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Mitochondrial Dysfunction and Oxidative Stress in Bipolar Disorder

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Systems Biology of Free Radicals and Antioxidants

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Abstract

Understanding the complex and multifaceted nature of bipolar disorder (BD) pathophysiology has recently expanded to include mitochondrial dysfunction and oxidative stress. Evidence of irregularities in brain energy metabolism, mitochondrial DNA mutations, and mitochondrial gene expression suggests an underlying deficiency in processes of oxidative phosphorylation, which primarily occurs through the mitochondrial electron transport chain. This is thought to be associated with overproduction of reactive oxygen species that results in increased oxidative damage in proteins, lipids, and nucleic acids in the brains of BD patients. Maladaptive oxidative modifications of these cellular macromolecules may be associated with impaired synaptic neuroplasticity and the development of functional abnormalities in the brain. Also discussed in this chapter is the research highlighting antioxidative properties of existing mood-stabilizing drugs, with considerations of novel therapeutic treatments for BD through the alleviation of oxidative stress.

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Abbreviations

4-HNE:

4-Hydroxynonenal

ACC:

Anterior cingulate cortex

BD:

Bipolar disorder

CK:

Creatine kinase

ETC:

Electron transport chain

Li+ :

Lithium

MRS:

Magnetic resonance spectroscopy

mtDNA:

Mitochondrial DNA

PCr:

Phosphocreatine

PFC:

Prefrontal cortex

PME:

Phosphomonoester

ROS:

Reactive oxygen species

VPA:

Valproate

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Authors and Affiliations

  1. Department of Psychiatry, University of British Columbia, Vancouver, BC, Canada

    Victor Tang & Jun-Feng Wang

  2. Department of Pharmacology and Therapeutics, University of Manitoba, 406 – 753 McDermot Ave., Winnipeg, MB, R3E OE3, Canada

    Jun-Feng Wang

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  1. Victor Tang
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Correspondence to Jun-Feng Wang .

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  1. Department of Pharmacology and Therapeutics, University of British Colombia, Vancouver, British Columbia, Canada

    Ismail Laher

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Tang, V., Wang, JF. (2014). Mitochondrial Dysfunction and Oxidative Stress in Bipolar Disorder. In: Laher, I. (eds) Systems Biology of Free Radicals and Antioxidants. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-30018-9_83

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