Monday, 30 May 2016

Organic pollutants and behavioural severity in autism?



To get a few things straight first, this and other related research does not say that every diagnosis of autism is somehow the product of a 'toxic' exposure. Nor does it belittle the substantial contribution that genetics (whether structural or non-structural issues) confer when it comes to diagnosis. To my mind, it adds another level of complexity to the [various] hows and whys relating to how autism might come about [2]. That, and offering some important biologically-led guidance on what might be done to decrease any body load of such pollutants as and when they are detected and there's quite a bit we can learn from such studies.

Anyhow, Boggess et al started from the position of wanting to "evaluate the relationship between organic pollutants and behavioral severity in children with ASD [autism spectrum disorder] and matched controls." Thirty children diagnosed with autism were matched (age and sex) with 30 children without autism. Quite a panel of diagnostic and screening instruments were included as part of the study protocol, including ADOS (Autism Diagnostic Observation Schedule) and interestingly, the ATEC (see here). Each participant provided a blood sample, and the serum portion of the sample was subject to analysis by GC-MS (Gas Chromatography-Mass Spectrometry) for various compounds. Compounds included: "Three volatile organic compounds (VOC), benzene, toluene, and o-xylene; one alkane, hexane; five polychlorinated biphenyls (PCB), IUPAC congeners 28, 52, 101, 138, and 153; two polybrominated diphenylethers (PBDE), IUPAC congeners 47 and 99; two organochlorine pesticides, metolachlor and acetochlor; one dinitroanaline pesticide, pendimethalin; one organophosphate pesticide, chlorpyrifos; one phthalate, bis (2-ethylhexyl) phthalate (DEHP); and the chlorocarbon perchloroethylene."

Results: well, looking directly at the metabolites under inspection and comparing the group results (autism group vs control group) in terms of individual quantified levels, there seemed very little see. The only compound that was statistically significant in terms of amounts between the groups was something called metolachlor, a herbicide, which was actually found in higher mean concentrations in the control group than the autism group. When also researchers compared "the pooled mean of all compounds from the ASD cohort to the pooled mean for all compounds in the control cohort" they similarly noted no significant difference. At this point you're probably thinking that this isn't particularly interesting data. Well, just hold it there...

Researchers further examined whether there was something to see when comparing the mean xenobiotic body-burden (MXB) and those ADOS scores. Xenobiotic by the way, is another way of saying (foreign) compounds that were being assayed for, and combined with ADOS scores was a way of looking at whether behavioural severity might show some link to the concentrations of those compounds being reported on. In this respect: "Pooled serum-concentration correlated significantly with increasing behavioral severity on the ADOS in the ASD cohort... but not controls." The authors go on to say that such findings and others are "a fundamental expectation from the hypothesis of genetic predisposition for susceptibility to environmental triggers."

Some other points are raised in the Boggess paper not least those connected to the various biological mechanisms designed to metabolise such compounds and where they may fit with regards to some autism. Personally, I think this is where the money is eventually going to be; with further work required on processes linked to glutathione (see here) and more specific genetic-biological issues (e.g. PON1 [3]) potentially showing how genetic fragility and non-genetic factors might combine specifically when it comes to getting rid of various pollutants from the body.

There are methodological issues with the Boggess paper that do need to be mentioned not least the small participant group and the reliance on one blood sample showing a snapshot of current biology (combined with a snapshot of current behaviour). This last point in particular tells us little about any historical issues and whether there are important time-frames where environmental exposures might exert a more significant effect and the impact of any genetic issues. But, in the context of other research talking about environmental factors potentially being linked to autism (see here for example) it would be unwise to rule anything out just yet...


[1] Boggess A. et al. Mean serum-level of common organic pollutants is predictive of behavioral severity in children with autism spectrum disorders. Sci Rep. 2016 May 13;6:26185.

[2] Vijayakumar NT. & Judy MV. Autism spectrum disorders: Integration of the genome, transcriptome and the environment. Journal of the Neurological Sciences. 2016; 364: 167-176.


---------- Boggess A, Faber S, Kern J, & Kingston HM (2016). Mean serum-level of common organic pollutants is predictive of behavioral severity in children with autism spectrum disorders. Scientific reports, 6 PMID: 27174041