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Association of Lipid Peroxidation and Brain-Derived Neurotrophic Factor with Executive Function in Adolescent Bipolar Disorder

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Abstract

Background

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.

Methods

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.

Results

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 r 2 = 0.187, F = 2.811, p = 0.035).

Conclusions

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.

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Acknowledgements

We would also like to thank the Centre for Youth Bipolar Disorder research staff, specifically those who helped with the data collection and recruitment, including Vanessa Timmins, Antonette Scavone, and Brenda Swampillai. We would also like to thank the participants and their families for their vital contributions to our research.

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Authors and Affiliations

  1. Department of Psychiatry, Sunnybrook Health Sciences Centre, 2075 Bayview Ave, Toronto, ON, M4N 3M5, Canada

    Dwight F. Newton, Melanie R. Naiberg & Benjamin I. Goldstein

  2. Department of Pharmacology and Toxicology, University of Toronto, Toronto, M5S 1A8, Canada

    Dwight F. Newton, Melanie R. Naiberg, Ana C. Andreazza, Gustavo Scola & Benjamin I. Goldstein

  3. Department of Psychiatry, University of Toronto, Toronto, M5S 1A8, Canada

    Ana C. Andreazza, Gustavo Scola & Benjamin I. Goldstein

  4. Centre for Addiction and Mental Health, Toronto, M5S 1A8, Canada

    Ana C. Andreazza & Gustavo Scola

  5. Pedi-MIND Program, Bradley Hospital, East Providence, RI, 02915, USA

    Daniel P. Dickstein

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  1. Dwight F. Newton
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  2. Melanie R. Naiberg
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  3. Ana C. Andreazza
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  4. Gustavo Scola
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Correspondence to Benjamin I. Goldstein.

Ethics declarations

These study procedures were approved by the local Research Ethics Board and are in accordance with the Helsinki Declaration of 1975.

Funding

This study was supported by an Independent Investigator Award from the Brain and Behavior Research Foundation (B. Goldstein).

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Newton, D.F., Naiberg, M.R., Andreazza, A.C. et al. Association of Lipid Peroxidation and Brain-Derived Neurotrophic Factor with Executive Function in Adolescent Bipolar Disorder. Psychopharmacology 234, 647–656 (2017). https://doi.org/10.1007/s00213-016-4500-x

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