Differential mitochondrial DNA copy number in three mood states of bipolar disorder

Abstract

BackgroundAccumulating 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.MethodsLeukocyte 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).ResultsCompared 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).ConclusionsOur 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.Electronic supplementary materialThe online version of this article (10.1186/s12888-018-1717-8) contains supplementary material, which is available to authorized users.

Major Depressive Disorder is Associated with Impaired Mitochondrial Function in Skin Fibroblasts

“…Mitochondrial content is an important quantitative measure, since the mitochondrial mass is dependent on intact mitochondrial dynamics and influences mitochondrial bioenergetics [20,21]. In the present study, we analyzed the mtDNA copy number as a quantitative measure for mitochondrial mass or density [13,22,23] and could not detect significant differences between MDD fibroblasts and non-depressive controls. This finding suggests that the altered respiratory parameters and bioenergetic properties, which we found in MDD fibroblasts cannot be attributed to differences in the mitochondrial mass.…”

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

“…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][153][154][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.…”

“…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. In fact, recent studies have demonstrated that individuals with BD present downregulation of POLG, the replicative polymerase responsible for maintaining mtDNA, as well as downregulation of the DNA repair enzyme, 8-oxoguanine-DNA glycosylase 1 (OGG1).…”

Novel Complex Interactions between Mitochondrial and Nuclear DNA in Schizophrenia and Bipolar Disorder

“…A small association study of BD showed an association with T195C [1] and also with a 5178C/10398A mtDNA haplotype [8]. A decreased mtDNA copy number in BD has been reported [10, 56, 57]. However, pathway analysis of GWAS of BD did not reveal an association of pathways and mitochondria dysfunction [58].…”