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Neurobiological basis of bipolar disorder: Mitochondrial dysfunction hypothesis and beyond


Senior Member
Neurobiological basis of bipolar disorder: Mitochondrial dysfunction hypothesis and beyond (Journal - Schizophrenia Research)

"After the proposal of mitochondrial dysfunction hypothesis of bipolar disorder, three groups performed structured interviews in patients with mitochondrial diseases (Fattal et al., 2007; Inczedy-Farkas et al., 2012; Mancuso et al., 2013) and reported that the prevalence of bipolar disorder in mitochondrial diseases is 16–21%, nearly 20 times higher than general population (Goodwin and Jamison, 2007). This suggests that having mitochondrial disease is a strong risk factor for bipolar disorder."

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."