Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
Neuropsychopharmacology. 2008 Oct;33(11):2551-65. doi: 10.1038/sj.npp.1301671. Epub 2008 Jan 30.

Mitochondrially mediated plasticity in the pathophysiology and treatment of bipolar disorder.

Author information

  • 1Laboratory of Molecular Pathophysiology, Department of Health and Human Services, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892, USA.

Abstract

Bipolar disorder (BPD) has traditionally been conceptualized as a neurochemical disorder, but there is mounting evidence for impairments of cellular plasticity and resilience. Here, we review and synthesize the evidence that critical aspects of mitochondrial function may play an integral role in the pathophysiology and treatment of BPD. Retrospective database searches were performed, including MEDLINE, abstract booklets, and conference proceedings. Articles were also obtained from references therein and personal communications, including original scientific work, reviews, and meta-analyses of the literature. Material regarding the potential role of mitochondrial function included genetic studies, microarray studies, studies of intracellular calcium regulation, neuroimaging studies, postmortem brain studies, and preclinical and clinical studies of cellular plasticity and resilience. We review these data and discuss their implications not only in the context of changing existing conceptualizations regarding the pathophysiology of BPD, but also for the strategic development of improved therapeutics. We have focused on specific aspects of mitochondrial dysfunction that may have major relevance for the pathophysiology and treatment of BPD. Notably, we discuss calcium dysregulation, oxidative phosphorylation abnormalities, and abnormalities in cellular resilience and synaptic plasticity. Accumulating evidence from microarray studies, biochemical studies, neuroimaging, and postmortem brain studies all support the role of mitochondrial dysfunction in the pathophysiology of BPD. We propose that although BPD is not a classic mitochondrial disease, subtle deficits in mitochondrial function likely play an important role in various facets of BPD, and that enhancing mitochondrial function may represent a critical component for the optimal long-term treatment of the disorder.

PMID:
18235426
[PubMed - indexed for MEDLINE]
Free full text
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Nature Publishing Group
    Loading ...
    Write to the Help Desk