title: Mitochondrial activity and oxidative stress markers in peripheral blood mononuclear cells of patients with bipolar disorder, schizophrenia, and healthy subjects.
abstract: Evidence suggests that mitochondrial dysfunction is involved in the pathophysiology of psychiatric disorders such as schizophrenia (SZ) and bipolar disorder (BD). However, the exact mechanisms underlying this dysfunction are not well understood. Impaired activity of electron transport chain (ETC) complexes has been described in these disorders and may reflect changes in mitochondrial metabolism and oxidative stress markers. The objective of this study was to compare ETC complex activity and protein and lipid oxidation markers in 12 euthymic patients with BD type I, in 18 patients with stable chronic SZ, and in 30 matched healthy volunteers. Activity of complexes I, II, and III was determined by enzyme kinetics of mitochondria isolated from peripheral blood mononuclear cells (PBMCs). Protein oxidation was evaluated using the protein carbonyl content (PCC) method, and lipid peroxidation, the thiobarbituric acid reactive substances (TBARS) assay kit. A significant decrease in complex I activity was observed (p = 0.02), as well as an increase in plasma levels of TBARS (p = 0.00617) in patients with SZ when compared to matched controls. Conversely, no significant differences were found in complex I activity (p = 0.17) or in plasma TBARS levels (p = 0.26) in patients with BD vs. matched controls. Our results suggest that mitochondrial complex I dysfunction and oxidative stress play important roles in the pathophysiology of SZ and may be used in potential novel adjunctive therapy for SZ, focusing primarily on cognitive impairment and disorder progression.
authors.affiliation: Laboratório de Psiquiatria Molecular, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil. gubert.cm@gmail.com
authors.forename: Carolina
authors.initials: C
authors.lastname: Gubert
authors.forename: Laura
authors.initials: L
authors.lastname: Stertz
authors.forename: Bianca
authors.initials: B
authors.lastname: Pfaffenseller
authors.forename: Bruna Schilling
authors.initials: BS
authors.lastname: Panizzutti
authors.forename: Gislaine Tezza
authors.initials: GT
authors.lastname: Rezin
authors.forename: Raffael
authors.initials: R
authors.lastname: Massuda
authors.forename: Emilio Luiz
authors.initials: EL
authors.lastname: Streck
authors.forename: Clarissa Severino
authors.initials: CS
authors.lastname: Gama
authors.forename: Flávio
authors.initials: F
authors.lastname: Kapczinski
authors.forename: Maurício
authors.initials: M
authors.lastname: Kunz
mesh_terms: D000328:Adult; D001714:Bipolar Disorder / Q000473:pathology*; D045222:Electron Transport Chain Complex Proteins / Q000378:metabolism*; D005260:Female; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D015227:Lipid Peroxidation / Q000502:physiology; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000201:enzymology*; D018384:Oxidative Stress / Q000502:physiology*; D050050:Protein Carbonylation / Q000502:physiology; D012559:Schizophrenia / Q000473:pathology*; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
chemical_list: D045222:Electron Transport Chain Complex Proteins; D017392:Thiobarbituric Acid Reactive Substances
keywords: Bipolar disorder; Electron transport chain; Mitochondria; Oxidative stress; Schizophrenia