Volatile organic compounds and autism

As harsh as the phrase volatile organic compounds (VOCs) might appear at first glance, all this refers to is a class of compounds containing carbon which have a tendency to evaporate at room temperature assuming normal air pressure. VOCs have been associated with pollutants as per their inclusion in various literature on the topic of things like indoor air pollution (see here) and the fact that just about everything around us in the modern home or office is likely to release VOCs. Whilst not trying to belittle the potential effects of some of those VOCs (see here) it is important to note however that living things also produce and release VOCs [1] as by-product of metabolism too.

The reason for the chatter about VOCs in today's post relates to a paper by Rosaria Cozzolino and colleagues [2] and their preliminary advances into investigating whether VOCs might have some potential as biomarkers for the autism spectrum disorders (ASDs). In amongst the authorship list on the Cozzolino paper I also note a familiar name - Laura de Magistris - who some people might recognise as being the lead on some of that very interesting leaky gut work (see here).

A few details from the paper first:

• Regular readers on this blog might already know that I like talking about analytical chemistry, particularly when applied to autism or other potentially related conditions. In the case of the Cozzolino paper it was all about preparing urine samples from 24 children with autism and 21 asymptomatic controls via something called solid-phase extraction, sorry, solid-phase microextraction (SPME) and then applying the solute to analysis via gas chromatography - mass spectrometry (GC-MS) "to obtain metabolomic information patterns". Metabolomics by the way, is basically the collected analysis of small molecules (metabolites) in one or more biofluids.
• Following some discriminant function analysis (DFA) of results from both groups prepared under both acid and alkaline conditions, authors presented quite a bit of data on what compounds, VOCs, might have some discriminatory function between the autism (A) group and the control (C) group. So: "Among these [compounds], 3-methyl-cyclopentanone, 3-methyl-butanal, 2-methyl-butanal, and hexane under acid conditions, and 2-methyl-pyrazine, 2,3-dimethyl-pyrazine, and isoxazolo under alkaline pH had statistically higher levels in urine samples from autistic children than from the control group".
• Authors suggested quite a bit more analysis might be needed to look at the "metabolic origins of these variables" and "verify the usefulness... for early-stage [autism] diagnosis".

I know, I know. Mention of the word 'biomarker(s)' when it comes to such a heterogeneous and possibly plural condition like 'the autisms' is still something rather problematic as things currently stand. I'm not saying that there may not be specific types of autism (endophenotypes) which might be amenable to certain biomarkers such as VOCs, but I don't quite think we are there yet in determining the hows and whys. And then there are the very small participant numbers reported on by Cozzolino et al...

But this is not the first times that VOCs have turned up in autism research. The paper by De Angelis and colleagues [3] (open-access) talked about levels of VOCs detected in poop samples being "markedly affected in PDD-NOS [Pervasive Developmental Disorder Not Otherwise Specified ] and, especially, AD [autism] children". Stool analysis and the gut microbiome, as regular readers of this blog might know, is of increasing interest to autism research.

Keeping in mind discussions on VOCs in relation to [some?] autism, I'll also introduce the paper by Kalkbrenner and colleagues [4] which, following a review of the some of the literature on environmental chemical (yes, that word again) exposures and autism, suggested that there may be more to see when it comes to specific environmental factors. So: "some environmental exposures showed associations with autism, especially traffic-related air pollutants, some metals, and several pesticides, with suggestive trends for some volatile organic compounds (e.g., methylene chloride, trichloroethylene, and styrene) and phthalates". This on the back of previous research from this author on this topic [5].

Accepting that VOCs cover a whole slew of different compounds and that not every VOC has been analysed with an autism link (or not) in mind, the various papers hint that we should be a little more wary of this class of compounds and perhaps a little more inquisitive when it comes to a condition like autism.

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[1] Shirasu M. & Touhara K. The scent of disease: volatile organic compounds of the human body related to disease and disorder. J Biochem. 2011 Sep;150(3):257-66.

[2] Cozzolino R. et al. Use of solid-phase microextraction coupled to gas chromatography–mass spectrometry for determination of urinary volatile organic compounds in autistic children compared with healthy controls. Analytical & Bioanalytical Chemistry. 2014. 10.1007/s00216-014-7855-z

[3] De Angelis M. et al. Fecal microbiota and metabolome of children with autism and pervasive developmental disorder not otherwise specified. PLoS One. 2013 Oct 9;8(10):e76993.

[4] Kalkbrenner AE. et al. Environmental Chemical Exposures and Autism Spectrum Disorders: A Review of the Epidemiological Evidence. Curr Probl Pediatr Adolesc Health Care. 2014 Sep 4. pii: S1538-5442(14)00074-1.

[5] Kalkbrenner AE. et al. Perinatal exposure to hazardous air pollutants and autism spectrum disorders at age 8. Epidemiology. 2010 Sep;21(5):631-41.

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Cozzolino R, De Magistris L, Saggese P, Stocchero M, Martignetti A, Di Stasio M, Malorni A, Marotta R, Boscaino F, & Malorni L (2014). Use of solid-phase microextraction coupled to gas chromatography-mass spectrometry for determination of urinary volatile organic compounds in autistic children compared with healthy controls. Analytical and bioanalytical chemistry, 406 (19), 4649-62 PMID: 24828982



Kalkbrenner AE, Schmidt RJ, & Penlesky AC (2014). Environmental Chemical Exposures and Autism Spectrum Disorders: A Review of the Epidemiological Evidence. Current problems in pediatric and adolescent health care PMID: 25199954