Urine test for autism? Hmmm

4 Jun

Following on from Lisa Jo’s well placed concerns about this study,I also have a few. Namely the references. Not being scientifically qualified to tackle the meat of the paper I look straight at what the researcher uses to support his ideas. So far I’ve found these references the authors base their paper on:

1) Kidd, P. M. Autism, an extreme challenge to integrative medicine. Part: 1: The knowledge base. Altern. Med. Rev. 2002, 7 (4), 292–316.

2) Ashwood, P.; Anthony, A.; Pellicer, A. A.; Torrente, F.; Walker-Smith, J. A.; Wakefield, A. J. Intestinal lymphocyte populations in children with regressive autism: evidence for extensive mucosal immunopathology. J. Clin. Immunol. 2003, 23 (6), 504–17.

3) Bolte, E. R. Autism and Clostridium tetani. Med. Hypotheses 1998, 51 (2), 133–44

4) James, S. J.; Cutler, P.; Melnyk, S.; Jernigan, S.; Janak, L.; Gaylor, D. W.; Neubrander, J. A. Metabolic biomarkers of increased oxidative stress and impaired methylation capacity in children with autism. Am. J. Clin. Nutr. 2004, 80 (6), 1611–7

At the very least, relying on studies from Alternative Medical Review, studies co-authored by Andrew Wakefield, studies from Medical Hypothesis and studies co-authored by Jim Neubrander should give rise to questions over the credibility of this paper. Is it enough to scupper it? Of course not. But when we take Lisa Jo’s questions into the bargain – that autism does not always, if ever, have a distinct GI component, I have to wonder about this paper.

19 Responses to “Urine test for autism? Hmmm”

  1. Broken Link June 4, 2010 at 17:16 #

    Kev, I’ve read the paper. The first thing that is clear is that they do not talk at all about what might be different in the diets of the children with ASD, compared to their siblings and the typical controls. One obvious thing may be that the kids with ASD are on a special diet, e.g. GFCF diet. Another possibility is that they are on extra dietary supplements. Any of these things might be expected to influence the chemicals found in their urine (what goes in influences what goes out). I would have expected to see some kind of mention if the authors had taken the ASD kids off supplements and/or special diets before collection the samples, so I assume they did not.

    The Australian author, Manya Angley is the author of a paper on the use of complementary and alternative medicines in ASD, so she is fully aware of how common this is. So, it’s surprising to me that there is no mention at all of this probable confound.

  2. Tsu Dho Nimh June 4, 2010 at 18:06 #

    Unless they had all three groups of children on a standardized diet for a week or so before they took the samples, it means nothing.

  3. Laurent June 4, 2010 at 18:29 #

    This track is not exactly new:
    “Differences between the gut microflora of children with autistic spectrum disorders and that of healthy children”

    There is more one type of autism, more one sub-type of autism; a unique test for all the spectrum seems highly improbable.

    Perinatal problems with bacteria maybe be one cause of autism and if this is true maybe in this case bacteria can let markers.

    So, if you want to make money with a valid or unvalid test, this is a good idea, the market is ready.

  4. Regan June 4, 2010 at 21:47 #

    I thought this article did a careful job of summing up some of the limitations and caveats on what was looked at in relation to what was reported,

  5. Tsu Dho Nimh June 4, 2010 at 22:59 #

    I’ve been down that route in analytical chemistry – when you start slicing and dicing with statistical analysis of substances with complex chemical makeup and fancy lab equipment you can almost always find some spot that seems to give you the answer you are looking for.

    Here’s the real test. Can they take urine samples from other children, some autistic, some not, some siblings of autistics, repeat their analysis, look at the “fingerprint” and correctly identify which samples came from which group?

    If not, they don’t have a test.

  6. KWombles June 4, 2010 at 23:01 #

    I also dug into the article and pulled the articles used to bolster the gut disturbance argument and went through them.

  7. Joseph June 4, 2010 at 23:04 #

    Plausibility is one thing, and I don’t know if it is or isn’t plausible.

    In the end, though, the most important thing is whether the test actually works. This is where it gets problematic. The authors don’t say what the sensitivity and specificity of the test is. They apparently don’t consider the possibility of overfitting. What did they do to make sure the test generalizes to other populations? Apparently nothing. Note that the sample size is relatively small, and they looked at many measures.

    In other words, given that they didn’t double-check themselves, it’s hard to tell if it actually works without an independent reproduction of these results.

  8. Laurent June 5, 2010 at 09:59 #

    There is a good analysis here:

  9. Science Mom June 5, 2010 at 14:30 #

    Countdown to when this ‘test’ will show up on the standard DAN! panel of dubious tests. Accompanied by, of course, a ‘treatment’ regime.

  10. Brainduck June 7, 2010 at 19:28 #

    Actually, the paper does specify that the children weren’t on vitamins.

    Been discussing this over here if you’d like to join in: http://www.badscience.net/forum/viewtopic.php?f=3&t=16572&p=371502#p371417

    IMO it’s a potentially interesting-to-researchers study, but the between-groups differences are overwhelmed by individual variations. Trying to diagnose ASD on this basis would be like trying to diagnose gender based on height. The headlines are wrong, but the study could be interesting anyway.

  11. Broken Link June 7, 2010 at 20:16 #

    Thanks Brainduck, I missed that – was expecting the lack of vitamins to be mentioned in the Methods, rather than in the Discussion. And it is strangely worded: “The differences observed in these metabolite concentrations cannot be explained simply by intake of exogenous compounds since the samples used in
    the data analysis were preselected from individuals, who were
    reported not to have taken vitamin supplements.”

    What does that mean – “samples used in data analysis were preselected” – does that imply that some of the samples were dropped from the data analysis?

    Also very interesting that the siblings are closer to the ASD results than to the controls – could be the siblings are on partial or full GFCF diets, while the controls aren’t. I think it’s very common for parents to reduce the gluten and casein for the whole family, while being just a more strict with the child with ASD.

  12. Joseph June 7, 2010 at 20:36 #

    Trying to diagnose ASD on this basis would be like trying to diagnose gender based on height.

    It’s more like trying to diagnose gender based on written text, which — you’d be surprised — is doable with at least 70% accuracy.

  13. Brainduck June 7, 2010 at 20:40 #

    Given ‘broad phenotype’ processing differences in relatives of people with ASD, I would be surprised if there weren’t some differences in any underlying biochemistry in siblings, too.

    Of course, siblings are likely to have more similar gut bacteria than unrelated people in another country, whether or not they have ASD.

  14. Joseph June 8, 2010 at 01:23 #

    The “gut bacteria” stuff appears to be complete speculation in the part of the authors of the study. They probably just thought it goes to plausibility. All they are doing is comparing urine spectra — and I don’t believe you can detect bacteria in urine spectra.

    BTW, I bet you can theoretically classify gender with urine, and I bet it’s a heck of a lot easier.

  15. Science Mom June 8, 2010 at 05:20 #

    All they are doing is comparing urine spectra—and I don’t believe you can detect bacteria in urine spectra.

    Correct, you can’t directly detect microbiota in urine with the equipment they used, they were testing for co-metabolites or bacterial products that would be present in urine. The problem is, is that they didn’t control for anything such as diet, supplements and environmental exposure. Their comparison of Swiss and Australian children would also confound the data. An interesting vein of research but very poorly done and very over-reaching conclusions in the press release.


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