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Oxidative stress and immune aberrancies in attention-deficit/hyperactivity disorder (ADHD): a case–control comparison

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Abstract

The objective of this study is to compare oxidative stress and immune biomarkers between attention-deficit/hyperactivity disorder (ADHD) patients and controls without ADHD. A case–control comparison between 57 paediatric (6–12 years) untreated ADHD patients from the Antwerp University Hospital and 69 controls without ADHD from random schools in Flanders, Belgium, was conducted. Erythrocyte glutathione (GSH) and plasma lipid-soluble antioxidants (retinol, α-tocopherol, γ-tocopherol, retinyl palmitate, β-carotene, and co-enzyme Q10) were determined by HPLC with electrochemical detection, plasma malondialdehyde (MDA) by HPLC with fluorescence detection, plasma cytokines (interleukin (IL)-1β, IL-5, IL-6, IL-8, IL-10, tumour necrosis factor (TNF) and interferon (INF)-γ) and immunoglobulins (IgE, IgG and IgM) by flow cytometry and urinary 8-hydroxy-2′deoxyguanosine (8-OHdG) levels by ELISA assay. Dietary habits were determined by a food frequency questionnaire. Plasma MDA levels were on average 0.031 µM higher in patients than in controls (p < 0.05), and a trend for higher urinary 8-OHdG was observed. Erythrocyte GSH and plasma retinyl palmitate levels, as well as IgG and IgE levels, were higher in patients than in controls as well (on average 93.707 µg/ml, 0.006 µg/ml, 301.555 µg/ml and 125.004 µg/ml, resp., p < 0.05). Finally, a trend for lower plasma IL-5 levels was observed. After Bonferroni correction for multiple testing, the difference in GSH levels remained statistically significant (nominally significant for retinyl palmitate), while significance was lost for MDA, IgG and IgE levels. Dietary habits do not appear to cause the observed differences. These results point at the potential involvement of slight oxidative stress and immune disturbances in ADHD.

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Acknowledgements

The Fund for Scientific research (FWO Flanders, Belgium) is acknowledged for the financial support (FWO MAND 2013-11U8314 N). FWO had no role in the study design; the collection, analysis and interpretation of data; writing of the report; and the decision to submit the article for publication. The authors would like to thank Dr. J. Ruinemans-Koerts (Clinical Chemical and Haematological Laboratory, Rijnstate Hospital, Wagnerlaan 55, 6815 AD Arnhem, The Netherlands) for her help with the antibody analyses.

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  1. Natural Products and Food Research & Analysis (NatuRA), Department of Pharmaceutical Sciences, University of Antwerp, Annelies Verlaet, Universiteitsplein 1, 2610, Wilrijk, Belgium

    Annelies A. J. Verlaet, Annelies Breynaert, Tess De Bruyne, Luc Pieters & Nina Hermans

  2. Paediatric Neurology, University Hospital Antwerp, Wilrijkstraat 10, 2650, Edegem, Belgium

    Berten Ceulemans

  3. STATUA, University of Antwerp, Prins Boudewijnlaan 43, 2650, Edegem, Belgium

    Erik Fransen

  4. Cell Biology and Immunology Group, Wageningen University, P.O. Box 338, 6708 WD, Wageningen, The Netherlands

    Huub F. J. Savelkoul

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  1. Annelies A. J. Verlaet
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Verlaet, A.A.J., Breynaert, A., Ceulemans, B. et al. Oxidative stress and immune aberrancies in attention-deficit/hyperactivity disorder (ADHD): a case–control comparison. Eur Child Adolesc Psychiatry 28, 719–729 (2019). https://doi.org/10.1007/s00787-018-1239-4

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