controls, while an Asian-specific meta-analysis for BD-mtDNAcn studies revealed significantly lower mtDNAcn in patients with BD, with a low level of heterogeneity. 155 Moreover, mtDNAcn was inversely correlated with the number of relapses of manic episodes.…”

Section: Mitochondrial Dysfunction and Oxidative Stressmentioning

confidence: 99%

“… 71 , 152 - 155 A recent meta-analysis identified no significant differences in mtDNAcn exhibited by BD patients or controls, while an Asian-specific meta-analysis for BD-mtDNAcn studies revealed significantly lower mtDNAcn in patients with BD, with a low level of heterogeneity. 155 Moreover, mtDNAcn was inversely correlated with the number of relapses of manic episodes. 154 A possible mechanism for the lower levels of mtDNAcn could be related to DNA polymerase gamma (POLG) dysfunction due to oxidative stress.…”

Section: Mitochondrial Dysfunction and Oxidative Stressmentioning

confidence: 99%

Neurobiology of bipolar disorders: a review of genetic components, signaling pathways, biochemical changes, and neuroimaging findings

Scaini

Valvassori

Diaz

et al. 2020

Braz. J. Psychiatry

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Bipolar disorder (BD) is a chronic mental illness characterized by changes in mood that alternate between mania and hypomania or between depression and mixed states, often associated with functional impairment. Although effective pharmacological and non-pharmacological treatments are available, several patients with BD remain symptomatic. The advance in the understanding of the neurobiology underlying BD could help in the identification of new therapeutic targets as well as biomarkers for early detection, prognosis, and response to treatment in BD. In this review, we discuss genetic, epigenetic, molecular, physiological and neuroimaging findings associated with the neurobiology of BD. Despite the advances in the pathophysiological knowledge of BD, the diagnosis and management of the disease are still essentially clinical. Given the complexity of the brain and the close relationship between environmental exposure and brain function, initiatives that incorporate genetic, epigenetic, molecular, physiological, clinical, environmental data, and brain imaging are necessary to produce information that can be translated into prevention and better outcomes for patients with BD.

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Mitochondrial DNA copy number of peripheral blood in bipolar disorder: The present study and a meta-analysis

Cited by 32 publications

References 10 publications

Circulating Brain-Derived Neurotrophic Factor, Antioxidant Enzymes Activities, and Mitochondrial DNA in Bipolar Disorder: An Exploratory Report

Circulating Brain-Derived Neurotrophic Factor, Antioxidant Enzymes Activities, and Mitochondrial DNA in Bipolar Disorder: An Exploratory Report

Mitochondrial DNA Copy Number Raises the Potential of Left Frontopolar Hemodynamic Response as a Diagnostic Marker for Distinguishing Bipolar Disorder From Major Depressive Disorder

Neurobiology of bipolar disorders: a review of genetic components, signaling pathways, biochemical changes, and neuroimaging findings

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