Top 10 environmental pollutants and autism

I did promise in a recent post on rich/poor kids, older mums/dads and autism, that I would pass comment on the editorial by Landrigan and colleagues* (full-text) published in the journal Environmental Health Perspectives. I couldn't let this paper go by without some reference given that it provides quite a bit of background as to where autism research should be looking if we are to assume that certain aspects of the environment might play a role in symptom onset in at least some cases of autism and perhaps other related conditions.

Indeed there are several other papers in the same journal which might also be relevant to this post, including:

• This one by Sheldon and colleagues** (open-access) looking at pesticide exposure and autism,
• This paper by Kalkbrenner and colleagues*** (open-access) looking at maternal smoking during pregnancy,
• This paper by Wayman and colleagues**** (open-access) looking at non-dioxin like polychlorinated biphenyls (PCBs) and dendritic growth,
• and another paper by Wayman and colleagues***** (open-access) on ryanodine receptor dysregulation following PCB exposure.

I have to say that I don't have the time, energy or expertise to go through each and every one of these papers but would instead refer to quite a nice summary here on two of the papers and invite any comments from those that did read them. Please also consider this entry as a sort of continuation of my interest in pesticide exposure and health as per this and this post.

There are a few things to note about the Landrigan commentary including:

• Acceptance that autism is a family of conditions of which the authors suggest that about 30-40% of cases might be attributable to genetic inheritance.
• An estimated 3% of all neurobehavioural conditions are "caused directly by toxic environmental exposures" and some 25% caused by interactions between environmental factors and inherited susceptibilities.
• There is accumulating 'proof of principle' evidence for some role for environmental factors in cases of autism. 
• Added to what is already known about the neurological and developmental effects of some of these environmental agents combined with the growth and growth in areas such as epigenetics, there are some pieces of the research puzzle which seem to overlap with evidence from autism research.
• A workshop titled 'Exploring the Environmental Causes of Autism and Learning Disabilities' generated a list of 10 chemicals widely persistent in the environment which might cause developmental neurotoxicity. These were: Lead, Methylmercury, Polychlorinated biphenyls (PCBs), Organophosphate (OP) pesticides, Organochlorine (OC) pesticides, Endocrine disruptors, Automotive exhaust, Polycyclic aromatic hydrocarbons (PAHs), Brominated flame retardants, Perfluorinated compounds. The chemicals with links will take you to previous posts on this blog which have covered the compound in question; some with autism in mind, others with a more peripheral connection.

I'm sure you will agree that there are quite a few very bold statements included in this editorial not least the top 10 chemical targets for further research. I imagine that there will be some discussions on the rights and wrongs of naming and shaming the potential chemical offenders as time goes on.

The good news about these chemicals / compounds is that with the technology available these days, all are perfectly testable, and can be analysed in various biological fluids. One would therefore imagine that designing a large enough study covering people with autism, their parents, even siblings and appropriate comparators, controlling for comorbidity, even incorporating some degree of 'endophenotype' research and genetic / epigenetic elements is a perfectly feasible way of testing one or more of the '10 chemical hypotheses'.

Assuming some connection is confirmed and bearing in mind the complexity of cause-and-effect, the next question might be 'what can we do about it'? Minimising contact with these agents, particularly during conception and pregnancy and into early childhood, utilising the various ways and means available to remove these chemicals from the body - yes, even using that dreaded biomedical 'mumbo-jumbo' word detox - and assessing outcome both behavioural and biochemical (see here). Who knows perhaps even looking at the various detoxification mechanisms such as glutathione and its relations which have ascended up the evidence ranks quite recently to note any possible association.

Stop already with the speculation, I hear you cry. And I will.

To finish, do you feel compelled to walk like an Egyptian?

* Landrigan P. et al. A research strategy to discover the environmental causes of autism and neurodevelopmental disabilities. Environmental Health Perspectives. April 2012
DOI: 10.1289/ehp.1104285

** Sheldon JF. et al. Tipping the balance of autism risk: potential mechanisms linking pesticides and autism. Environmental Health Perspectives. April 2012
DOI: 10.1289/ehp.1104553

*** Kalkbrenner AE. et al. Maternal smoking during pregnancy and the prevalence of autism spectrum disorders using data from the Autism and Developmental Disabilities Monitoring Network. Environmental Health Perspectives. April 2012
DOI: 10.1289/ehp.1104556

**** Wayman GA. et al. PCB 95 promotes dendritic growth via ryanodine receptor-dependent mechanisms. Environmental Health Perspectives. April 2012
DOI: 10.1289/ehp.1104832

***** Wayman GA. et al. PCB 95 modulates calcium-dependent signaling pathway responsible for activity-dependent dendritic growth. Environmental Health Perspectives. April 2012
DOI: 10.1289/ehp.1104833

Household chemicals and immunity

Mucky paw prints @ Paul Whiteley

Looking around most homes, it is easy to spot the modern face of physics and chemistry in action. I'm not specifically talking about microwave ovens or those other technological labour-saving gadgets like that fancy espresso coffee-maker that we seem so hooked on; but rather more humble examples like the non-stick frying pan or the variety of grease and stain resistant compounds we use to save hours and hours of cleaning and scrubbing.

Whilst it is perhaps slightly unfair to demonise all the chemicals we use - as per this article on the misrepresentation of the words 'chemical-free' - there is a growing recognition that collectively, we have not paid as much attention to the potential effects of some of these everyday substances as we should have done. I'm thinking back to older posts on things like polybrominated diphenyl ethers (PBDEs) for example.

Another case in point is this recent article by Grandjean and colleagues* linking exposure to perfluorinated compounds (PFCs) with a reduction in humoral immune response and in particular, the production of antibodies to two routine childhood vaccines. Quite a good summary of PFCs is here.

There has been some pretty widespread coverage of this paper in both the science and lay media. A summary of the research:

• Based in the Faroe Islands, 587 children born between 1999 and 2001 were included for study.
• Levels of several PFCs including perfluorooctanesulfonic acid (PFOS) and perfluorooctanoic acid (PFOA), were analysed from maternal blood samples taken during pregnancy alongside children' blood samples drawn at ages 5 and 7 years reflective of pre- and post-natal exposures. PFC values were subsequently compared against children's antibody responses following tetanus and diphtheria immunisation.
• There was a relationship between levels of PFCs and the concentration of antibodies detected in that pretty uniformly PFCs were negatively correlated with antibody levels. That is a higher concentration of PFCs were associated with lower antibody response. Indeed under certain conditions, PFC levels placed children at risk of not having clinically protective levels of antibodies to these diseases. 

The potential implications of this work are pretty far-reaching although there are perhaps a few things to note. This is not the first time that PFCs have been linked to immune effects. Cord blood IgE levels correlated with PFC according to this study and those dastardly proinflammatory cytokines were connected according to this research. This and other similar research points towards immunomodulatary effects from PFCs outside of their other possible links to things like cholesterol and reproductive ability.

In terms of source, PFCs have been detected in several dietary sources particularly seafoods including fish and shellfish. Given the placement of the Faroe Islands (i.e. islands in the North Atlantic), it is not surprising that seafood is high on the menu including some more traditional dishes such as dried fish. Exposure-wise therefore, whilst the focus of the current study is on more everyday objects as being a source for PFCs, intake through food should also be kept in mind.

As with every study, replication is required. Replication not just in children (and mums) from the Faroe Islands but also from other parts of the world. A little more understanding about the relative contribution of genetics and other environmental factors influencing susceptibility might also be useful given that we all seem to be carrying at least some quantity of these compounds around with us. If the results are replicated, it is then up to the various companies and regulatory bodies to make some important decisions on the basis of perceived cost and benefit. As with many chemicals in regular use, it is not just a case of stopping production tomorrow and everything immediately changes overnight. The persistence of these compounds is such that any changes now won't really be seen for several years; the US EPA for example, estimating the serum half-life of PFOS in humans at 5.4 years.

I try not to be alarmist on this blog because ultimately these are studies which whilst providing data on association, cannot possibly take into account the wide variety of other factors potentially involved any relationship. Having said that, the evidence against PFCs is starting to accumulate from both animal and human studies. Perhaps the next time I want to fry my bacon rashers - yes, some people still do that - in healthy olive oil of course, I might just reach old skool for the non non-stick pan.

To finish, how about a little punk rock about that most sensible of floor surfaces, linoleum?

* Grandjean P. et al. Serum vaccine antibody concentrations in children exposed to perfluorinated compounds. JAMA. January 2011. DOI: 10.1001/jama.2011.2034