title: Regulation of leukocyte tricarboxylic acid cycle in drug-naïve Bipolar Disorder.
abstract: Several lines of evidence suggest a role for mitochondrial dysfunction in the pathophysiology of bipolar disorder (BD). The tricarboxylic acid cycle (TCA cycle) is fundamental for mitochondrial energy production and produces substrates used in oxidative phosphorylation by the mitochondrial electron transport chain. The activity of the key TCA cycle enzymes citrate synthase, malate dehydrogenase, and succinate dehydrogenase has never been evaluated in BD. In the present study, these enzymes were assayed from leukocytes of drug-naïve BD patients in a major depressive episode (n=18) and compared to 24 age-matched healthy controls. Drug-naïve BD patients did not show differences in activities of citrate synthase (p=0.79), malate dehydrogenase (p=0.17), and succinate dehydrogenase (p=0.35) compared with healthy controls. No correlation between any TCA cycle enzyme activity and severity of depressive symptoms was observed. Overall, these data suggest that the activities of the TCA cycle enzymes are not altered in major depressive episodes of recent-onset BD, which may support the concept of illness staging and neuroprogression in BD.
authors: Laboratory of Neuroscience, LIM-27, Institute and Department of Psychiatry, University of Sao Paulo, Brazil; Experimental Therapeutics and Pathophysiology Branch (ETPB), National Institute of Mental Health, NIH, Bethesda, MD, USA.
authors: Rafael T
authors: RT
authors: de Sousa
authors: Laboratory of Bioenergetics, Programa de Pós-graduação em Ciências da Saúde, Universidade do Extremo Sul Catarinense, Criciúma, SC, Brazil.
authors: Emilio L
authors: EL
authors: Streck
authors: Laboratory of Neuroscience, LIM-27, Institute and Department of Psychiatry, University of Sao Paulo, Brazil.
authors: Orestes V
authors: OV
authors: Forlenza
authors: Laboratory of Neuroscience, LIM-27, Institute and Department of Psychiatry, University of Sao Paulo, Brazil.
authors: Andre R
authors: AR
authors: Brunoni
authors: Laboratory of Neuroscience, LIM-27, Institute and Department of Psychiatry, University of Sao Paulo, Brazil; Center for Interdisciplinary Research on Applied Neurosciences (NAPNA), University of Sao Paulo, Brazil; Laboratory of Psychiatric Neuroimaging, LIM-21, Department and Institute of Psychiatry, University of Sao Paulo, Brazil.
authors: Marcus V
authors: MV
authors: Zanetti
authors: Laboratory of Bioenergetics, Programa de Pós-graduação em Ciências da Saúde, Universidade do Extremo Sul Catarinense, Criciúma, SC, Brazil.
authors: Gabriela K
authors: GK
authors: Ferreira
authors: Departament of Mental Health, Faculty of Medicine, Federal University of Minas Gerais, Belo Horizonte, Brazil; National Institute of Science and Technology-Molecular Medicine, Federal University of Minas Gerais, Belo Horizonte, Brazil.
authors: Breno S
authors: BS
authors: Diniz
authors: Department of Biochemistry, Post-Graduation Program in Biochemistry, ICBS, Federal University of Rio Grande do Sul (UFRGS), Rio Grande do Sul, Porto Alegre, Brazil.
authors: Luis V
authors: LV
authors: Portela
authors: Translational Psychiatry Research Group and Department of Clinical Medicine, Faculty of Medicine, Federal University of Ceará, Brazil.
authors: André F
authors: AF
authors: Carvalho
authors: Experimental Therapeutics and Pathophysiology Branch (ETPB), National Institute of Mental Health, NIH, Bethesda, MD, USA.
authors: Carlos A
authors: CA
authors: Zarate
authors: Laboratory of Neuroscience, LIM-27, Institute and Department of Psychiatry, University of Sao Paulo, Brazil.
authors: Wagner F
authors: WF
authors: Gattaz
authors: Laboratory of Neuroscience, LIM-27, Institute and Department of Psychiatry, University of Sao Paulo, Brazil; Laboratory of Psychiatric Neuroimaging, LIM-21, Department and Institute of Psychiatry, University of Sao Paulo, Brazil. Electronic address: machadovieirar@gmail.com.
authors: Rodrigo
authors: R
authors: Machado-Vieira
mesh_terms: D000328:Adult; D001714:Bipolar Disorder / Q000097:blood*; D016022:Case-Control Studies; D002952:Citric Acid Cycle; D005260:Female; D006801:Humans; D007962:Leukocytes / Q000378:metabolism*; D008297:Male; D055815:Young Adult
keywords: Bioenergetics; Bipolar disorder; Depression; Mitochondria; Pathophysiology; Tricarboxylic acid cycle