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European Child & Adolescent Psychiatry

, Volume 28, Issue 5, pp 719–729 | Cite as

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

  • Annelies A. J. VerlaetEmail author
  • Annelies Breynaert
  • Berten Ceulemans
  • Tess De Bruyne
  • Erik Fransen
  • Luc Pieters
  • Huub F. J. Savelkoul
  • Nina Hermans
Original Contribution

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.

Keywords

ADHD Oxidative stress Antioxidants Immunity Diet 

Notes

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.

Compliance with ethical standard

Conflict of interest

The authors declare that they have no conflict of interest.

References

  1. 1.
    APA (2013) American Psychiatric Association: DSM-5 attention deficit/hyperactivity disorder fact sheet. http://www.dsm5.org/Documents/ADHD%20Fact%20Sheet.pdf. Accessed 8 Feb 2018
  2. 2.
    APA (2000) American psychiatric association: diagnostic and statistical manual of mental disorders, 4th edn. Text Revision, WashingtonGoogle Scholar
  3. 3.
    Polanczyk G, de Lima MS, Horta BL, Biederman J, Rohde LA (2007) The Worldwide Prevalence of ADHD: a systematic review and metaregression analysis. Am J Psychiatry 164:942–948CrossRefGoogle Scholar
  4. 4.
    Bope E, Kellerman D (2013) Attention-deficit/hyperactivity disorder. Conn’s current therapy [Internet]. Elsevier, Philadelphia, pp 1050–1053Google Scholar
  5. 5.
    Biederman J, Faraone SV (2005) Attention-deficit hyperactivity disorder. Lancet 366:237–248CrossRefGoogle Scholar
  6. 6.
    Thapar A, Martin J, Mick E, Arias Vásquez A, Langley K, Scherer SW et al (2016) Psychiatric gene discoveries shape evidence on ADHD’s biology. Mol Psychiatry 21:1202–1207CrossRefGoogle Scholar
  7. 7.
    Demontis D, Walters RK, Martin J, Mattheisen M, Damm Als T, Agerbo E, et al. (2018) Discovery of the first genome-wide significant risk loci for ADHD. Nat Genet.  https://doi.org/10.1101/145581
  8. 8.
    Verlaet AAJ, Maasakkers CM, Hermans N, Savelkoul HFJ (2018) Rationale for dietary antioxidant treatment of ADHD. Nutrients 10:405–424CrossRefGoogle Scholar
  9. 9.
    Ng F, Berk M, Dean O, Bush AI (2008) Oxidative stress in psychiatric disorders: evidence base and therapeutic implications. Int J Neuropsychopharmacol 11:851–876CrossRefGoogle Scholar
  10. 10.
    Ceylan M, Senerb S, Bayraktarc AC, Kavutcuc M (2010) Oxidative imbalance in child and adolescent patients with attention-deficit/hyperactivity disorder. Prog Neuropsychopharmacol Biol Psychiatry 34:1491–1494CrossRefGoogle Scholar
  11. 11.
    Ross BM, McKenzie I, Glen I, Bennett CP (2003) Increased levels of ethane, a non-invasive marker of n − 3 fatty acid oxidation, in breath of children with attention deficit hyperactivity disorder. Nutr Neurosci 6:277–281CrossRefGoogle Scholar
  12. 12.
    Kawatani M, Tsukahara H, Mayumi M (2011) Evaluation of oxidative stress status in children with pervasive developmental disorder and attention deficit hyperactivity disorder using urinary-specific biomarkers. Redox Rep 16:45–46CrossRefGoogle Scholar
  13. 13.
    Güngör S, Celiloğlu O, Ozcan O, Raif S, Selimoğlu M (2013) The frequency of celiac disease in attention-deficit hyperactivity disorder. J Pediatr Gastroenterol Nutr 56:211–214CrossRefGoogle Scholar
  14. 14.
    Minter K, Roberts J, Hooper S, Burchinal M, Zeisel S (2001) Early childhood otitis media in relation to children’s attention-related behavior in the first six years of life. Pediatrics 107:1037–1042CrossRefGoogle Scholar
  15. 15.
    Pelsser LMJ, Buitelaar JK, Savelkoul HFJ (2009) ADHD as a (non) allergic hypersensitivity disorder: a hypothesis. Pediatr Allergy Immunol 20:107–112CrossRefGoogle Scholar
  16. 16.
    Schmitt J, Buske-Kirschbaum A, Roessner V (2010) Is atopic disease a risk factor for attention-deficit/hyperactivity disorder? A systematic review. Allergy 65:1506–1524CrossRefGoogle Scholar
  17. 17.
    Tsai SJ (2006) Signal transducer and activator of transcription 6 (STAT6) and attention-deficit hyperactivity disorder: a speculative hypothesis. Med Hypotheses 67:1341–1343Google Scholar
  18. 18.
    Ceylan M, Sener S, Bayraktar A, Kavutcu M (2012) Changes in oxidative stress and cellular immunity serum markers in attention-deficit/hyperactivity disorder. Psychiatry Clin Neurosci 66:220–226CrossRefGoogle Scholar
  19. 19.
    Hess JL, Akutagava-Martins GC, Patak JD, Glatt SJ, Faraone SV (2017) Why is there selective subcortical vulnerability in ADHD? Clues from postmortem brain gene expression data. Mol Psychiatry.  https://doi.org/10.1038/mp.2017.242
  20. 20.
    Bulut M, Selek S, Gergerlioglu HS, Savas HA, Yilmaz HR, Yuce M et al (2007) Malondialdehyde levels in adult attention-deficit hyperactivity disorder. J Psychiatry Neurosci 32:435–438Google Scholar
  21. 21.
    Kerschensteiner M, Meinl E, Hohlfeld R (2009) Neuro-immune crosstalk in CNS diseases. Neuroscience 158:1122–1132CrossRefGoogle Scholar
  22. 22.
    Chovanová Z, Muchová J, Sivoňová M, Dvoráková M, Zitnanová I, Waczulíková I et al (2006) Effect of polyphenolic extract, Pycnogenol, on the level of 8-oxoguanine in children suffering from attention deficit/hyperactivity disorder. Free Radical Res 40:1003–1010CrossRefGoogle Scholar
  23. 23.
    Spahis S, Vanasse M, Bélanger SA, Ghadirian P, Grenier E, Levy E (2008) Lipid profile, fatty acid composition and pro- and anti-oxidant status in pediatric patients with attention-deficit/hyperactivity disorder. Prostaglandins Leukot Essent Fatty Acids 79:47–53CrossRefGoogle Scholar
  24. 24.
    Oztop D, Altun H, Baskol G, Ozsoy S (2012) Oxidative stress in children with attention deficit hyperactivity disorder. Clin Biochem 45:745–748CrossRefGoogle Scholar
  25. 25.
    TestWeb (2013) Sociaal-Emotionele Vragenlijst (SEV): Bohn Stafleu van Loghum. Springer. http://testweb.bsl.nl/tests/sev/
  26. 26.
    Jeunen E (2011) Onderzoek naar voedingsproblemen bij preterm geboren kleuters. Katholieke Hogeschool Kempen (Ed), Geel, BelgiumGoogle Scholar
  27. 27.
    Magielse J (2013) Investigation of the biological activity of plant food supplements in animal models: evaluation of the antioxidant efficacy of Cynara scolymus and the hepatoprotective activity of Desmodium adscendens. University of Antwerp, AntwerpGoogle Scholar
  28. 28.
    Magielse J, Verlaet A, Breynaert A, Manuel YKB, Apers S, Pieters L et al (2014) Investigation of the in vivo antioxidative activity of Cynara scolymus (artichoke) leaf in the streptozotocin-induced diabetic rat. Mol Nutr Food Res 58:211–215CrossRefGoogle Scholar
  29. 29.
    Conaway HH, Henning P, Lerner UH (2013) Vitamin a metabolism, action, and role in skeletal homeostasis. Endocrine Rev 34:766–797CrossRefGoogle Scholar
  30. 30.
    Naguib Y, Hari SP, Passwater R Jr, Huang D (2003) Antioxidant activities of natural vitamin E formulations. J Nutr Sci Vitaminol 49:217–220CrossRefGoogle Scholar
  31. 31.
    Littarru GP, Tiano L (2007) Bioenergetic and antioxidant properties of coenzyme Q10: recent developments. Mol Biotechnol 37:31–37CrossRefGoogle Scholar
  32. 32.
    Molyneux SL, Young JM, Florkowski CM, Lever M, George PM (2008) Coenzyme Q10: is there a clinical role and a case for measurement? Clin Biochem Rev 29:71–82Google Scholar
  33. 33.
    Hermans N, Cos P, Vanden Berghe D, Vlietinck A, De Bruyne T (2005) Method development and validation for monitoring in vivo oxidative stress: evaluation of lipid peroxidation and fat-soluble vitamin status by HPLC in rat plasma. J Chromatogr B 822:33–39CrossRefGoogle Scholar
  34. 34.
    Aruoma OI (1998) Free radicals, oxidative stress, and antioxidants in human health and disease. JAOCS 75:199–212CrossRefGoogle Scholar
  35. 35.
    Yano T, Shoji F, Baba H, Koga T, Shiraishi T, Orita H, Kohno H (2009) Significance of the urinary 8-OHdG level as an oxidative stress marker in lung cancer patients. Lung Cancer 63:111–114CrossRefGoogle Scholar
  36. 36.
    Wu LL, Chang P, Wu JT (2004) Urinary 8-OHdG: a marker of oxidative stress to DNA and a risk factor for cancer, atherosclerosis and diabetics. Clin Chim Acta 339:1–9CrossRefGoogle Scholar
  37. 37.
    Dandona P, Ghanim H, Chaudhuri A, Dhindsa S, Kim SS (2010) Macronutrient intake induces oxidative and inflammatory stress: potential relevance to atherosclerosis and insulin resistance. Exp Mol Med 42:245–253CrossRefGoogle Scholar
  38. 38.
    Folchetti LD, Monfort-Pires M, de Barros CR, Martini LA, Ferreira SRG (2014) Association of fruits and vegetables consumption and related-vitamins with inflammatory and oxidative stress markers in prediabetic individuals. Diabetol Metab Syndr 6:22–29CrossRefGoogle Scholar
  39. 39.
    Fismen AS, Smith ORF, Torsheim T, Rasmussen M, Pedersen Pagh T, Augustine L, Ojala K, Samdal O (2016) Trends in food habits and their relation to socioeconomic status among Nordic adolescents 2001/2002-2009/2010. PLoS ONE 11:e0148541CrossRefGoogle Scholar
  40. 40.
    Ramakrishnan U, Imhoff-Kunsch B, DiGirolamo AM (2009) Role of docosahexaenoic acid in maternal and child mental health. Am J Clin Nutr 89:958S–962SCrossRefGoogle Scholar
  41. 41.
    Gillies D, Sinn JKH, Lad SS, Leach MJ, Ross MJ (2012) Polyunsaturated fatty acids (PUFA) for attention deficit hyperactivity disorder (ADHD) in children and adolescents. Cochrane Database Syst Rev 11(7):CD007986.  https://doi.org/10.1002/14651858.CD007986.pub2
  42. 42.
    Sinn N (2008) Nutritional and dietary influences on attention deficit hyperactivity disorder. Nutr Rev 66:558–568CrossRefGoogle Scholar
  43. 43.
    Hurt EA, Arnold LE, Lofthouse N (2011) Dietary and nutritional treatments for attention-deficit/hyperactivity disorder: current research support and recommendations for practitioners. Curr Psychiatry Rep 13:323–332CrossRefGoogle Scholar
  44. 44.
    Hawkey E, Nigg JT (2014) Omega-3 fatty acid and ADHD: blood level analysis and meta-analytic extension of supplementation trials. Clin Psychol Rev 34:496–505CrossRefGoogle Scholar
  45. 45.
    Bos DJ, Oranje B, Veerhoek ES, van Diepen RM, Weusten JMH, Demmelmair H, Koletzko B, de Sain-van der Velden MG, Eilander A, Hoeksma M, Durston S (2015) Reduced symptoms of inattention after dietary omega-3 fatty acid supplementation in boys with and without attention deficit/hyperactivity disorder. Neuropshychopharmacology 40:2298–2306CrossRefGoogle Scholar
  46. 46.
    Ortega RM, Rodriguez-Rodriguez E, Lopez-Sobaler AM (2012) Effects of omega-3 fatty acids supplementation in behaviour and non-neurodegenerative neuropsychiatric disorders. Br J Nutr 107:S261–S270CrossRefGoogle Scholar
  47. 47.
    Grassmann V, Santos-Galduroz RF, Galduroz SCF (2013) Effects of low doses of polyunsaturated fatty acids on the attention deficit/hyperactivity disorder of children: a systematic review. Curr Neuropharmacol 11:186–196CrossRefGoogle Scholar
  48. 48.
    Schuchardt JP, Huss M, Stauss-Grabo M, Hahn A (2010) Significance of long-chain polyunsaturated fatty acids (PUFAs) for the development and behaviour of children. Eur J Pediatr 169:149–164CrossRefGoogle Scholar
  49. 49.
    Puri BK, Martins JG (2014) Which polyunsaturated fatty acids are active in children with attention-deficit hyperactivity disorder receiving PUFA supplementation? A fatty acid validated meta-regression analysis of randomized controlled trials. Prostagland Leukotr Essent Fatty Acids 90:179–189CrossRefGoogle Scholar
  50. 50.
    Bos DJ, van Montfort SJT, Oranje B, Durston S, Smeets PAM (2016) Effects of omega-3 polyunsaturated fatty acids on human brain morphology and function: What is the evidence? Eur Neuropsychopharmacol 26:546–561CrossRefGoogle Scholar
  51. 51.
    Millichap JG, Yee MM (2012) The diet factor in attention-deficit/hyperactivity disorder. Pediatrics 129:330–337CrossRefGoogle Scholar
  52. 52.
    Skokauskas N, McNicholas F, Masaud T, Frodl T (2011) Complementary medicine for children and young people who have attention deficit hyperactivity disorder. Curr Opin Psychiatry 24:291–300CrossRefGoogle Scholar
  53. 53.
    Matsudaira T, Gow RV, Kelly J, Murphy C, Potts L, Sumich A, Ghebremeskel K, Crawford MA, Taylor E (2015) Biochemical and psychological effects of omega-3/6 supplements in male adolescents with attention-deficit/hyperactivity disorder: a randomized, placebo-controlled, clinical trial. J Child Adol Psychopharmacol 25:775–782CrossRefGoogle Scholar
  54. 54.
    Transler C, Eilander A, Mitchell S, van de Meer N (2010) The impact of polyunsaturated fatty acids in reducing child attention deficit and hyperactivity disorders. J Atten Disord 14:232–246CrossRefGoogle Scholar
  55. 55.
    Königs A, Kiliaan AJ (2016) Critical appraisal of omega-3 fatty acids in attention-deficit/hyperactivity disorder treatment. Neuropsychiatr Dis Treat 12:1869–1882CrossRefGoogle Scholar
  56. 56.
    Joshi K, Lad S, Kale M, Patwardhan B, Mahadik SP, Patni B, Chaudhary A, Bhave S, Pandit A (2006) Supplementation with flax oil and vitamin C improves the outcome of attention deficit hyperactivity disorder (ADHD). Prostagland Leukot Essent Fatty Acids 74:17–21CrossRefGoogle Scholar
  57. 57.
    Dvořáková M, Sivoňová M, Trebatická J, Skodácek I, Waczuliková I, Muchová J, Duracková Z (2006) The effect of polyphenolic extract from pine bark, Pycnogenol, on the level of glutathione in children suffering from attention deficit hyperactivity disorder (ADHD). Redox Rep 11:163–172CrossRefGoogle Scholar
  58. 58.
    Pravkin SK, Yakusheva EN, Uzbekova DG (2013) In vivo analysis of antioxidant and prooxidant properties of retinol acetate. Bull Exp Biol Med 156:220–223CrossRefGoogle Scholar
  59. 59.
    De Oliveira MR (2015) The neurotoxic effects of vitamin A and retinoids. Ann Brazl Acad Sci 87:1361–1373CrossRefGoogle Scholar
  60. 60.
    Ciaccio M, Valenza M, Tesoriere L, Bongiorno A, Albiero R, Livrea MA (1993) Vitamin A inhibits doxorubicin-induced membrane lipid peroxidation in rat tissues in vivo. Arch Biochem Biophys 302:103–108CrossRefGoogle Scholar
  61. 61.
    Schwarz KB, Cox JM, Sharma S, Clement L, Humphrey J, Gleason C, Abbey H, Sehnert SS, Risby TH (1997) Possible antioxidant effect of vitamin A supplementation in premature infants. J Pediatr Gastroenterol Nutr 24:408–414CrossRefGoogle Scholar
  62. 62.
    Petiz LL, Girardi CS, Bortolin RC, Kunzler A, Gasparotto J, Rabelo TK, Matté C, Moreira JCF, Gelain DP (2017) Vitamin A oral supplementation induces oxidative stress and suppresses IL-10 and HSP70 in skeletal muscle of trained rats. Nutrients 9:353CrossRefGoogle Scholar
  63. 63.
    Olson JA (1993) Vitamin A and carotenoids as antioxidants in a physiological context. J Nutr Sci Vitamol 39:S57–S65CrossRefGoogle Scholar
  64. 64.
    Landaas ET, Aarsland TIM, Ulvik A, Halmøy A, Ueland PM, Haavik J (2016) Vitamin levels in adults with ADHD. BJPsych Open 2:337–384CrossRefGoogle Scholar
  65. 65.
    Çelik K, Erşan E, Erşan S, Bakır S, Dogan O (2013) Plasma catalase, glutathione-s-transferase and total antioxidant activity levels of children with attention deficit and hyperactivity disorder. Adv Biosci Biotechnol 4:183–187CrossRefGoogle Scholar
  66. 66.
    Ruchi K, Anil Kumar S, Sunil G, Bashir A, Prabhat S (2011) Antioxidant activity in children with ADHD—a comparison in untreated and treated subjects with normal children. Int Med J Malaysia 10:31–35Google Scholar
  67. 67.
    Russo AJ (2010) Decreased serum Cu/Zn SOD associated with high copper in children with attention deficit hyperactivity disorder (ADHD). J Central Nervous System Dis 2:9–14Google Scholar
  68. 68.
    Kul M, Unal F, Kandemir H, Sarkarati B, Kilinc K, Kandemir SB (2015) Evaluation of oxidative metabolism in child and adolescent patients with attention deficit hyperactivity disorder. Psychiatry Investig 12:361–366CrossRefGoogle Scholar
  69. 69.
    Sezen H, Kandemir H, Savik E, Basmacı Kandemir S, Kilicaslan F, Bilinc H, Aksoy N (2016) Increased oxidative stress in children with attention deficit hyperactivity disorder. Redox Rep 21:248–253CrossRefGoogle Scholar
  70. 70.
    Guney E, Cetin FH, Alisik M, Tunca H, Torun YT, Iseri E, Taner YI, Cayci B, Erel O (2015) Attention deficit hyperactivity disorder and oxidative stress: a short term follow up study. Psychiatry Res 229:310–317CrossRefGoogle Scholar
  71. 71.
    Joseph N, Zhang-James Y, Perl A, Faraone SV (2015) Oxidative stress and ADHD: a meta-analysis. J Atten Disord 19:915–924CrossRefGoogle Scholar
  72. 72.
    Sasayama D, Kurahashi K, Oda K, Yasaki T, Yamada Y, Sugiyama N, Inaba Y, Harada Y, Washizuka S, Honda H (2017) Negative correlation between serum cytokine levels and cognitive abilities in children with autism spectrum disorder. J Intell 5:19–26CrossRefGoogle Scholar
  73. 73.
    Lopresti AL (2015) Oxidative and nitrosative stress in ADHD: possible causes and the potential of antioxidant-targeted therapies. ADHD 7:237–247Google Scholar
  74. 74.
    Delion S, Chalon S, Hérault J, Guilloteau D, Besnard J-C, Durand G (1994) Chronic dietary a-linolenic acid deficiency alters dopaminergic and serotoninergic neurotransmission in rats. J Nutr 124:2466–2476CrossRefGoogle Scholar
  75. 75.
    King MR, Ismail AS, Davis LS, Karp DR (2006) Oxidative stress promotes polarisation of human T cell differentiation toward a T helper 2 phenotype. J Immunol 176:2765–2772CrossRefGoogle Scholar
  76. 76.
    Dröge W, Breitkreutz R (2000) Glutathione and immune function. Proc Nutr Soc 59:595–600CrossRefGoogle Scholar
  77. 77.
    Furukawa T, Meydani SN, Blumberg JB (1987) Reversal of age-associated decline in immune responsiveness by dietary glutathione supplementation in mice. Mech Ageing Dev 38:107–117CrossRefGoogle Scholar
  78. 78.
    Vaziri ND (2008) Causal link between oxidative stress, inflammation, and hypertension. IJKD 2:1–10Google Scholar
  79. 79.
    Martins T, Bandhauer ME, Bunker AM, Roberts WL, Hill HR (2014) New childhood and adult reference intervals for total IgE. J Allergy Clin Immunol 133:589–591CrossRefGoogle Scholar
  80. 80.
    Bernstein IL, Li JT, Bernstein DI, Hamilton R, Spector SL, Tan R et al (2008) Allergy diagnostic testing: an updated practice parameter. Ann Allergy Asthma Immunol 100:S1–S148CrossRefGoogle Scholar
  81. 81.
    Dugernier TL, Laterre PF, Wittebole X, Roeseler J, Latinne D, Reynaert MS et al (2003) Compartmentalization of the inflammatory response during acute pancreatitis correlation with local and systemic complications. Am J Respir Crit Care Med 168:148–157CrossRefGoogle Scholar
  82. 82.
    Mallone R, Mannering SI, Brooks-Worrell BM, Durinovic-Belló I, Cilio CM, Wong FS et al (2010) Isolation and preservation of peripheral blood mononuclear cells for analysis of islet antigen-reactive T cell responses: position statement of the T-Cell Workshop Committee of the Immunology of Diabetes Society. Clin Exp Immunol 163:33–49CrossRefGoogle Scholar
  83. 83.
    Singer RE, Moss K, Beck JD, Offenbacher S (2009) Association of systemic oxidative stress with suppressed serum IgG to commensal oral biofilm and modulation by periodontal infection. Antioxid Redox Signal 11:2973–2983CrossRefGoogle Scholar
  84. 84.
    Abbas AK, Lichtman AH, Pillai S (2015) Cellular and molecular immunology. Elsevier Saunders, PhiladelphiaGoogle Scholar
  85. 85.
    Chen M, Su T, Chen Y, Hsu J, Huang K, Chang W et al (2013) Attention deficit hyperactivity disorder, tic disorder, and allergy: is there a link? A nationwide population-based study. J Child Psychol Psychiatry 54:545–551CrossRefGoogle Scholar
  86. 86.
    Pelsser LMJ, Frankena K, Toorman J, Savelkoul HFJ, Dubois AE, Pereira RR et al (2011) Effects of a restricted elimination diet on the behaviour of children with attention-deficit hyperactivity disorder (INCA study): a randomised controlled trial. Lancet 377:494–503CrossRefGoogle Scholar
  87. 87.
    Gaitens T, Kaplan BJ, Freigang B (1998) Absence of an association between IgE-mediated atopic responsiveness and ADHD symptomatology. J Child Psychol Psychiatry 39:427–431CrossRefGoogle Scholar
  88. 88.
    McGee R, Stanton WR, Sears MR (1993) Allergic disorders and attention deficit disorder in children. J Abnorm Child Psychol 21:79–88CrossRefGoogle Scholar
  89. 89.
    Blank R, Remschmidt H (1994) Hyperkinetic syndrome: the role of allergy among psychological and neurological factors. Eur Child Adol Psychiatry 3:220–228CrossRefGoogle Scholar
  90. 90.
    Mittleman BB, Castellanos FX, Jacobsen LK, Rapoport JL, Swedo SE, Shearer GM (1997) cerebrospinal fluid cytokines in pediatric neuropsychiatric disease. J Immunol 159:2994–2999Google Scholar
  91. 91.
    Oades RD, Dauvermann MR, Schimmelmann BG, Schwarz MJ, Myint A-M (2010) Attention-deficit hyperactivity disorder (ADHD) and glial integrity: S100B, cytokines and kynurenine metabolism—effects of medication. Behav Brain Funct 6:2–14CrossRefGoogle Scholar
  92. 92.
    Buske-Kirschbaum A, Schmitt J, Plessowa F, Romanos M, Weidinger S, Roessner V (2013) Psychoendocrine and psychoneuroimmunological mechanisms in the comorbidity of atopic eczema and attention deficit/hyperactivity disorder. Psychoneuroendocrinology 38:12–23CrossRefGoogle Scholar
  93. 93.
    Martino M, Rocchi G, Escelsior A, Fornaro M (2012) Immunomodulation mechanism of antidepressants: interactions between serotonin/norepinephrine balance and Th1/Th2 balance. Curr Neuropharmacol 10:97–123CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Natural Products and Food Research & Analysis (NatuRA), Department of Pharmaceutical SciencesUniversity of AntwerpWilrijkBelgium
  2. 2.Paediatric NeurologyUniversity Hospital AntwerpEdegemBelgium
  3. 3.STATUA, University of AntwerpEdegemBelgium
  4. 4.Cell Biology and Immunology GroupWageningen UniversityWageningenThe Netherlands

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