Friday, 19 July 2013

Autism, gut problems and oxidative stress

I'm still a rank amateur when it comes to talking about many aspects of autism research. Mitochondrial dysfunction remains a particularly curious area of research to me as I might have mention previously, but other areas are equally as baffling.
Storm in a teacup @ Wikipedia 

Take for example oxidative stress and the various research done on this topic in connection to autism. Yes, I've touched upon some aspects of this wide, very wide, area of investigation in previous posts (see here and here) but still it's hard going for me and I don't mind admitting it.

I therefore approach the paper by Phillip Gorrindo and colleagues* (open-access) with some degree of trepidation, and their suggestion that the presence of gastrointestinal (GI) issues appearing alongside cases of autism might very well be implicated in the whole oxidative stress area.

Some of you might remember the name Phillip Gorrindo and the excellent study** he was involved with suggesting that when mums and dads of children with autism talk about GI or bowel problems presenting in their children, professionals may do well to listen to them rather than fobbing them off as merely being 'non-experts'. By saying this I'm implying that parents are partners when it comes to identifying such issues as they are in other areas.

In this latest paper - which again has some media attention attached to it - we are told of three reasons why the authors chose to look at autism, GI issues and oxidative stress based on (i) the gut and brain possessing a "likely shared susceptibility to insults", (ii) that old mitochondrial ticket (see here again), and (iii) the links already made between autism and oxidative stress. The inclusion of the GI bit stems, I assume, from the previous focus of the author's work and quite a large volume of other research looking at GI issues and oxidative stress (see here for example) outside of autism.

So:
  • Four groups of participants were included for study: ASD+GI issues (n=27), ASD alone (n=29), GI issues with no ASD (n=21) and an "unaffected" group (n=10). GI issues by the way, were defined as functional GI issues (constipation, reflux, IBS, abdominal pain).
  • Blood samples were provided by participants and plasma levels of F2-Isoprostanes were analysed blind via GC-MS (although not seemingly based on accurate mass). 
  • In addition, levels of plasma triglycerides were also measured explained due to the effects of blood lipids on F2-IsoPs.
  • Results: well, in all clinical groups, including the GI issues only group, mean levels of F2-IsoPs were above that seen in the unaffected control group.
  • Group levels of F2-IsoPs were significantly greater in the ASD+GI group compared with the ASD alone group (p=0.007), although the ASD+GI group and GI issues with no ASD group were not significantly different from one and another.
  • Plasma triglyceride measurements also suggested that compared to the unaffected control group, the other groups all presented with elevations.
  • As well as looking at just the biochemistry side of things, the authors also noted that when it came to looking at "social impairment", the ASD+GI group seemed to fare considerably worse than the other groups.
  • The authors conclude that: "individuals with co-occurring ASD and GID [gastrointestinal dysfunction] may exhibit clinical phenotypes that are sufficiently distinct from children with ASD".

There's little more for me to add to this entry that has not already been said. Yes, the participant numbers were on the small side and so one has to be careful not to make too many sweeping generalisations. That being said though this is not the first time that such biochemical findings have been noted in cases of autism**. Quite by coincidence, I also stumbled across this recent paper by Ghezzo and colleagues*** (open-access) and this paper by Signorini and colleagues**** (open-access) both of which mention the isoprostanes (the Signorini paper with Rett syndrome in mind too). Isoprostanes with autism or autistic behaviours in mind seem to be rising in importance and with it their link to oxidative stress (see here).

I personally would have liked to have seen other markers linked to oxidative stress and its defences also measured and reported in this study. That very big elephant in the room that is glutathione is perhaps an important marker for future work in this area. I happened also to stumble across this article by Sido and colleagues***** (open-access) which talked about glutathione and inflammatory bowel disease (IBD) which might very possibly be relevant to those cases of autism where functional GI issues are part and parcel of something altogether more complicated (see here). Indeed the focus in the Sido article on cysteine brings us back to another important, if slightly under-rated, autism research avenue: sulphate (or sulfate if you wish).

To close, some music from Sonic Youth: 100% and some background on Joe.

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* Gorrindo P. et al. Enrichment of Elevated Plasma F2t-Isoprostane Levels in Individuals with Autism Who Are Stratified by Presence of Gastrointestinal Dysfunction. PLoS ONE 8(7):2013;  e68444. doi:10.1371/journal.pone.0068444

** Ming X. et al. Increased excretion of a lipid peroxidation biomarker in autism. Prostaglandins Leukot Essent Fatty Acids. 2005 Nov;73(5):379-84.

*** Ghezzo A. et al. Oxidative Stress and Erythrocyte Membrane Alterations in Children with Autism: Correlation with Clinical Features. PLoS One. 2013 Jun 19;8(6):e66418.

**** Signorini C. et al. Isoprostanes and 4-Hydroxy-2-nonenal: Markers or Mediators of Disease? Focus on Rett Syndrome as a Model of Autism Spectrum Disorder. Oxid Med Cell Longev. 2013;2013:343824.

**** Sido B. et al. Impairment of intestinal glutathione synthesis in patients with inflammatory bowel disease. Gut. 1998 Apr;42(4):485-92.

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ResearchBlogging.org Gorrindo P (2013). Enrichment of Elevated Plasma F2t-Isoprostane Levels in Individuals with Autism Who Are Stratified by Presence of Gastrointestinal Dysfunction PLoS ONE DOI: 10.1371/journal.pone.0068444