Saturday, 13 August 2011

Polybrominated diphenyl ethers (PBDEs) and autism

The beautiful game of football (soccer) is a bit of national obsession here in the UK. In the bracing North-East of England, we have a particularly loyal following of fans who, every Saturday (or thereabouts) dress up in either red and white or black and white depending on their affinity to the Black Cats or the Magpies, and brave the elements to watch 90 minutes of sporting battle. Derby days when the two teams meet are something else!

I myself, whilst an interested follower of one of these teams (not saying which!), have never been as overly enthusiastic as some of my fellow North-Easterners, instead preferring to follow a different kind of sport, research. Funny you might think that he equates research with football, but it follows very similar principles: competition, goals, star players, money, esteem. Some would say that football is a matter of life or death; research is perhaps in some cases even more about life or death.

Within the autism research football division, several teams compete. At the moment, I would probably say that the team based at the UC Davis MIND Institute are the Manchester United of the Premier League. Indeed various papers from the MIND Institute have been covered on this blog. Their focus on the environmental as well as the genetic is perhaps what makes the MIND Institute stand out from the rest.

Why the long-winded introduction?

Well a paper has appeared recently which whilst outside of autism research could potentially tie into some areas covered by the MIND Institute team. The paper by Zota and colleagues* reports on a study looking at polybrominated diphenyl ethers (PBDEs) and related metabolites used as flame retardant materials alongside markers of thyroid function in pregnant mums based in California.

Many things contain PBDEs despite such compounds being banned in several parts of the world. Plastics, wire insulation, old furniture foam - much like asbestos, being banned does not necessarily mean that people are not exposed to such compounds (and for years after). Zota and colleagues sought to measure serum concentrations of PBDEs in mums-to-be who were in the second trimester of pregnancy. They found some of the highest concentrations of PBDE-related metabolites ever reported in pregnant women. Added to that they reported associations between PBDE findings and moderators of thyroid function such as thyroid-stimulating hormone (TSH).

Whilst it is not possible to say what specific effects such serum PBDE levels might have on the developing foetus bearing in mind their toxicity profile, it is fair to say that any potential disruption to maternal thyroid function caused by alterations in TSH levels is not likely to be good for the child. Foetal premature birth, low birth weight and even miscarriage and stillbirth have been noted in cases of gestational maternal hyper- and hypothyroidism.

So how does this relate back to the MIND Institute and autism research?

Levels of PBDEs and related metabolites in cases of autism have been examined by our intrepid UC Davis team. This paper from Hertz-Piciotto and colleagues measured serum PBDE levels in children with autism vs. developmental delay vs. asymptomatic controls. They did not report any significant differences among the groups, the groups made up of participants from California, but noted high levels of PBDEs in all. OK, you might say so there was no difference, but wait.. what if there might be some difference in the way that such compounds affect a person, a person with autism perhaps? During preliminary study this is what was hinted at in this paper by Ashwood and colleagues, who suggested an altered sensitivity to a specific PBDE, BDE-47 resulting in an increased inflammatory response in cells from people with autism spectrum conditions compared with controls. This finding follows other research suggestive of a potential association between BDE-47 and attention problems.

As with any environmental agent, it is nearly impossible to ascribe an effect in isolation because people do not live in a vacuum. As a population, we potentially face hundreds if not thousands of other exposures which might be contributory to any effect. Unless you measure them all, there is always doubt. Having said that, I don't want to take away from the findings of the study by Zota and colleagues. Findings which require replication and follow-up of infants born to mothers with such high levels, and if deemed necessary, urgent action to minimise any associated health or developmental risks.

I leave you with a song by a footballer which many North-Easterners will know well. It's probably not going to win a Grammy but harks back to happier times for the gentleman in question.

* Zota AR. Polybrominated diphenyl ethers (PBDEs), hydroxylated PBDEs (OH-PBDEs), and measures of thyroid function in second trimester pregnant women in California. Environmental Science & Technology. August 2011.