By John Stone
May 14, 2010
For six years Sunday Times journalist Brian Deer has been trying to kid us
that three experienced gastroenterologists liaising with other professionals
within and beyond the walls of the Royal Free Hospital in North London ordered
invasive procedures children without significant GI issues. In this short
article, originally published as a letter in BMJ Rapid Responses Lorene Amet and
Pippa Line of the UK’s
Autism Treatment Trust demonstrate just how implausible and tenuous Deer’s
Brian Deer’s article questions the existence of “autistic enterocolitis” in the ‘Lancet’ children (link: HERE). The letter from Drs McClure and O’Hare (link:HERE) questions the validity of the autism diagnosis of the same children. How long before someone pops up and questions the children’s very existence? It would appear these children are an inconvenience in this heavily charged debate.
Notwithstanding, questioning the accuracy of an autism diagnosis is always very pertinent and needs to be properly addressed. Autism spectrums disorders (ASD) comprise a heterogeneous spectrum of developmental conditions that include autism, Asperger Syndrome and pervasive developmental disorder not otherwise specified (PDD-NOS). The diagnosis is based on the detailed assessment of the individual’s communication, social, behavioural and developmental presentation. In the last three decades, however, numerous peer-reviewed studies have shown that ASD can be associated with a great variety of unrelated aetiologies of a genetic and/or environmental nature (1). The psychiatric presentation of individuals is therefore important (2) but insufficient to understand and define this heterogeneous group of developmental disorders.
Importantly, children with chronic gut problems are more likely to present
with hyperactivity (÷2 (1) = 9.665, p = .002, this is reflected by the odds
ratio whereby those with current gut problems were 2.33 times more likely to
have hyperactivity than those without), sleep issues (÷2 (1) = 6.649, p = .010,
this is reflected by the odds ratio whereby those with gut problems were 1.96
times more likely to have sleep problems than those without) and abnormal fits
of crying spells, occurring suddenly and even at night time (÷2 (1) = 5.075, p =
.024, this is reflected by the odds ratio whereby those with current gut
problems were 1.80 times more likely to have crying problems than those
without). Developmentally, these children are also more likely to have
experienced regressive autism, characterised by a loss of acquired developmental
skills in the areas of communication and socialisation and to present with novel
deviant restricted and repetitive behaviours (÷2 (1) = 5.619, p = .018, this is
reflected by the odds ratio whereby those with current gut problems were 1.93
times more likely to have regression than those without). In terms of markers,
20% of children presenting with chronic gut issues have abnormal levels of
faecal calprotectin, a surrogate marker of Inflammatory Bowel Disease
characterised by pathological inflammation of the bowel wall (5). These findings
indicate that the gastro-intestinal problems encountered in autism are related
to a range of behavioural and developmental abnormalities, and are associated
with markers of inflammation, consistent with other reports (6-8). These are
therefore likely to be central to the dysfunction experienced by this sub-set of
Children with autism also commonly present with severe chronic immune problems (observed in 65% of a group of 258 children with autism at the ATT clinic). These include eczema (24%), repetitive chronic and long- lasting infection issues (36%), food and/or inhalant allergies (37%), asthma (7%). A significant association between children presenting with immune problems and those with parental immune problems was found indicating a common genetic susceptibility (÷2 (1) = 5.543, p = .013, this is reflected by the odds ratio whereby those with immune problems were 1.86 times more likely to have parents with immune problems than those without). Additionally, there was also a significant association between immune problems and self- injurious behaviour (÷2 (1) = 4.152, p = .028, this is reflected by the odds ratio whereby those with immune problems were 1.85 times more likely to have self-injurious behaviour than those without). In terms of markers, a surrogate marker for cell immunity called neopterine (9) was found to statistically correlate with isoprostane (10), a marker of oxidative stress (r =0.547, p (one- tailed) <.001. The R2 value of .299 indicates that the markers account for 30% of the variation in the levels of each other). Both immune and oxidative stress-issues have been reported to be centrally associated with a sub-set autism (11-12).
In conclusion, autism spectrum disorders include a range of syndromes characterised by varying degrees of clinical, developmental and behavioural symptoms. It is essential to provide a systematic evaluation of affected individuals in order to address the range of abnormalities identified. Autistic individuals have suffered greatly due to internal medical politics. It is time to move on.
1. Gillberg, C. and Coleman, M. 2000. The biology of the autistic syndromes. Cambridge University Press.
2. Iain McClure, Anne O'Hare (28 April 2010). How can we be confident that the children with "autistic enterolcolitis" have autism? Rapid response BMJ 2010:340.
3. Deer B. Wakefield’s ‘autistic colitis’ under the microscope. BMJ 2010; 340: 838-41.
4. Buie T, Fuchs GJ 3rd, Furuta GT, et al. 2010. Recommendations for evaluation and treatment of common gastrointestinal problems in children with ASDs. Pediatrics. Jan;125 Suppl 1:S19-29.
5. Costa F, Mumolo MG, Ceccarelli L, Bellini M, Romano MR, Sterpi C, Ricchiuti A, Marchi S, Bottai M..Calprotectin is a stronger predictive marker of relapse in ulcerative colitis than in Crohn's disease. Gut. 2005 Mar;54(3):364- 8.
6. Ashwood, P., Anthony, A., Pellicer, A.A., et al. 2003. Intestinal lymphocyte populations in children with regressive autism: evidence for extensive mucosal immunopathology. Journal of Clinical Immunology, 23:504- 517.
7. Krigsman, A., Boris, M., Goldblatt, A., and Stott. C. Clinical Presentation and Histologic Findings at Ileocolonoscopy in Children with Autistic Spectrum Disorder and Chronic Gastrointestinal Symptoms. Autism Insights 2009:1 1– 11.
8. Balzola, F., Barbon V., Repici, A., Rizzetto, M., Clauser, D., Gandione, M., and Sapino, A. Panenteric IBD-like disease in a patient with regressive autism shown for the first time by wireless capsule enteroscopy: Another piece in the jig-saw of the gut-brain syndrome American Journal of Gastroenterology, 2005. 100(4): p. 979- 981.
9. Sweeten, T.L., Posey, D.J. and McDougle, C.J. High blood monocyte counts and neopterin levels in children with autistic disorder. Am. J. Psychiatry 2003:160, 1691-1693.
10. Wu X, Cai H, Xiang YB, Cai Q, Yang G, Liu D, Sanchez S, Zheng W, Milne G, Shu XO. Intra-person variation of urinary biomarkers of oxidative stress and inflammation. Cancer Epidemiol Biomarkers Prev. 2010 Apr;19(4):947-52. Epub 2010 Mar 23.
11. Vargas, D.L., Nascimbene, C., Krishnan, C., et al. 2005. Neuroglial activation and neuroinflammation in the brain of patients with autism. Ann. Neurol. 57(1):67-81.
12. Sweeten, T.L., Bowyer, S.L., Posey, D.J., Halberstadt, G.M., and McDougle,C.J. Increased prevalence of familial autoimmunity in probands with pervasive developmental disorders. Pediatrics 2003:112(5):e420.
John Stone is UK Editor for Age of Autism.