Gastrointestinal Factors in Autistic Disorder: A Critical Review

  • Craig A. Erickson
  • Kimberly A. Stigler
  • Mark R. Corkins
  • David J. Posey
  • Joseph F. Fitzgerald
  • Christopher J. McDougle
Article

Abstract

Interest in the gastrointestinal (GI) factors of autistic disorder (autism) has developed from descriptions of symptoms such as constipation and diarrhea in autistic children and advanced towards more detailed studies of GI histopathology and treatment modalities. This review attempts to critically and comprehensively analyze the literature as it applies to all aspects of GI factors in autism, including discussion of symptoms, pathology, nutrition, and treatment. While much literature is available on this topic, a dearth of rigorous study was found to validate GI factors specific to children with autism.

Keywords

Autistic disorder; gastroenterology; pathophysiology 

References

  1. Afzal N., Murch S., Thirrupathy K., Berger L., Fagbemi A., Heuschkel R. (2003). Constipation with acquired megarectum in children with autism Pediatrics 112: 939–942PubMedCrossRefGoogle Scholar
  2. Ahearn W. H., Castine T., Nault K., Green G. (2001). An assessment of food acceptance in children with autism or pervasive developmental disorder-not otherwise specified Journal of Autism and Developmental Disorders 31: 505–511PubMedCrossRefGoogle Scholar
  3. Alberti A., Pirrone P., Elia M., Waring R. H., Romano C. (1999). Sulphation deficit in “low-functioning” autistic children: A pilot study Biological Psychiatry 46: 420–424PubMedCrossRefGoogle Scholar
  4. American Psychiatric Association, (1987). Diagnostic and statistical manual of mental disorders (3rd ed., revised). American Psychiatric AssociationGoogle Scholar
  5. Banov C. H. (1979). Risks with controlling diet Journal of Autism and Developmental Disorders 9: 135–136PubMedCrossRefGoogle Scholar
  6. Black C., Kaye J. A., Jick H. (2002). Relation of childhood gastrointestinal disorders to autism: Nested case–control study using data from the UK General Practice Research Database British Medical Journal 325: 419–421PubMedCrossRefGoogle Scholar
  7. Carey T., Ratliff-Schaub K., Funk J., Weinle C., Myers M., Jenks J. (2002). Double-blind placebo-controlled trial of secretin: Effects on aberrant behavior in children with autism Journal of Autism and Developmental Disorders 32: 161–167PubMedCrossRefGoogle Scholar
  8. Chez M. G., Buchanan C. P., Bagan B. T. (2000). Secretin and autism: A two part clinical investigation Journal of Autism and Developmental Disorders 30: 87–94PubMedCrossRefGoogle Scholar
  9. Cohen D. J., Johnson W. T., Caparulo B. K. (1976). Pica and elevated blood lead level in autistic and atypical children American Journal of Diseases of Children 130: 47–48PubMedGoogle Scholar
  10. Coniglio S. J., Lewis J. D., Lang C., Burns T. G. (2001). A randomized, double-blind, placebo controlled trial of single-dose intravenous secretin as a treatment for children with autism Journal of Pediatrics 138: 649–655PubMedCrossRefGoogle Scholar
  11. Corbett, B., Khan, K., Czapansky-Beilman, D., & Brady, N. (2001). A double-blind, placebo-controlled crossover study investigating the effect of porcine secretin in children with autism. Clinical Pediatrics, 325–331Google Scholar
  12. Cornish E. (2002). Gluten and casein free diets in autism: A study of the effects on food choice and nutrition Journal of Human Nutrition and Dietetics 15: 261–269PubMedCrossRefGoogle Scholar
  13. D’Eufemia P., Celli M., Finocchiaro R., Pacifico L., Viozzi L., Zaccagnini M., Cardi E., Giardini O. (1996). Abnormal intestinal permeability in children with autism Acta Paediatrica 85: 1076–1079PubMedCrossRefGoogle Scholar
  14. Dalrymple N. J., Ruble L. A. (1992). Toilet training and behaviors of people with autism: Parent views Journal of Autism and Developmental Disorders 22: 265–275PubMedCrossRefGoogle Scholar
  15. Dunn-Geier J., Ho H. H., Auersperg E., Coyle D. (2000). Effect of secretin on children with autism: A randomized controlled trial Developmental Medicine & Child Neurology 42: 796–802CrossRefGoogle Scholar
  16. Evangeliou A., Vlachonikolis I., Mihailidou H. (2003). Application of ketogenic diet in children with autistic behavior: Pilot study Journal of Child Neurology 18: 113–118PubMedCrossRefGoogle Scholar
  17. Field D., Garland M., Williams K. (2003). Correlates of specific childhood feeding problems Journal of Pediatric Child Health 39: 299–304CrossRefGoogle Scholar
  18. Finegold S. M., Molitoris D., Song Y., Liu C., Vaisanen M. L., Bolte E., McTeague M., Sandler R., Wexler H. (2002). Gastrointestinal microflora studies in late-onset autism Clinical Infectious Diseases 35: S6–S16PubMedCrossRefGoogle Scholar
  19. Fombonne E., Chakrabarti S. (2001). No evidence for a new variant of measles-mumps-rubella-induced autism Pediatrics 108(4): E58PubMedCrossRefGoogle Scholar
  20. Furlano R. L., Anthony A., Day R., Brown A., McGarvey L., Thomson M. A., Davies S. E., Berelowitz M., Frobes A., Wakefield A. J., Walker-Smith J. A., Murch S. H. (2001). Colonic CD8 and gamma delta T-cell infiltration with epithelial damage in children with autism Journal of Pediatrics 138: 366–372PubMedCrossRefGoogle Scholar
  21. Hendrickson B. A., Turner J. R. (2002). MMR vaccination, ileal lymphoid nodular hyperplasia, and pervasive developmental disorder Lancet 359: 2051–2052PubMedCrossRefGoogle Scholar
  22. Hoekstra J. H. (1998). Toddler diarrhoea: A more nutritional disorder than a disease Archives of Disease in Childhood 79: 2–5PubMedCrossRefGoogle Scholar
  23. Honomichl R. D., Goodlin-Jones B. L., Burnham M. M., Hansen R. L., Anders T. F. (2002). Secretin and sleep in children with autism Child Psychiatry and Human Development 33: 107–123PubMedCrossRefGoogle Scholar
  24. Horvath K., Medeiros L., Rabszlyn A. (2000a). High prevalence of gastrointestinal symptoms in autistic children with autistic spectrum disorder Journal of Pediatric Gastroenterology and Nutrition 31: S174Google Scholar
  25. Horvath K., Papadimitriou J. C., Rabsztyn A., Drachenberg C., Tildon J. T. (1999). Gastrointestinal abnormalities in children with autistic disorder Journal of Pediatrics 135: 559–563PubMedCrossRefGoogle Scholar
  26. Horvath K., Perman J. A. (2002a). Autism and gastrointestinal symptoms Current Gastroenterology Reports 4: 251–258CrossRefGoogle Scholar
  27. Horvath K., Perman J. A. (2002b). Autistic disorder and gastrointestinal disease Current Opinion in Pediatrics 14: 583–587CrossRefGoogle Scholar
  28. Horvath K., Stefanatos G., Sokolski K. N., Wachtel R., Nabors L., Tildon J. T. (1998). Improved social and language skills after secretin administration in patients with autistic spectrum disorders Journal of the American Association for Academic Minority Physicians 9: 9–15Google Scholar
  29. Horvath K., Zielke R. H., Collins R. M., Rabsztyn A., Medeiros L. A., Perman J. (2000b). Secretin improves intestinal permeability in autistic children Journal of Pediatric Gastroenterology and Nutrition 31: S31Google Scholar
  30. Jyonouchi H., Sun S., Itokazu N. (2002). Innate immunity associated with inflammatory responses and cytokine production against common dietary proteins in patients with autism spectrum disorder Neuropsychobiology 46: 76–84PubMedCrossRefGoogle Scholar
  31. Kaminska B., Czaja M., Kozielska E., Mazur E., Korzon M. (2002). Use of secretin in treatment of childhood autism Medical Science Monitor 8: RA22–26PubMedGoogle Scholar
  32. Kawashima H., Mori T., Kashiwagi Y., Takekuma K., Hoshika A., Wakefield A. J. (2000). Detection and sequencing of measles virus from peripheral mononuclear cells from patients with inflammatory bowel disease and autism Digestive Diseases and Sciences 45: 723–729PubMedCrossRefGoogle Scholar
  33. Kern J. K., Miller V. S., Evans P. A., Trivedi M. H. (2002). Efficacy of porcine secretin in children with autism and pervasive developmental disroder Journal of Autism and Developmental Disorders 32: 153–160PubMedCrossRefGoogle Scholar
  34. Knivsberg A., Reichelt K. L., Nodland N., Hoien T. (1995). Autistic syndrome and diet: A follow-up study Scandinavian Journal of Education and Research 39: 223–236CrossRefGoogle Scholar
  35. Knivsberg A. M., Reichelt K. L., Hoien T., Nodland M. (2002). A randomized, controlled study of dietary intervention in autistic syndromes Nutritional Neuroscience 5: 251–261PubMedCrossRefGoogle Scholar
  36. Kokkonen J., Karttunen T. J. (2002). Lymphonodular hyperplasia on the mucosa of the lower gastrointestinal tract in children: An indication of enhanced immune response? Journal of Pediatric Gastroenterology and Nutrition 34: 42–46PubMedCrossRefGoogle Scholar
  37. Kuddo T., Nelson K. B. (2003). How common are gastrointestinal disorders in children with autism? Current Opinion in Pediatrics 15: 339–343PubMedCrossRefGoogle Scholar
  38. Lightdale J. R., Hayer C., Duer A., Lind-White C., Jenkins S., Siegel B., Elliot G. R., Heyman M. B. (2001). Effects of intravenous secretin on language and behavior of children with autism and gastrointestinal symptoms: A single-blinded, open-label pilot study Pediatrics 108: E90PubMedCrossRefGoogle Scholar
  39. Lightdale J. R., Siegel B., Heyman M. B. (2001). Gastrointestinal symptoms in autistic children Clinical Perspectives on Gastroenterology 1: 56–58Google Scholar
  40. Linday L. A. (1997). Oral famotidine: A potential treatment for children with autism Medical Hypotheses 48: 381–386PubMedCrossRefGoogle Scholar
  41. Linday L. A., Tsiouris J. A., Cohen I. L., Shindledecker R., DeCresce R. (2001). Famotidine treatment of children with autistic spectrum disorders: Pilot research using single subject research design Journal of Neural Transmission 108: 593–611PubMedCrossRefGoogle Scholar
  42. Loening-Baucke V. (1998). Constipation in children The New England Journal of Medicine 339: 1155–1156PubMedCrossRefGoogle Scholar
  43. Lucarelli S., Frediani T., Zingoni A. M., Ferruzzi F., Giardini O., Quintieri F., Barbato M., D’Eufemia P., Cardi E. (1995). Food allergy and infantile autism Panminerva Medica 37: 137–141PubMedGoogle Scholar
  44. Malloy C. A., Manning-Courtney P., Swayne S., Bean J., Brown J. M., Murray D. S., Kinsman A. M., Brasington M., Ulrich C. D. (2002). Lack of benefit of intravenous synthetic human secretin in the treatment of autism Journal of Autism and Developmental Disorders 32: 545–551CrossRefGoogle Scholar
  45. McCarthy D. M., Coleman M. (1979). Response of intestinal mucosa to gluten challenge in autistic subjects Lancet 2: 877–878PubMedCrossRefGoogle Scholar
  46. McMillin D. L., Richards D. G., Mein E. A., Nelson C. D. (1999). The abdominal brain and the enteric nervous system Journal of Alternative and Complementary Medicine 5: 575–586CrossRefGoogle Scholar
  47. Melmed R. D., Schneider C. K., Fabes R. A., Phillips J., Reichelt K. (2000). Metabolic markers and gastrointestinal symptoms in children with autism and related disorders Journal of Pediatric Gastroenterology and Nutrition 3: S31–S32Google Scholar
  48. Murch S. H., MacDonald T. T., Walker-Smith J. A., Levin M., Lionetti P., Klein N. J. (1993). Disruption of sulphated glycosaminoglycans in intestinal inflammation Lancet 341: 711–714PubMedCrossRefGoogle Scholar
  49. O’Banion D., Armstrong B., Cummings R. A., Strange J. (1978). Disruptive behavior: A dietary approach Journal of Autism and Childhood Schizophrenia 8: 325–337PubMedCrossRefGoogle Scholar
  50. Owley T., McMahon W., Cook E. H., Laulhere T., South M., Zellmer L. (2001). Multisite, double blind, placebo-controlled trial of porcine secretin in autism Journal of the American Academy of Child and Adolescent Psychiatry 40: 1293–1299PubMedCrossRefGoogle Scholar
  51. Patel N. C., Yeh J. Y., Shepherd M. D., Crismon M. L. (2002). Secretin treatment for autistic disorder: A critical analysis Pharmacotherapy 22: 905–914PubMedCrossRefGoogle Scholar
  52. Pavone L., Fiumara A., Bottaro G., Mazzone D., Coleman M. (1997). Autism and celiac disease: Failure to validate the hypothesis that a link might exist Biological Psychiatry 42: 72–75PubMedCrossRefGoogle Scholar
  53. Quigley E. M. (2000). Autism and the gastrointestinal tract American Journal of Gastroenterology 95: 2154–2156PubMedCrossRefGoogle Scholar
  54. Raiten D. J., Massaro T. (1986). Perspectives on the nutritional ecology of autistic children Journal of Autism and Developmental Disorders 16: 133–143PubMedCrossRefGoogle Scholar
  55. Reichelt K. L., Ekrein J., Scott H. (1990). Gluten, milk proteins and autism: Dietary intervention effects on behavior and peptide secretion Journal of Applied Nutrition 42: 1–11Google Scholar
  56. Reichelt K. L., Knivsberg A. M., Lind G., Nodland M. (1991). Probable etiology and possible treatment of childhood autism Brain Dysfunction 4: 308–319Google Scholar
  57. Roberts W., Weaver L., Brian J., Bryson S. (2001). Repeated doses of porcine secretin in the treatment of autism: A randomized, placebo controlled trial Pediatrics 107: e71PubMedCrossRefGoogle Scholar
  58. Sandler A. D., Sutton K. A., DeWeese J., Girardi M. A., Sheppard V., Bodfish J. W. (1999). Lack of benefit of a single dose of synthetic human secretin in the treatment of autism and pervasive developmental disorder The New England Journal of Medicine 341: 1801–1806PubMedCrossRefGoogle Scholar
  59. Sandler R. H., Finegold S. M., Bolte E. R., Buchanan C., Maxwell A. P., Vaisanen M. L., Nelson M. N., Wexler H. (2000). Short-term benefit from oral vancomycin treatment of regressive-onset autism Journal of Child Neurology 15: 429–435PubMedCrossRefGoogle Scholar
  60. Shearer T. R., Larson K., Neushwander J., Gedney B. (1982). Minerals in the hair and nutrient intake of autistic children Journal of Autism and Developmental Disorders 12: 25–34PubMedCrossRefGoogle Scholar
  61. Sponheim E., Oftedal G., Helverschou B. (2002). Multiple doses of secretin in the treatment of autism: A controlled study Acta Paediatrica 91: 540–545PubMedCrossRefGoogle Scholar
  62. Tanguay P. E. (2002). Commentary: The primacy of the scientific method Journal of the American Academy of Child and Adolescent Psychiatry 41: 1322–1323PubMedCrossRefGoogle Scholar
  63. Taylor B., Miller E., Lingam R. (2002). Measles, mumps, and rubella vaccination and bowel problems or developmental regression in children with autism: Population study British Medical Journal 324: 393–396PubMedCrossRefGoogle Scholar
  64. Torrente F., Ashwood P., Day R., Machado N., Furlano R. I., Anthony A., Davies S. E., Wakefield A. J., Thomson M. A., Walker-Smith J. A., Murch S. H. (2002). Small intestinal enteropathy with epithelial IgG and complement deposition in children with regressive autism Molecular Psychiatry 7: 375–382PubMedCrossRefGoogle Scholar
  65. Uhlmann V., Martin C. M., Scheils O., Pilkington L., Silva I., Killalea A., Murch S. B., Walker-Smith J. A., Thomson M. A., Wakefield A. J., O’Leary J. J. (2002). Potential viral pathogenic mechanism for a new variant inflammatory bowel disease Journal of Clinical Pathology – Molecular Pathology 55: 84–90Google Scholar
  66. Unis I. S., Munson J. A., Rogers S. J., Goldson E., Osterling J., Gabriels R., Abbott R. D., Dawson G. (2002). A randomized, double-blind, placebo controlled trial of porcine versus synthetic secretin for reducing symptoms of autism Journal of the American Academy of Child and Adolescent Psychiatry 41: 1315–1321PubMedCrossRefGoogle Scholar
  67. Wakefield A. J., Anthony A., Murch S. H., Thomson M. A., Montgomery S. M., Davies S., O’Leary J. J., Berelowitz M., Walker-Smith J. A. (2003). Enterocolitis in children with developmental disabilities The American Journal of Gastroenterology 95: 2285–2295CrossRefGoogle Scholar
  68. Wakefield A. J., Anthony A., Schepelmann S., Kawashima H., Sim R., Khan K., Murch S. H., Dhillon A. P., Montgomery S. M., Thomson M. A., Thomas J., Walker-Smith J. A. (1998a). Persistent measles virus (MV) infection and immunodeficiency in children with autism, ileo-colonic lymphonodular hyperplasia and non-specific colitis Gut 42: A86Google Scholar
  69. Wakefield A. J., Murch S. H., Anthony A., Linnell J., Casson D. M., Malik M., Berelowitz M., Dhillon A. P., Thomson M. A., Harvey P., Valentine A., Davies S. E. (1998b). Ileal-lymphoid-nodular hyperplasia, non-specific colitis, and pervasive developmental disorder in children Lancet 351: 637–641CrossRefGoogle Scholar
  70. Wakefield A. J., Murch S. H., Anthony A., Linnell J., Thomas J., Berelowitz M., Dhillon A. P., Thomson M. A., Davies S. E., Walker-Smith J. A. (1998c). Autistic enteropathy: A new inflammatory bowel disease? Gut 42: A84–A85Google Scholar
  71. Wakefield A. J., Puleston J. M., Montgomery S. M., Anthony A., O’Leary J. J., Murch S. H. (2002). Review article: The concept of entero-colonic encephalopathy, autism and opioid receptor ligands Alimentary Pharmacology and Therapeutics 16: 663–674PubMedCrossRefGoogle Scholar
  72. Walker-Smith J. A., Andrews J. (1972). Alpha-antitrypsin, autism and celiac disease Lancet 2: 883–884PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, Inc. 2005

Authors and Affiliations

  • Craig A. Erickson
    • 1
    • 2
    • 3
  • Kimberly A. Stigler
    • 1
    • 3
  • Mark R. Corkins
    • 2
    • 3
  • David J. Posey
    • 1
    • 3
  • Joseph F. Fitzgerald
    • 2
    • 3
  • Christopher J. McDougle
    • 1
    • 2
    • 3
    • 4
  1. 1.Department of PsychiatryIndiana University School of MedicineIndianapolisUSA
  2. 2.Department of PediatricsIndiana University School of MedicineIndianapolisUSA
  3. 3.James Whitcomb Riley Hospital for ChildrenIndianapolisUSA
  4. 4.Department of PsychiatryIndiana University School of MedicineIndianapolisUSA

Personalised recommendations