Autism Research Institute

Research Documenting Biomedical Problems in Autism - February 2009

The following index links to citations describing emerging findings in autism research:

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Autism and the Gastrointestinal System

Afzal N, et al. Constipation with acquired megarectum in children with autism. Pediatrics. 2003 Oct;112(4):939-42.

Arvilommi H, Isolauri E.Kalliomäki M, Poussa T, Salminen S. Probiotics and prevention of atopic disease: 4-year follow-up of a randomised placebo-controlled trial. Lancet. 2003 361(9372):1869-71.

Ashwood P et al.  Intestinal lymphocyte populations in children with regressive autism: evidence for extensive mucosal immunopathology. J Clin Immunol. 2003 Nov;23(6):504-17. 

Ashwood P, Wakefield AJ. Immune activation of peripheral blood and mucosal CD3+ lymphocyte cytokine profiles in children with autism and gastrointestinal symptoms. J Neuroimmunol. 2006 Apr;173(1-2):126-34.

Balzola F, Barbon V, Repici A, Rizzetto M. Panenteric IBD-like disease in a patient with regressive autism shown for the first time by the wireless capsule enteroscopy: another piece in the jigsaw of this gut-brain syndrome? Am J Gastro. 2005; 979-981.

Balzola F, et al. Autistic enterocolitis: confirmation of a new inflammatory bowel disease in an Italian cohort of patients. Gastroenterology. 2005;128:Suppl.2;A-303.

Balzola F, et al. Autistic Enterocolitis in childhood: the early evidence of the later Crohn’s disease in autistic adulthood? Gastroenterology April 2007 Vol 132, N. 4, suppl 2 W 1100 A 660

Balzola F, et al.  Beneficial behavioural effects of IBD therapy and gluten/casein-free diet in an Italian cohort of patients with autistic enterocolitis followed over one year. Gastroenterology, April 2006 Vol 130 Number 4 suppl. 2 S1364 A-21.

Biller JA, Katz AJ, Flores AF, Buie TM, Gorbach SL. Treatment of recurrent Clostridium difficile colitis with Lactobacillus GG. J Pediatr Gastroenterol Nutr. 1995 Aug;21(2):224-6.

Billoo AG, Memon MA, Khaskheli SA, et al.  Role of probiotic Saccharomyces boulardii in management and prevention of diarrhea.  World J Gastroenterol. 2006;12:4557-4560.

Black C, Kaye JA, Jick H. Relation of childhood gastrointestinal disorders to autism: nested case-control study using data from the UK General Practice Research Database. BMJ. 2002 Aug 24;325(7361):419-21.

Binstock T. Intra-monocyte pathogens delineate autism subgroups. Med Hypotheses. 2001 Apr;56(4):523-31. 

Binstock T. Anterior insular cortex: linking intestinal pathology and brain function in autism-spectrum subgroups. Med Hypotheses 2001 57(6):714-7.

Borruel N, et al. Increased mucosal tumour necrosis factor alpha production in Crohn's disease can be downregulated ex vivo by probiotic bacteria. Gut. 2002 Nov;51(5):659-64.

Bousvaros A,et al; and the Members of the Challenges in Pediatric IBD Study Groups. Challenges in pediatric inflammatory bowel disease. Inflamm Bowel Dis. 2006 Sep;12(9):885-913.

Buchman AL, et al. Hyperbaric oxygen therapy for severe ulcerative colitis. J Clin Gastroenterol. 2001Oct;33(4):337-9.

Buts JP, De Keyser N. Effects of Saccharomyces boulardii on intestinal mucosa. Dig Dis Sci. 2006 Aug;51(8):1485-92.

Cade R, et al. Autism and schizophrenia: intestinal disorders. Nutritional Neuroscience 3: 57-72, 2000. 

Cade JR, et al. Autism and schizophrenia linked to malfunctioning enzyme for milk protein digestion. Autism, Mar 1999. 

Czerucka D, et al. Experimental effects of Saccharomyces boulardii on diarrheal pathogens. Microbes Infect, 2002. 4(7): p. 733-9.

DeFelice ML, et al. Intestinal cytokines in children with pervasive developmental disorders. Am J Gastroenterol 98(8): 1777-82: 2003.

del Giudice MM, Brunese FP. Probiotics, prebiotics, and allergy in children: what's new in the last year? J Clin Gastroenterol. 2008 Sep;42 Suppl 3 Pt 2:S205-8.

D'Eufemia P, et al. Abnormal intestinal permeability in children with autism. Acta Paediatr. 1996 Sep;85(9):1076-9.

Fedorak RN, Madsen KL. Probiotics and the management of inflammatory bowel disease. Inflamm Bowel Dis. 2004 May;10(3):286.

Forsberg G, et al. Presence of bacteria and innate immunity of intestinal epithelium in childhood celiac disease. Am J Gastroenterol.  2004 May;99(5):894-904. 

Furlano RI, et al. Colonic CD8 and gamma delta T-cell infiltration with epithelial damage in children with autism. J Pediatr. 2001 Mar;138(3):366-72.

Ghosh S, et al. Probiotics in inflammatory bowel disease: is it all gut flora modulation? Gut. 2004 May;53(5):620-2.

Gonzalez L, Lopez K, Navarro D, Negron L, Flores L, Rodriguez R, Martinez M, Sabra A. Endoscopic and Histological Characteristics of the digestive mucosa in autistic children with gastrointestinal symptoms. Arch Venez Pueric Pediatr 69;1:19-25

Gottschall, Elaine G. Breaking the Vicious Cycle: Intestinal Health Through Diet. Ontario: Kirkton Press. 1994.

Hadjivassiliou M et al.  Does cryptic gluten sensitivity play a part in neurological illness?  Lancet. 1996 Feb 10;347(8998):369-71.

Hart AL, et al. Modulation of human dendritic cell phenotype and function by probiotic bacteria. Gut. 2004 Nov;53(11):1602-9.

Haskey N, Dahl WJ. Synbiotic therapy: a promising new adjunctive therapy for ulcerative colitis. Nutr Rev. 2006 Mar;64(3):132-8.

Hassall E. Decisions in diagnosing and managing chronic gastroesophageal reflux disease in children. J Pediatr. 2005 Mar;146(3 Suppl):S3-12.

Homan M, Baldassano RN, Mamula P. Managing complicated Crohn's disease in children and adolescents. Nat Clin Pract Gastroenterol Hepatol. 2005 Dec;2(12):572-9.

Horvath K et al.  Gastrointestinal abnormalities in children with autistic disorder. J Pediatr. 1999 Nov;135(5):559-63.

Horvath K, Perman JA. Autism and gastrointestinal symptoms. Curr Gastroenterol Rep. 2002 Jun;4(3):251-8.

Horvath K, Perman JA. Autistic disorder and gastrointestinal disease. Curr Opin Pediatr. 2002 Oct;14(5):583-7.

Iacono G et al.  Intolerance of cow's milk and chronic constipation in children.  N Engl J Med. 1998 Oct 15;339(16):1100-4. 

Işeri SO, Sener G, Sağlam B, Gedik N, Ercan F, Yeğen BC. Oxytocin ameliorates oxidative colonic inflammation by a neutrophil-dependent mechanism. Peptides. 2005 Mar;26(3):483-91.

Kawashima H et al. Detection and sequencing of measles virus from peripheral mononuclear cells from patients with inflammatory bowel disease and autism. Dig Dis Sci. 2000 Apr;45(4):723-9. 

Koch TR, et al. Induction of enlarged intestinal lymphoid aggregates during acute glutathione depletion in a murine model. Dig Dis Sci 2000. 45(11): 2115-21.

Kruis W. Antibiotics and probiotics in inflammatory bowel disease. Aliment Pharmacol Ther.  2004 Oct;20 Suppl 4:75-8. 

Kuddo T, Nelson KB. How common are gastrointestinal disorders in children with autism. Curr Opin Pediatr 2003: 15(3); 339-343.

Kushak R, Winter H, Farber N, Buie T. Gastrointestinal symptoms and intestinal disaccharidase activities in children with autism. Abstract of presentation to the North American Society of Pediatric Gastroenterology, Hepatology, and Nutrition, Annual Meeting, October 20-22, 2005, Salt Lake City, Utah.

Levy S, et al. Children with autistic spectrum disorders. I: Comparison of placebo and single dose of human synthetic secretin. Arch. Dis. Child. 2003;88;731-736.

Lewis JD, et al. An open-label trial of the PPAR-gamma ligand rosiglitazone for active ulcerative colitis. Am J Gastroenterol. 2001 Dec;96(12):3323-8.

Liu Z, Li N, Neu J. Tight junctions, leaky intestines, and pediatric diseases. Acta Paediatr. 2005 Apr;94(4):386-93.

Macdonald A. Omega-3 fatty acids as adjunctive therapy in Crohn’s disease. Gastroenterol Nurs. 2006 Jul-Aug;29(4):295-301.

Melmed RD, Schneider CK, Fabes RA. Metabolic markers and gastrointestinal symptoms in children with autism and related disorders. J Pediatr Gastroenterol Nutr 2000:31(suppl 2)S31-32.

Ménard S, Candalh C, Bambou JC, Terpend K, Cerf-Bensussan N, Heyman M. Lactic acid bacteria secrete metabolites retaining anti-inflammatory properties after intestinal transport. Gut. 2004 Jun;53(6):821-8.

Parracho HM, Bingham MO, Gibson GR, McCartney AL. Differences between the gut microflora of children with autistic spectrum disorders and that of healthy children. J Med Microbiol. 2005 Oct;54(Pt 10):987-91.

Qin HL, Shen TY, Gao ZG, Fan XB, Hang XM, Jiang YQ, Zhang HZ. Effect of lactobacillus on the gut microflora and barrier function of rats with abdominal infection. World J Gastroenterol. 2005 May 7;11(17):2591-6.

Quigley EM, Hurley D. Autism and the gastrointestinal tract. Am J Gastroenterol. 2000 Sep;95(9):2154-6. Reichelt KL, Knivsberg AM. Can the pathophysiology of autism be explained by the nature of the discovered urine peptides? Nutr Neurosci.  2003 Feb;6(1):19-28. 

Reichelt KL, et al. Probable Etiology and Possible Treatment of Childhood Autism. Brain Dysfuntion 1991; 4: 308-319.

Rimland, B. Secretin treatment for autism. N Engl J Med 2000. 342(16): 1216-7; author reply 1218.

Romano C, et al. Usefulness of omega-3 fatty acid supplementation in addition to mesalazine in maintaining remission in pediatric Crohn's disease: a double-blind, randomized, placebo-controlled study. World J Gastroenterol. 2005 Dec 7;11(45):7118-21.

Salminen S, Isolauri E, Salminen E. Clinical uses of probiotics for stabilizing the gut mucosal barrier: successful strains and future challenges. Antonie Van Leeuwenhoek. 1996 Oct;70(2-4):347-58.

Sandler RH, et al. Short-term benefit from oral vancomycin treatment of regressive-onset autism. J Child Neurol. 2000 Jul;15(7):429.

Schneider CK, Melmed RD, Barstow LE, Enriquez FJ, Ranger-Moore J, Ostrem JA. Oral Human Immunoglobulin for Children with Autism and Gastrointestinal Dysfunction: A Prospective, Open-Label Study. J Autism Dev Disord. 2006 Jul 15.

Sido B, Hack V, Hochlehnert A, Lipps H, Herfarth C, Droge W. Impairment of intestinal glutathione synthesis in patients with inflammatory bowel disease. Gut. 1998 Apr;42(4):485-92.

Sienkiewicz-Szapka E, et al. Transport of bovine milk derived opioid peptides across a Caco-2 monolayer, Int Dairy J. 2008.

Song Y, Liu C, Finegold SM. Real-time PCR quantitation of clostridia in feces of autistic children. Appl Environ Microbiol. 2004 Nov;70(11):6459-65.

Sougioultzis S, et al. Saccharomyces boulardii produces a soluble anti-inflammatory factor that inhibits NF-kappaB-mediated IL-8 gene expression. Biochem Biophys Res Commun. 2006 Apr 28;343(1):69-76.

Sturniolo, G.C., et al. Zinc supplementation tightens "leaky gut" in Crohn's disease. Inflamm Bowel Dis, 2001. 7(2): p. 94-8.

Surawicz CM. Probiotics, antibiotic-associated diarrhoea and Clostridium difficile diarrhoea in humans. Best Pract Res Clin Gastroenterol. 2003 Oct;17(5):775-83.

Taylor B, Miller E, Lingam R, Andrews N, Simmons A, Stowe J. Measles, mumps, and rubella vaccination and bowel problems or developmental regression in children with autism: population study. BMJ. 2002 Feb 16;324(7334):393-6.

Torrente F, Anthony A. Focal-enhanced gastritis in regressive autism with features distinct from Crohn’s disease and helicobacter Pylori gastritis. Am J Gastroenterol 2004 Apr;99(4):598-605.

Torrente F et al.  Small intestinal enteropathy with epithelial IgG and complement deposition in children with regressive autism. Mol Psychiatry. 2002;7(4):375-82, 334. 

Uhlmann V et al.  Potential viral pathogenic mechanism for new variant inflammatory bowel disease. Mol Pathol. 2002 Apr;55(2):84-90.

Valicenti-McDermott M, et al. Frequency of gastrointestinal symptoms in children with autistic spectrum disorders and association with family history of autoimmune disease. J Dev Behav Pediatr. 2006 Apr;27(2 Suppl):S128-36.

Valicenti-McDermott MD, McVicar K, Cohen HJ, Wershil BK, Shinnar S. Gastrointestinal symptoms in children with an autism spectrum disorder and language regression. Pediatr Neurol. 2008 Dec;39(6):392-8.

Wakefield AJ, Ashwood P, Limb K, Anthony A. The significance of ileo-colonic lymphoid nodular hyperplasia in children with autistic spectrum disorder. Eur J Gastroenterol Hepatol. 2005 Aug;17(8):827-36.

Wakefield AJ et al. Ileal-lymphoid-nodular hyperplasia, non-specific colitis, and pervasive developmental disorder in children. Lancet. 1998 28;351(9103):637-41.

Wakefield AJ. Enterocolitis, autism and measles virus. Mol Psychiatry. 2002;7 Suppl 2:S44-6.

Wakefield AJ. The gut-brain axis in childhood developmental disorders. J Pediatr Gastroenterol Nutr. 2002 May-Jun;34 Suppl 1:S14-7.

Wakefield AJ et al. Review article: the concept of entero-colonic encephalopathy, autism and opioid receptor ligands. Aliment Pharmacol Ther 2002 16(4):663-74.

Wakefield AJ et al. Enterocolitis in children with developmental disorders. Am J Gastroenterol. 2000 Sep;95(9):2285-95.

Wakefield AJ, et al. Autism, viral infection and measles-mumps-rubella vaccination. Isr Med Assoc J. 1999 Nov;1(3):183-7.

Wakefield AJ.  MMR vaccination and autism. Lancet. 1999 Sep 11;354(9182):949-50.

Welch MG, Welch-Horan TB, Anwar M, Anwar N, Ludwig RJ, Ruggiero DA. Brain effects of chronic IBD in areas abnormal in autism and treatment by single neuropeptides secretin and oxytocin. J Mol Neurosci 2005; 25(3):259-74.

White JF. Intestinal pathophysiology in autism. Exp Biol Med (Maywood). 2003 Jun;228(6):639-49.

Whiteley P, Shattock P. Biochemical aspects in autism spectrum disorders: updating the opioid-excess theory and presenting new opportunities for biomedical intervention. Expert Opin Ther Targets. 2002 Apr;6(2):175-83.  

Autism and Biomedical Treatment back to top

Goin-Kochel RP, Mackintosh VH, Myers, BJ. Parental reports on the efficacy of treatments and therapies of their children with autism spectrum disorders. Res Autism Spectr Disord. 2009, doi:10.1016/j.rasd.2008.11.001.

O'Hara NH, Szakacs GM. The recovery of a child with autism spectrum disorder through biomedical interventions. Altern Ther Health Med. 2008 Nov-Dec;14(6):42-4.

Nutritional Deficiencies, Supplements, & Diet back to top

Adams JB, Holloway C. Pilot study of a moderate dose multivitamin/mineral supplement for children with autistic spectrum disorder. J Altern Complement Med. 2004 Dec;10(6):1033-9.

Adams JB, George F, Audhya T. Abnormally high plasma levels of vitamin B6 in children with autism not taking supplements compared to controls not taking supplements. J Altern Complement Med. 2006 Jan-Feb;12(1):59-63.

Aldred S, et al. Plasma amino acid levels in children with autism and their families. J Autism Dev Disord. 2003 Feb;33(1):93-7.

Amminger GP, Berger GE, Schafer MR, Klier C, Friedrich MH, Feucht M. Omega-3 Fatty Acids Supplementation in Children with Autism: A Double-blind Randomized, Placebo-controlled Pilot Study. Biol Psychiatry. 2006 Aug 22.

Andersen IM, et al. Melatonin for Insomnia in Children With Autism Spectrum Disorders. J Child Neurol. 2008 Jan 8.

Arnold GL et al. Plasma amino acids profiles in children with autism: potential risk of nutritional deficiencies. J Autism Dev Disord 2003 33(4):449-54.

Ashkenazi A, Levin S, Krasilowsky D. Gluten and autism. Lancet. 1980 Jan 19;1(8160):157.

Baker SB, Worthley LI. The essentials of calcium, magnesium and phosphate metabolism: part I. Physiology. Crit Care Resusc. 2002 Dec;4(4):301-6.

Barthelemy C, et al. Biological and clinical effects of oral magnesium and associated magnesium-vitamin B6 administration on certain disorders observed in infantile autism. Therapie. 1980 Sep-Oct;35(5):627-32.

Bolman WM, Richmond JA. A double-blind, placebo-controlled, crossover pilot trial of low dose dimethylglycine in patients with autistic disorder. J Autism Dev Disord. 1999 Jun;29(3):191-4.

Bruni O, et al. L -5-Hydroxytryptophan treatment of sleep terrors in children. Eur J Pediatr. 2004 Jul;163(7):402-7.

Bubenik GA, et al. Propsects of the clinical utilization of melatonin. Biological Signals and Receptors. 1998;7:195-219.

Bu B, Ashwood P, Harvey D, King IB, Water JV, Jin LW. Fatty acid compositions of red blood cell phospholipids in children with autism. Prostaglandins Leukot Essent Fatty Acids. 2006 Apr;74(4):215-21.

Carlton R et al. Rational dosages of nutrients have a prolonged effect on learning disabilities. Alternative Therapies 2000; 6:85-91.

Christison GW, Ivany K. Elimination diets in autism spectrum disorders: any wheat amidst the chaff? J Dev Behav Pediatr. 2006 Apr;27(2 Suppl):S162-71.

Connors SL, Crowell DE. Secretin and autism: the role of cysteine. J Am Acad Child Adolesc Psychiatry. 1999 Jul;38(7):795-6.

Curtis LT, Patel K. Nutritional and environmental approaches to preventing and treating autism and attention deficit hyperactivity disorder (ADHD): a review. J Altern Complement Med. 2008 Jan-Feb;14(1):79-85.

Dolske MC, Spollen J, McKay S, Lancashire E, Tolbert L. A preliminary trial of ascorbic acid as supplemental therapy for autism. Prog Neuropsychopharmacol Biol Psychiatry. 1993 Sep;17(5):765-74.

Elder JH. The gluten-free, casein-free diet in autism: an overview with clinical implications.  Nutr Clin Pract. 2008 Dec-2009 Jan;23(6):583-8.

El Idrissi A et al.  Prevention of epileptic seizures by taurine. Adv Exp Med Biol. 2003;526:515-25.

Erdeve O et al.  The probiotic effect of Saccharomyces boulardii in a pediatric age group. J Trop Pediatr.  2004 Aug;50(4):234-6. 

Fernstrom JD. Can nutrient supplements modify brain function? Am J Clin Nutr. 2000 Jun;71(6 Suppl):1669S-75S.

Finegold SM et al. Gastrointestinal microflora studies in late-onset autism. Clin Infect Dis  2002 35 (Suppl 1):S6-S16.

Giannotti F, Cortesi F, Cerquiglini A, Bernabei P. An open-label study of controlled-release melatonin in treatment of sleep disorders in children with autism. J Autism Dev Disord. 2006 Aug;36(6):741-52.

Gill HS, Rutherfurd KJ, Prasad J, Gopal PK. Enhancement of natural and acquired immunity by Lactobacillus rhamnosus (HN001), Lactobacillus acidophilus (HN017) and Bifidobacterium lactis (HN019). Br J Nutr. 2000 Feb;83(2):167-76.

Grattan-Smith PJ, Wilcken B, Procopis PG, Wise GA. The neurological syndrome of infantile cobalamin deficiency: developmental regression and involuntary movements. Mov Disord. 1997 Jan;12(1):39-46.

Herbert V. Detection of malabsorption of vitamin B12 due to gastric or intestinal dysfunction. Semin Nucl Med.  1972 Jul;2(3):220.

Ishizaki A, Sugama M, Takeuchi N. Usefulness of melatonin for developmental sleep and emotional/behavior disorders—studies of melatonin trial on 50 patients with developmental disorders. No To Hattatsu. 1999 Sep;31(5):428-37.

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Kern JK, Miller VS, Cauller PL, Kendall PR, Mehta PJ, Dodd M. Effectiveness of N,N-dimethylglycine in autism and pervasive developmental disorder. J Child Neurol. 2001 Mar;16(3):169-73.

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Kozielec T, Starobrat-Hermelin B. Assessment of magnesium levels in children with attention deficit hyperactivity disorder (ADHD). Magnes Res. 1997 Jun;10(2):143-8.

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Lelord G, Callaway E, Muh JP. Clinical and biological effects of high doses of vitamin B6 and magnesium on autistic children. Acta Vitaminol Enzymol. 1982;4(1-2):27-44.

Liebscher DH, Liebscher DE. About the misdiagnosis of magnesium deficiency. J Am Coll Nutr. 2004 Dec;23(6):730S-1S.

Martineau J, Barthelemy C, Garreau B, Lelord G. Vitamin B6, magnesium, and combined B6-Mg: therapeutic effects in childhood autism. Biol Psychiatry. 1985 May;20(5):467-78.

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Mousain-Bosc M, Roche M, Rapin J, Bali JP. Magnesium VitB6 intake reduces central nervous system hyperexcitability in children. J Am Coll Nutr. 2004 Oct;23(5):545S-548S.

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Saavedra JM. Use of probiotics in pediatrics: rationale, mechanisms of action, and practical aspects. Nutr Clin Pract. 2007 Jun;22(3):351-65.

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Starobrat-Hermelin B, Kozielec T. The effects of magnesium physiological supplementation on hyperactivity in children with attention deficit hyperactivity disorder (ADHD). Positive response to magnesium oral loading test. Magnes Res. 1997 Jun;10(2):149-56.

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Toskes PP, et al. Vitamin B 12 malabsorption in chronic pancreatic insufficiency. N Engl J Med 1971 Mar 25;284(12):627-32.

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Autism and Detoxification back to top

Adams JB, Romdalvik J, Ramanujam V.M.S., Legator MS, Mercury, Lead, and Zinc in Baby Teeth of Children with Autism vs. Controls. J Toxicol Environ Health 2007 70(12):1046-51. 

Adams JB, Romdalvik J, Levine KE, Hu LW. Mercury in first-cut baby hair of children with autism versus typically developing children. Toxic Environ Chem. 2008, 1-14, iFirst.

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Aremu DA, Madejczyk MS, Ballatori N. N-acetylcysteine as a potential antidote and biomonitoring agent of methylmercury exposure. Environ Health Perspect. 2008 Jan;116(1):26-31.

Aschner M, Syversen T, Souza DO, Rocha JB. Metallothioneins: mercury species-specific induction and their potential role in attenuating neurotoxicity. Exp Biol Med (Maywood). 2006 Oct;231(9):1468-73.

Aw TY, Wierzbicka G, Jones DP. Oral glutathione increases tissue glutathione in vivo. Chem Biol Interact. 1991;80(1):89-97.

Aw TY. Intestinal glutathione: determinant of mucosal peroxide transport, metabolism, and oxidative susceptibility. Toxicol Appl Pharmacol. 2005 May 1;204(3):320-8.

Bello SC. Autism and environmental influences: review and commentary. Rev Environ Health 2007: 22(2): 139-56.

Beversdorf DQ, Manning SE, et al. Timing of prenatal stressors and autism. J Autism Dev Disord 2005: 35(4): 471-8.

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Desoto MC, Hitlan RT. Blood Levels of Mercury Are Related to Diagnosis of Autism: A Reanalysis of an Important Data Set. J Child Neurol. 2007 Nov;22(11):1308-1311.

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