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

Dong Wang,Weiqing Liu,Zongchang Li,Xiaogang Chen,Jun Zhou,Jinsong Tang,Xiaoqian Ma

doi:10.1186/s12888-018-1717-8

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.

Highlights

Accumulating evidences indicated that mitochondrial abnormalities were associated with bipolar disorder
Healthy controls with substance use, history of mental or neurological disorders, serious medical disorders, positive pregnancy test or lactation were excluded from the study
Bipolar disorder (BD) patients and healthy controls did not differ in terms of age, gender, body mass index (BMI), months of education

Summary

Introduction

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. Many systems and pathways have been involved in the pathophysiology of BD together containing signal transduction pathways, various neurotransmitter abnormalities, mitochondrial and metabolic dysfunctions and so on [1]; the definitive mechanisms of BD remains to be fully elucidated. Mitochondria serve as key organelles in eukaryotic cells, well known for synthesizing adenosine triphosphate (ATP) from glucose by oxidative phosphorylation for energy production. The energy source of neurons relies primarily on mitochondrial oxidative phosphorylation. Without protection of histones and due to limited DNA repair capacity, these mtDNA is very prone to oxidative or genotoxic injury. Mitochondria may increase their own copy number to compensate for

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Results

Conclusion