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Mitochondrially Mediated Plasticity in the Pathophysiology and Treatment of Bipolar Disorder
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Mitochondrially Mediated Plasticity in the Pathophysiology and Treatment of Bipolar Disorder
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Journal Article
Mitochondrially Mediated Plasticity in the Pathophysiology and Treatment of Bipolar Disorder
2008
Overview
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.
Publisher
Springer International Publishing,Nature Publishing,Nature Publishing Group
Subject
Adult and adolescent clinical studies
/ Animals
/ Biological and medical sciences
/ Bipolar Disorder - pathology
/ Bipolar Disorder - physiopathology
/ Humans
/ Medicine
/ Neuronal Plasticity - physiology
/ Pharmacology. Drug treatments
/ Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer
