Monday, 2 February 2015

Bisphenol A Exposure in Children With Autism

The paper by T. Peter Stein and colleagues [1] suggesting an "association" between BPA (Bisphenol-A) and autism spectrum disorder (ASD) was always bound to create some interest. Reporting results based on the analysis of urine samples from a group of children diagnosed with an autism spectrum disorder (ASD) (n=46) compared to controls (n=52), authors concluded that: "there is an association between BPA and ASD." Association... note that word.
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BPA has been around for quite a few years. An important chemical in the production of certain plastics and resins, in more recent times quite a volume of science has suggested that caution should be applied to the use of and exposure to BPA particularly with reference to its potential estrogenic properties [2]. As with everything in life, the effects or not of BPA continue to be the source of some discussion, with concerns even been raised about the alternatives to BPA (see here) being put forward. In short, it's very, very complicated.

Stein and colleagues started from the premise that: "The major pathway for BPA metabolism and excretion is via glucuronidation." Glucuronidation involves the addition of glucuronic acid to a particular metabolite thus aiding the removal of said metabolite from the body. Those of you who have come across the whole sulphation and autism story might remember how glucuronidation and sulphation share some history with [some] autism in mind as per papers like the one from Alberti and colleagues [3]. Stein et al have some research form when it comes to glucuronidation and autism as per papers such as this one [4] (open-access) that concluded that: "The glucuronidation pathway may differ in some children with ASD." They reported lower levels of glucuronidation which impacted on the metabolism of phthalates among other things (see here).

Anyhow, the analytical weapon of choice in the BPA-autism study by Stein et al was mass spectrometry (MS). Again, this research group have some interest/experience in this area as per other research of theirs which has crossed my blogging path (see here). Looking at those urine samples from participants with ASD vs asymptomatic controls, researchers reported a few important details including that: "about 20% of the ASD children had BPA levels beyond the 90th percentile (>50 ng/mL) of the frequency distribution for the total sample of 98 children." They also reported "significant differences (P < 0.05) between the groups in total and % bound BPA" (bound BPA referring to BPA glucuronide). Reiterating their conclusion: "The results suggest there is an association between BPA and ASD."

Bearing in mind how the word 'chemical' has been mis-represented down the years, there is quite a body of work emerging suggestive that there is quite a bit more to do when it comes to environmental exposures potentially linking into at least some cases of autism. This is not the first time that BPA has been examined with autism in mind as per discussions like the one from de Cock and colleagues [5] and some animal model work such as that from Wolstenholme et al [6]. The paper from Kaur and colleagues [7] suggesting that: "BPA may act as an environmental risk factor for autism in genetically susceptible children by inducing oxidative stress and mitochondrial dysfunction" offers some tantalising areas of further research tallying with other non-autism research [8]. I might also bring your attention to the paper by Lichtensteiger and colleagues [9] (thanks to @autismepi) perhaps providing another important area for further research.

Further study is of course implied from the Stein work and other research in this area. That and quite a bit more investigation of the biological systems implicated in any effect from BPA on cases of autism brings the focus back to a model of genes and environment [variably] interacting on the very wide autism spectrum...

Music: Madonna - Papa Don't Preach. Well, preaching is what we do best!

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[1] Stein TP. et al. Bisphenol A Exposure in Children With Autism Spectrum Disorders. Autism Research. 2015. Jan 13.

[2] Sharpe RM. Is it time to end concerns over the estrogenic effects of bisphenol A? Toxicol Sci. 2010 Mar;114(1):1-4.

[3] Alberti A. et al. Sulphation deficit in "low-functioning" autistic children: a pilot study. Biol Psychiatry. 1999 Aug 1;46(3):420-4.

[4] Stein TP. et al. Autism and Phthalate Metabolite Glucuronidation. J Autism Dev Disord. Nov 2013; 43(11): 2677–2685.

[5] de Cock M. et al. Does perinatal exposure to endocrine disruptors induce autism spectrum and attention deficit hyperactivity disorders? Review. Acta Paediatr. 2012 Aug;101(8):811-8.

[6] Wolstenholme JT. et al. Gestational exposure to low dose bisphenol A alters social behavior in juvenile mice. PLoS One. 2011;6(9):e25448.

[7] Kaur K. et al. Bisphenol A induces oxidative stress and mitochondrial dysfunction in lymphoblasts from children with autism and unaffected siblings. Free Radic Biol Med. 2014 Nov;76:25-33.

[8] Veiga-Lopez A. et al. Impact of Gestational Bisphenol A on Oxidative Stress and Free Fatty Acids: Human Association and Interspecies Animal Testing Studies. Endocrinology. 2015. Jan 20.

[9] Lichtensteiger W. et al. Differential Gene Expression Patterns in Developing Sexually Dimorphic Rat Brain Regions Exposed to Anti-androgenic, Estrogenic, or Complex Endocrine Disruptor Mixtures: Glutamatergic Synapses as Target. Endocrinology. 2015 Jan 21: en20141504.

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ResearchBlogging.org Stein, T., Schluter, M., Steer, R., Guo, L., & Ming, X. (2015). Bisphenol A Exposure in Children With Autism Spectrum Disorders Autism Research DOI: 10.1002/aur.1444