GI and autism studies ‘none of these trials appeared to be of high quality’

8 Feb

A new paper is due out soon looking at the available literature on GI and autism.

The significance of the association between many gastrointestinal (GI) pathologies and autism has yet to be discovered. The aim of the present study was to review available evidence documenting any link between autism and GI histopathology in children

I’ve only got the abstract to go by but even that is fairly damning.

Eight studies have reported the histopathological features of the GI tract in children with autism and fulfilled inclusion criteria. In general, none of these trials appeared to be of high quality. Apart from intestinal lymphonodular hyperplasia, the majority of these findings were not consistent….GI pathological findings in children with autism have been inconsistent. The present available evidence does not support or refute a link between GI histopathology and autism in children. The significance of intestinal lymphonodular hyperplasia in these children is unknown.

I’m hoping to get the full paper soon. It would be interesting to know what these eight studies were.

Update

Here’s the eight papers of low quality:

Furlano RI, Anthony A, Day R, et al. Colonic CD8 and gamma delta Tcell
infiltration with epithelial damage in children with autism. J Pediatr
2001;138:366–72.

Wakefield AJ, Anthony A, Murch SH, et al. Enterocolitis in children
with developmental disorders. Am J Gastroenterol 2000;95:2285–95.

Torrente F, Ashwood P, Day R, et al. Small intestinal enteropathy with
epithelial IgG and complement deposition in children with regressive
autism. Mol Psychiatry 2002;7:375–82. 34.

Ashwood P, Anthony A, Pellicer AA, et al. Intestinal lymphocyte
populations in children with regressive autism: evidence for extensive
mucosal immunopathology. J Clin Immunol 2003;23:504–17.

Ashwood P, Anthony A, Torrente F, et al. Spontaneous mucosal
lymphocyte cytokine profiles in children with autism and gastrointestinal
symptoms: mucosal immune activation and reduced counter regulatory
interleukin-10. J Clin Immunol 2004;24:664–73.

Wakefield AJ, Ashwood P, Limb K, et al. The significance of ileocolonic
lymphoid nodular hyperplasia in children with autistic spectrum
disorder. Eur J Gastroenterol Hepatol 2005;17:827–36.

Torrente F, Anthony A, Heuschkel RB, et al. Focal-enhanced gastritis in
regressive autism with features distinct from Crohn’s and Helicobacter
pylori gastritis. Am J Gastroenterol 2004;99:598–605.

14. DeFelice ML, Ruchelli ED, Markowitz JE, et al. Intestinal cytokines in
children with pervasive developmental disorders. Am J Gastroenterol
2003;98:1777–82.

No surprises there.

10 Responses to “GI and autism studies ‘none of these trials appeared to be of high quality’”

  1. esattezza February 9, 2011 at 00:17 #

    Who are the authors, Kev? I want to add it to my NCBI alerts.

  2. Astrid February 9, 2011 at 12:38 #

    Wakefield as co-author for several of these studies. That should send a a lightbulb to the reviewers anyway. Note that most studies were done by roughly the same author group. In conclusion, a small number of questionnable researchers believe that autism is associated with GI pathology.

  3. esattezza February 9, 2011 at 22:20 #

    I’d actually meant the authors of the upcoming review, but this is good too.

  4. Berthajane Vandegrift February 9, 2011 at 22:35 #

    Autism may have many causes, but both of my sons had GI problems. One is autistic and the other is a physicist. I do suspect autism is merely a non conformist personality. Children who do not develop enough learning ability to compensate for their lack of intuitive knowledge are called autistic. Others, like my older son, become physicists. And I see no reason to regard becoming a physicist as an abnormality. My story can be read on line at
    A Few Impertinent Questions about Autism, Freudianism and Materialism
    http://30145.myauthorsite.com

    • Sullivan February 9, 2011 at 23:04 #

      “Children who do not develop enough learning ability to compensate for their lack of intuitive knowledge are called autistic. Others, like my older son, become physicists.”

      And, there are physicists (and other scientists) who are also autistic.

  5. passionlessDrone February 10, 2011 at 01:00 #

    Hello friends –

    It seems that a lack of specificity is occurring within this thread; namely extrapolating out a relative paucity of studies involving histopathology within the GI tract, with GI problems in general. In other words, there are only a few studies that have directly sampled tissue from people with autism from the GI tract and found abnormalities, and of those, different consistency in findings.

    That being said, there are some other reasons to think that GI disturbances in children with autism are real; not necessariliy causative, and not in every child with autism, but still not imaginary.

    Alterations of the intestinal barrier in patients with autism spectrum disorders and in their first-degree relatives tested 90 children with autism and their relatives and found:

    A high percentage of abnormal IPT values were found among patients with autism (36.7%) and their relatives (21.2%) compared with normal subjects (4.8%). Patients with autism on a reported gluten-casein-free diet had significantly lower IPT values compared with those who were on an unrestricted diet and controls. Gastrointestinal symptoms were present in 46.7% of children with autism: constipation (45.5%), diarrhoea (34.1%), and others (alternating diarrhoea/constipation, abdominal pain, etc: 15.9%). FC was elevated in 24.4% of patients with autism and in 11.6% of their relatives; it was not, however, correlated with abnormal IPT values

    None of the children had celiac, and the sample size is more than twice the two negative studies in this regard combined. While this study did not technically measure tissue, it was more of a measure of tissue permiabililty by proxy, it still speaks towards intestinal function.

    Similarly, the very hihgly replicated findings of MET alleles in autism has found that people with autism, and the MET C allele have higher incidences of gastro problems.

    Distinct genetic risk based on association of MET in families with co-occurring autism and gastrointestinal conditions

    In the entire 214-family sample, the MET rs1858830 C allele was associated with both autism spectrum disorder and gastrointestinal conditions. Stratification by the presence of gastrointestinal conditions revealed that the MET C allele was associated with both autism spectrum disorder and gastrointestinal conditions in 118 families containing at least 1 child with co-occurring autism spectrum disorder and gastrointestinal conditions. In contrast, there was no association of the MET polymorphism with autism spectrum disorder in the 96 families lacking a child with co-occurring autism spectrum disorder and gastrointestinal conditions. chi(2) analyses of MET rs1858830 genotypes indicated over-representation of the C allele in individuals with co-occurring autism spectrum disorder and gastrointestinal conditions compared with non-autism spectrum disorder siblings, parents, and unrelated controls.

    The protein produced by the MET gene does lots of stuff that you’d expect an autism risk gene to do in the CNS, but also plays a part in gastrointestinal repair. Unless we want to discount the MET studies, and there are a lot of them, or find reasons that HGF isn’t playing a part in gastrointestinal repair in the autism subgroup in particular, these findings make a lot of sense, regardless of conflicting histological studies.

    There is a persistent, and to my mind, curious desire to place all complaints of gastrointestinal problems in autism at Wakefields feet, and as such, declare them void. I think the reality is that we have a lot left to learn.

    – pD

  6. esattezza February 10, 2011 at 01:23 #

    @pD Yeah… Wakefield did a huge disservice to certain segments of autism research (ex: non-neuro comorbidities, environmental trigers). I actually wrote up my first Qualifying exam proposal (first big test in grad school) based on the MET gene, but it was rejected. It’s too controversial, aka too risky, aka unlikely to be funded. I think it’s fascinating and I’d bet that we’d see definitive links between ASD and GI symptoms if we looked specifically in people with a mutation in the MET pathway. And I can certainly understand how treating GI symptoms in those children (not specifically treating the MET mutation, just simply treating the symptoms) might improve autism symptoms. You’re right, it’s certainly unlikely that GI problems cause autism, but it’s easy to see how the pain and frustration at not being able to communicate it can make ASD symptoms worse.

  7. sharon February 10, 2011 at 04:49 #

    I see no reason, as outlined above, to question that some Autists will also have GI issues, just as some have Epilepsy, ADHD, OCD and so on. Non causative, yet co morbid (to use an unfortunate term)

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