Mitochondrial DNA content and oxidation in bipolar disorder and its role across brain regions

D F Bodenstein,B Navaid,N C Brown,H K Kim,L T Young,A C Andreazza

doi:10.1038/s41537-019-0089-5

Abstract

The underlying pathology of bipolar disorder remains unknown, though evidence is accumulating to support a role of mitochondrial dysfunction. In this study, we aim to investigate electron transport chain complex I subunit NDUFS7 protein expression; mtDNA content; common deletion; and oxidation in the Broadmann area 24 (BA24), cerebellum, hippocampus, and prefrontal cortex from patients with bipolar disorder, schizophrenia, and non-psychiatric controls. Here, we demonstrate no changes in NDUFS7 in BA24, cerebellum or hippocampus, increases in mtDNA content in hippocampus of patients with bipolar disorder, and decreases in mtDNA oxidation in patients with bipolar disorder and schizophrenia, respectively. Paired analysis between BA24 and cerebellum reveal increases within NDUFS7 levels and mtDNA content in cerebellum of patients with bipolar disorder or schizophrenia. We found a positive correlation between NDUFS7 and mtDNA content (ND4 and ND5) when combining brain regions. Our study supports the involvement of mitochondrial dysfunction in bipolar disorder and schizophrenia.

Highlights

Bipolar disorder (BD) is a severe disorder characterized by alternating episodes of mania and depression, which significantly impact the quality of life and lifestyle of the patient, as well as that of their partners and family members.[1,2,3] BD affects roughly 1–3% of the population worldwide,[4] regardless of socioeconomic status, race or nationality
The results reveal that in HYP samples, mtDNA content for MTND4 and MT-ND5 were significantly increased in patients with BD compared to CTL, controlling for PMI as it demonstrated a correlation with mitochondrial DNA content (Fig. 2a)
Mitochondrial dysfunction plays an important role in BD in the prefrontal cortex demonstrated by reduced electron transport chain (ETC) complex assembly and increased oxidative damage.[9,10,17] mtDNA depletion syndrome is the most common cause of reduced ETC complex assembly and is a major source of reactive oxygen species (ROS)

Summary

Introduction

Bipolar disorder (BD) is a severe disorder characterized by alternating episodes of mania and depression, which significantly impact the quality of life and lifestyle of the patient, as well as that of their partners and family members.[1,2,3] BD affects roughly 1–3% of the population worldwide,[4] regardless of socioeconomic status, race or nationality It is among the leading causes of disability in young adults due to its impact on cognitive and functional capabilities.[1,2] Patients often report impairment in work, social and familial relations, even after symptoms subside,[2,5] and are two to three times more likely to divorce or separate from their partners.[3]. These stressors and challenges can precipitate depressive or manic episodes, leading to further impairment and continuing the cycle.[5,6]

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Methods

Conclusion