title: Mitochondrial dysfunction in bipolar disorder: Evidence, pathophysiology and translational implications.
abstract: Bipolar disorder (BD) is a chronic psychiatric illness characterized by severe and biphasic changes in mood. Several pathophysiological mechanisms have been hypothesized to underpin the neurobiology of BD, including the presence of mitochondrial dysfunction. A confluence of evidence points to an underlying dysfunction of mitochondria, including decreases in mitochondrial respiration, high-energy phosphates and pH; changes in mitochondrial morphology; increases in mitochondrial DNA polymorphisms; and downregulation of nuclear mRNA molecules and proteins involved in mitochondrial respiration. Mitochondria play a pivotal role in neuronal cell survival or death as regulators of both energy metabolism and cell survival and death pathways. Thus, in this review, we discuss the genetic and physiological components of mitochondria and the evidence for mitochondrial abnormalities in BD. The final part of this review discusses mitochondria as a potential target of therapeutic interventions in BD.
authors.affiliation: Translational Psychiatry Program, Department of Psychiatry and Behavioral Sciences, McGovern Medical School, The University of Texas Health Science Center at Houston (UTHealth), Houston, TX, USA; Laboratory of Bioenergetics, Graduate Program in Health Sciences, Health Sciences Unit, Universidade do Extremo Sul Catarinense, Criciúma, SC, Brazil.
authors.forename: Giselli
authors.initials: G
authors.lastname: Scaini
authors.affiliation: Laboratory of Clinical and Experimental Pathophysiology, Graduate Program in Health Sciences, Universidade do Sul de Santa Catarina, Tubarão, SC, Brazil.
authors.forename: Gislaine T
authors.initials: GT
authors.lastname: Rezin
authors.affiliation: Translational Psychiatry Research Group and Department of Clinical Medicine, Faculty of Medicine, Federal University of Ceara, Fortaleza, CE, Brazil.
authors.forename: Andre F
authors.initials: AF
authors.lastname: Carvalho
authors.affiliation: Laboratory of Bioenergetics, Graduate Program in Health Sciences, Health Sciences Unit, Universidade do Extremo Sul Catarinense, Criciúma, SC, Brazil.
authors.forename: Emilio L
authors.initials: EL
authors.lastname: Streck
authors.affiliation: Deakin University, IMPACT Strategic Research Centre, School of Medicine, Faculty of Health, Geelong, Victoria, Australia; Orygen, The National Centre of Excellence in Youth Mental Health and The Centre for Youth Mental Health, The Department of Psychiatry and The Florey Institute for Neuroscience and Mental Health, The University of Melbourne, Parkville, Australia.
authors.forename: Michael
authors.initials: M
authors.lastname: Berk
authors.affiliation: Translational Psychiatry Program, Department of Psychiatry and Behavioral Sciences, McGovern Medical School, The University of Texas Health Science Center at Houston (UTHealth), Houston, TX, USA; Center of Excellence on Mood Disorders, Department of Psychiatry and Behavioral Sciences, McGovern Medical School, The University of Texas Health Science Center at Houston (UTHealth), Houston, TX, USA; Neuroscience Graduate Program, The University of Texas Graduate School of Biomedical Sciences at Houston, Houston, TX, USA; Laboratory of Neurosciences, Graduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina (UNESC), Criciúma, SC, Brazil. Electronic address: Joao.L.DeQuevedo@uth.tmc.edu.
authors.forename: João
authors.initials: J
authors.lastname: Quevedo
mesh_terms: D001714:Bipolar Disorder; D004734:Energy Metabolism; D008928:Mitochondria; D011110:Polymorphism, Genetic
keywords: Apoptosis; Bipolar disorder; Depression; Inflammation; Mania; Mitochondria; Mitochondrial dysfunction; Neurogenesis; Oxidative stress