title: Peripheral markers of oxidative stress and antioxidative defense in euthymia of bipolar disorder--Gender and obesity effects.
abstract: BACKGROUND
  Oxidative and nitrosative stress are implicated in the pathogenesis of uni- and bipolar disorder. Herein we primarily sought to characterize markers of oxidative/nitrosative stress during euthymia in adults with bipolar disorder (BD). Oxidative markers were further evaluated in this BD sample in synopsis with excess overweight or obesity and/or comorbid metabolic syndrome (MetS).
  
  
  METHODS
  Peripheral markers of oxidative stress [i.e. thiobarbituric acid reactive substance, (TBARS), malondialdehyde (MDA), and carbonyl proteins] and antioxidant markers [e.g. total antioxidative capacity (TAC), superoxide dismutase (SOD), glutathione S-transferase (GST)] were obtained in a cohort of euthymic adults with BD (N=113) and compared to healthy controls (CG) (N=78). Additionally, anthropometric measures included the body mass index (BMI) [kg/m(2)], waist and hip circumference [cm], waist-to-hip-ratio (WHR), waist to height ratio (WtHR) as well as the IDF-defined MetS.
  
  
  RESULTS
  The major finding was a significantly decreased TAC in BD compared to the CG (p<0.01; BD: M 1.18, SD 0.47; CG: M 1.39, SD 0.49). MDA was significantly and TBARS by trend higher in the CG compared to the euthymic bipolar test persons (MDA: p<0.01, BD: M 0.70, SD 0.18; CG: M 0.81, SD 0.25; TBARS: p<0.1, BD: M 0.78, SD 0.28; CG: M 0.76, SD 0.30). The antioxidative enzyme GST was significantly elevated in both patients and controls (BD: M 298.24, SD 133.02; CG: M 307.27 SD 118.18). Subgroup analysis revealed that the CG with concurrent MetS and obesity had significantly elevated TAC when compared to CG without concurrent MetS (p<0.05, no MetS: M 1.33, SD 0.50; MetS: M 1.67, SD 0.32), as well as persons with BD with or without current MetS (no MetS: M 1.18, SD 0.44; MetS: M 1.15, SD 0.49). Significant correlations between GST and anthropometric variables were found in male study participants. Multivariate analysis indicated a significant gender effect concerning TBARS values in all patients and CG (p<0.01, females: M 0.73, SD 0.29; males: M 0.83, SD 0.28).
  
  
  CONCLUSIONS
  Euthymic bipolar adults exhibit peripheral evidence of a disturbed biosignature of oxidative stress and antioxidative defense. Male test persons showed significantly higher peripheral markers of oxidative stress than women- female sex may exert protective effects. Furthermore, the biosignature of oxidative stress obtained herein was more pronounced in males with concurrent metabolic disorders. Our results further extend knowledge by introducing the moderating influence of gender and obesity on oxidative stress and BD.
authors.affiliation: Medical University of Graz, Department of Psychiatry, Graz, Austria.
authors.forename: S A
authors.initials: SA
authors.lastname: Bengesser
authors.affiliation: Medical University of Graz, Department of Psychiatry, Graz, Austria. Electronic address: Nina.Lackner@medunigraz.at.
authors.forename: N
authors.initials: N
authors.lastname: Lackner
authors.affiliation: Medical University of Graz, Department of Psychiatry, Graz, Austria.
authors.forename: A
authors.initials: A
authors.lastname: Birner
authors.affiliation: Medical University of Graz, Department of Psychiatry, Graz, Austria.
authors.forename: F T
authors.initials: FT
authors.lastname: Fellendorf
authors.affiliation: Medical University of Graz, Department of Psychiatry, Graz, Austria.
authors.forename: M
authors.initials: M
authors.lastname: Platzer
authors.affiliation: Medical University of Graz, Department of Psychiatry, Graz, Austria.
authors.forename: A
authors.initials: A
authors.lastname: Mitteregger
authors.affiliation: Medical University of Graz, Department of Psychiatry, Graz, Austria.
authors.forename: R
authors.initials: R
authors.lastname: Unterweger
authors.affiliation: Medical University of Graz, Department of Psychiatry, Graz, Austria; Therapiezentrum Justuspark, Linzer Straße 7, 4540 Bad Hall, Austria.
authors.forename: B
authors.initials: B
authors.lastname: Reininghaus
authors.affiliation: Clinical Institute of Medical and Chemical Laboratory Diagnostics, Graz, Austria.
authors.forename: H
authors.initials: H
authors.lastname: Mangge
authors.affiliation: Institute of Pathophysiology and Immunology, Graz, Austria.
authors.forename: S J
authors.initials: SJ
authors.lastname: Wallner-Liebmann
authors.affiliation: Clinical Institute of Medical and Chemical Laboratory Diagnostics, Graz, Austria.
authors.forename: S
authors.initials: S
authors.lastname: Zelzer
authors.affiliation: Medical University of Innsbruck, Biocenter, Division of Biological Chemistry, Innsbruck, Austria.
authors.forename: D
authors.initials: D
authors.lastname: Fuchs
authors.affiliation: University of Toronto, Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, ON, Canada.
authors.forename: R S
authors.initials: RS
authors.lastname: McIntyre
authors.affiliation: Medical University of Graz, Department of Psychiatry, Graz, Austria.
authors.forename: H P
authors.initials: HP
authors.lastname: Kapfhammer
authors.affiliation: Medical University of Graz, Department of Psychiatry, Graz, Austria.
authors.forename: E Z
authors.initials: EZ
authors.lastname: Reininghaus
mesh_terms: D000328:Adult; D000975:Antioxidants / Q000378:metabolism*; D015415:Biomarkers / Q000097:blood*; D001714:Bipolar Disorder / Q000097:blood* / Q000378:metabolism; D015992:Body Mass Index; D003527:Cyclothymic Disorder / Q000097:blood* / Q000378:metabolism; D005260:Female; D005982:Glutathione Transferase / Q000097:blood; D006801:Humans; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D024821:Metabolic Syndrome / Q000097:blood; D008875:Middle Aged; D009765:Obesity / Q000097:blood* / Q000378:metabolism; D050177:Overweight / Q000097:blood; D018384:Oxidative Stress; D012737:Sex Factors; D013482:Superoxide Dismutase / Q000097:blood; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D049629:Waist-Hip Ratio
chemical_list: D000975:Antioxidants; D015415:Biomarkers; D017392:Thiobarbituric Acid Reactive Substances; D008315:Malondialdehyde; D013482:Superoxide Dismutase; D005982:Glutathione Transferase
keywords: Antioxidants; Bipolar disorder; Glutathione S-transferase; Malondialdehyde; Oxidative stress; Total antioxidative capacity