title: Association of Lipid Peroxidation and Brain-Derived Neurotrophic Factor with Executive Function in Adolescent Bipolar Disorder.
abstract: Executive dysfunction is common and impairing in youth bipolar disorder (BD), and oxidative stress (OS) and brain-derived neurotrophic factor (BDNF) have been implicated in executive deficits of adult BD. This study aimed to determine the association between OS and executive dysfunction in BD adolescents and the influence of BDNF on this association.
  
  
  
  Serum levels of lipid hydroperoxides (LPH) and 4-hydroxy-2-nonenal (4-HNE) and BDNF levels were measured in 29 BD and 25 control adolescents. The intra-extra-dimensional (IED) set-shifting task assessed executive function. Lower IED scores indicated better performance. High and low BDNF subgroups were defined by median split.
  
  
  
  IED Z-scores were impaired in the BD group compared to controls, whereas biomarker levels were not significantly different between groups. LPH-BDNF correlations were significantly different between BD and controls (Z = 2.046, p = 0.041). In high BDNF BD subjects, LPH was significantly positively correlated with IED completed stage trials (ρ = 0.755, p = 0.001) and pre-extra-dimensional shift errors (ρ = 0.588, p = 0.017). Correlations were opposite in controls. In a linear model, LPH, BDNF, and the LPH-BDNF interaction each significantly explained variance of IED total trials (adjusted) (model r2= 0.187, F = 2.811, p = 0.035).
  
  
  
  There is a negative association between LPH and executive function in BD adolescents, which may be modulated by BDNF. LPH and BDNF may be useful biomarkers of executive function in BD. These findings highlight the importance of examining multiple peripheral biomarkers in relation to cognitive functions in BD adolescents. Future studies should explore these factors in longitudinal designs to determine the directionality of observed associations.
authors.affiliation: Department of Psychiatry, Sunnybrook Health Sciences Centre, 2075 Bayview Ave, Toronto, ON, M4N 3M5, Canada.|Department of Pharmacology and Toxicology, University of Toronto, Toronto, M5S 1A8, Canada.
authors.forename: Dwight F
authors.initials: DF
authors.lastname: Newton
authors.affiliation: Department of Psychiatry, Sunnybrook Health Sciences Centre, 2075 Bayview Ave, Toronto, ON, M4N 3M5, Canada.|Department of Pharmacology and Toxicology, University of Toronto, Toronto, M5S 1A8, Canada.
authors.forename: Melanie R
authors.initials: MR
authors.lastname: Naiberg
authors.affiliation: Department of Pharmacology and Toxicology, University of Toronto, Toronto, M5S 1A8, Canada.|Department of Psychiatry, University of Toronto, Toronto, M5S 1A8, Canada.|Centre for Addiction and Mental Health, Toronto, M5S 1A8, Canada.
authors.forename: Ana C
authors.initials: AC
authors.lastname: Andreazza
authors.affiliation: Department of Pharmacology and Toxicology, University of Toronto, Toronto, M5S 1A8, Canada.|Department of Psychiatry, University of Toronto, Toronto, M5S 1A8, Canada.|Centre for Addiction and Mental Health, Toronto, M5S 1A8, Canada.
authors.forename: Gustavo
authors.initials: G
authors.lastname: Scola
authors.affiliation: Pedi-MIND Program, Bradley Hospital, East Providence, RI, 02915, USA.
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Dickstein
authors.affiliation: Department of Psychiatry, Sunnybrook Health Sciences Centre, 2075 Bayview Ave, Toronto, ON, M4N 3M5, Canada. Benjamin.goldstein@sunnybrook.ca.|Department of Pharmacology and Toxicology, University of Toronto, Toronto, M5S 1A8, Canada. Benjamin.goldstein@sunnybrook.ca.|Department of Psychiatry, University of Toronto, Toronto, M5S 1A8, Canada. Benjamin.goldstein@sunnybrook.ca.
authors.forename: Benjamin I
authors.initials: BI
authors.lastname: Goldstein
mesh_terms: D000293:Adolescent; D000447:Aldehydes / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D001714:Bipolar Disorder / Q000097:blood* / Q000523:psychology*; D019208:Brain-Derived Neurotrophic Factor / Q000097:blood*; D003071:Cognition / Q000502:physiology; D056344:Executive Function / Q000502:physiology*; D005260:Female; D006801:Humans; D015227:Lipid Peroxidation / Q000502:physiology*; D008054:Lipid Peroxides / Q000097:blood*; D008297:Male; D018384:Oxidative Stress / Q000502:physiology; D055815:Young Adult
chemical_list: D000447:Aldehydes; D015415:Biomarkers; D019208:Brain-Derived Neurotrophic Factor; D008054:Lipid Peroxides; C579455:BDNF protein, human; C027576:4-hydroxy-2-nonenal
keywords: Bipolar disorder; Brain-derived neurotrophic factor; Child and adolescent psychiatry; Executive function; Oxidative stress