title: Neurobiological basis of bipolar disorder: Mitochondrial dysfunction hypothesis and beyond.
abstract: Bipolar disorder is one of two major psychotic disorders together with schizophrenia and causes severe psychosocial disturbance. Lack of adequate animal models hampers development of new mood stabilizers. We proposed a mitochondrial dysfunction hypothesis and have been studying the neurobiology of bipolar disorder based on this hypothesis. We showed that deletions of mitochondrial DNA (ΔmtDNA) play a pathophysiological role at least in some patients with bipolar disorder possibly by affecting intracellular calcium regulation. Mutant polymerase γ transgenic mice that accumulate ΔmtDNA in the brain showed recurrent spontaneous depression-like episodes which were prevented by a serotonin-selective reuptake inhibitor and worsened by lithium withdrawal. The animal model would be useful to develop new mood stabilizers.
authors.affiliation: Laboratory for Molecular Dynamic of Mental Disorders, RIKEN Brain Science Institute, Japan. Electronic address: kato@brain.riken.jp.
authors.forename: Tadafumi
authors.initials: T
authors.lastname: Kato
mesh_terms: D000818:Animals; D001714:Bipolar Disorder / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D004272:DNA, Mitochondrial; D006801:Humans; D008928:Mitochondria / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D028361:Mitochondrial Diseases / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism
chemical_list: D004272:DNA, Mitochondrial
keywords: Animal model; Bipolar disorder; Calcium; Mitochondrial DNA; Paraventricular thalamic nucleus