Abstract
Schizophrenia (SCZ) is a severe psychiatric illness with a lifetime prevalence of 0.4 %. A disturbance of energy metabolism has been suggested as part of the etiopathogenesis of the disorder. Several lines of evidence have proposed a connection between etiopathogenesis of SCZ and human brain evolution, which was characterized by an increase in the energy requirement, demanding a co-evolution of the mitochondrial system. Mitochondria are key players in brain energy homeostasis and multiple lines of evidence suggest that the system is disrupted in SCZ. In this review, we will describe the current knowledge on pathways/system involved in the human brain evolution as well as the main theories regarding the evolutionary origin of SCZ. We will furthermore discuss the role of mitochondria in the context of brain energy metabolism and its role in the etiopathogenesis of SCZ. Understanding SCZ in the context of human brain evolution opens a new perspective to elucidate pathophysiological mechanisms involved in the origin and/or portions of the complex symptomatology of this severe mental disorder.
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VFG thanks Strategic Training for Advanced Genetic Epidemiology (CIHR STAGE), University of Toronto. ACA thanks Brain & Behavior Research Foundation (Formerly NARSAD, ACA), CNPq/Brazil (GS) and Canadian Institutes of Health Research (CIHR) as sources of funding in support of this report. VFG and JLK are supported by CIHR Operating grant: Strategies for gene discovery in schizophrenia: subphenotypes, deep sequencing and interactions, MOP 115097.
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Gonçalves, V.F., Andreazza, A.C. & Kennedy, J.L. Mitochondrial dysfunction in schizophrenia: an evolutionary perspective. Hum Genet 134, 13–21 (2015). https://doi.org/10.1007/s00439-014-1491-8
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DOI: https://doi.org/10.1007/s00439-014-1491-8