ADHD, a Food-Induced Hypersensitivity Syndrome: in Quest of a Cause The effects of a restricted elimination diet (RED) on ADHD, ODD and comorbid somatic complaints, and a preliminary survey of the mechanisms of an RED
Een wetenschappelijke proeve op het gebied van de Medische Wetenschappen
Proefschrift
ter verkrijging van de graad van doctor aan de Radboud Universiteit Nijmegen op gezag van de rector magnificus prof. mr. S.C.J.J. Kortmann volgens besluit van het college van decanen in het openbaar te verdedigen op maandag 10 oktober 2011 om 15.30 uur precies
door
Liduina Maria Josephina Pelsser geboren op 8 januari 1956 te Epen (Wittem)
Contents Preface: how it all began........................................................................................................ 9 A poem to start with: ‘Fidgety Philip’.................................................................................. 11 Chapter 1. General introduction.......................................................................................... 15 1.1. ADHD........................................................................................................................ 17 1.2. ADHD-NOS.............................................................................................................. 22 1.3. Comorbid disorders................................................................................................. 22 1.4. The impact of ADHD................................................................................................ 23 1.5. Aetiology: genetic and environmental factors involved.......................................... 24 1.6. Food as a specific environmental risk factor of ADHD.......................................... 27 1.7. Additive and supplement studies............................................................................ 28 1.8. RED studies.............................................................................................................. 29 1.9. Current assessment and therapy of ADHD............................................................ 31 1.10. The role of food in the current therapy of ADHD.................................................... 32 1.11. Aim and structure of this thesis............................................................................... 33 References................................................................................................................ 36
Part 1: t he effect of a restricted elimination diet (RED) on ADHD, ODD and comorbid physical and sleep complaints (chapters 2, 3 and 4) Chapter 2. Effects of an RED on ADHD and ODD, an exploratory study.................... 47 avourable effects of an elimination diet on the behaviour of children with ADHD: a pilot Study. F Pelsser LM, Buitelaar JK. Ned Tijdschr Geneeskd 2002;146:2543-47 (in Dutch).
Chapter 3. Effects of an RED on ADHD and ODD, an open RCT................................. 59 A randomised controlled trial into the effects of food on ADHD. Pelsser LM, Frankena K, Toorman J, Savelkoul HF, Pereira RR, Buitelaar JK. Eur Child Adolesc Psychiatry 2009;18:12-19.
Chapter 4. Effects of an RED on physical complaints, an open RCT.......................... 77 Effects of food on physical and sleep complaints in children with ADHD: a randomised controlled pilot study. Pelsser LM, Frankena K, Buitelaar JK, Rommelse NN. Eur J Pediatr 2010;169:1129-38.
Part 2: Mechanisms of an RED in ADHD (chapters 5, 6 and 7) Chapter 5. Is ADHD a hypersensitivity disorder?........................................................... 99 ADHD as a (non) allergic hypersensitivity disorder: a hypothesis. Pelsser LM, Buitelaar JK, Savelkoul HF. Pediatr Allergy Immunol 2009;20:107-12.
Chapter 6. Effects of an RED on ADHD, an open RCT with blinded measurements and blood tests....................................................................113 Effects of a restricted elimination diet on the behaviour of children with attention-deficit hyperactivity disorder (INCA study): a randomised controlled trial. Pelsser LM, Frankena K, Toorman J, Savelkoul HF, Haagen T, Dubois AF, Pereira RR, Rommelse NN, Buitelaar JK. Lancet 2011;377:494-503.
Chapter 7. Effects of an RED on family structure......................................................... 143 Are the effects of a restricted elimination diet on ADHD and ODD mediated by changes in family structure: a further analysis of the INCA study. Pelsser LM, van Steijn DJ, Frankena K, Toorman J, Buitelaar JK, Rommelse NN. Submitted.
Chapter 8. Summary......................................................................................................... 161
8.1. General introduction............................................................................................... 163 8.2. Part 1...................................................................................................................... 163 8.3. Part 2...................................................................................................................... 166 8.4. General discussion................................................................................................ 167 8.5. Conclusions and recommendations..................................................................... 167 8.6. Acknowledgement and consensus....................................................................... 170
Chapter 9. General discussion........................................................................................ 173 9.1. The Impact of an RED on ADHD........................................................................... 175 9.2. The Impact of an RED on ODD............................................................................. 182 9.3. The impact of an RED on physical complaints and sleep problems in children with ADHD............................................................................................ 184 9.4. The implications of the RED findings for our knowledge of ADHD aetiology...................................................................................................... 185 9.5. The mechanism underlying the effects of an RED.............................................. 192 9.6. Follow-up research................................................................................................. 194 9.7. Practical implications and implementation of an RED in general practice: a proposal for a multimodal algorithm for diagnosis and treatment................... 203 9.8. Suggestions for DSM-V.......................................................................................... 210 9.9. To conclude............................................................................................................ 212 References.............................................................................................................. 214
Appendix: INCA research protocol .................................................................................. 223 Parents’ and children’s accounts: RED research in real life......................................... 277 Samenvatting (summary in Dutch).................................................................................... 292 A poem to end with: ‘Perky Peter’ (restrict your diet and be quiet).............................299 Postface: how it all turned out........................................................................................... 303 Dankwoord (acknowledgements in Dutch)...................................................................... 307 Abbreviations....................................................................................................................... 311