Mitochondrial dysfunction in schizophrenia: a possible linkage to dopamine.
Mitochondria are not only the principal source of high energy intermediates, but play an important role in intracellular calcium buffering, are main producers of reactive oxygen species, and are the source of pro- and antiapoptotic key factors. Moreover, the mitochondria are of a ubiquitous nature and the respiratory chain has a dual genetic basis, i.e. the mitochondrial and the nuclear DNAs. Thus mitochondrial impairment could provide an explanation for the tremendous heterogeneity of clinical and pathological manifestations in schizophrenia. This article reviews several independent lines of evidence that suggest an involvement of mitochondrial dysfunction in schizophrenia. Among them are altered cerebral energy metabolism, mitochondrial hypoplasia, dysfunction of the oxidative phosphorylation system and altered mitochondrial related gene expression. In addition, the interaction between dopamine, a predominant etiological factor in schizophrenia, and mitochondrial respiration is considered as a possible mechanism underlying the hyper- and hypo-activity cycling in schizophrenia. Understanding the role of mitochondria in schizophrenia may encourage novel treatment approaches, the identification of candidate genes and new insights into the pathophysiology and etiology of the disorder.
Ben-Shachar
Dorit
D
Laboratory of Psychobiology, The Department of Psychiatry, Rambam Medical Center and B. Rappaport Faculty of Medicine, Technion IIT, Haifa, Israel. shachar@tx.technion.ac.il
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology; D001921:Brain / Q000503:physiopathology; D004298:Dopamine / Q000378:metabolism*; D042967:Electron Transport Complex I; D004734:Energy Metabolism; D015870:Gene Expression; D006801:Humans; D008928:Mitochondria / Q000378:metabolism*; D009247:NADH, NADPH Oxidoreductases / Q000037:antagonists & inhibitors / Q000378:metabolism; D010085:Oxidative Phosphorylation; D012559:Schizophrenia / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology*
D014150:Antipsychotic Agents; D009247:NADH, NADPH Oxidoreductases; D042967:Electron Transport Complex I; D004298:Dopamine