Thursday 26 May 2011

Pesticides and autism: chapter I

As we are constantly being told, autism is one of many conditions whose aetiology is thought to be governed by a variable, yet symbiotic relationship between genes and environment. I personally find this explanation to be quite a satisfying one because lots of conditions, Phenylketonuria (PKU) and coeliac disease for example, offer similar templates to work from despite being (supposedly) separate and independent of autism. My last post on pre- and peri-natal vitamin use combined with the presentation of SNPs in particular genes as indicators of 'risk' of autism is also a good example of such a gene-environment relationship.

A few questions do however remain: what is the relative percentage contribution of genes and environment? If it is variable, both inter- and intra-conditions, why? and what are the precise genes and environmental stressors in relation to something like autism for example outside of co-morbidity? I would perhaps like to tackle some of the evidence covering these questions (anyone have an eternity?) over the course of my blog-a-thon, but for today, I want to discuss the potential role of one particular environmental stressor: pesticides.

'Travelling through hyperspace ain't like dusting crops boy'. Wise words from Mr Han Solo in Star Wars IV: A New Hope. Actually dusting crops is a classic example of pesticides in use (I suppose they have pests even on Tatooine). Despite all the good intentions for using them, pesticides have however developed a bit of a bad name in some quarters, perhaps with some good reason. This, despite the fact that they actually do quite a good job at doing their job, i.e. getting rid of pests.

Perhaps the core problem is that some of the same biological processes that certain pesticides are designed to target in order to kill insects/rodents/plants are processes that we humans tend to use quite a lot as well. Humans are after all, not that dissimilar in basic biology from our flatmates who we share this lovely rock with. Who knows if the tables were reversed, we would probably be extinguished by our insect masters using the same cocktail of pesticides.

Seriously though, when it comes to a possible connection between pesticides and autism, the research is equivocal, at least at the moment. There is quite a lot of opinion linking the rise in autism prevalence at least partially with things like pesticide use. There is, for example, some suggestion of susceptibility genes being geographically distributed in autism, with particular reference to the paraoxonase (PON) gene and its variants. Levels of paraoxonase (PON1), an enzyme involved in clearing certain pesticides, has for example, been examined in conjunction with certain pesticides and infant neurodevelopment. All this and data from environmental tracking programmes suggesting a possible association between autism and pesticide use makes for a feasible relationship at least in some cases.

The issues, however, with the research so far are these:
  • Pesticides cover a range of different products - the chances are that you will have had some in your medicine cabinet at home at one point or another.
  • Because of their extensive use over the years, pesticide residues are endemic to our environment (some taking years to break down) hence we are all pretty much involved in this chemical soup in our day-to-day lives.
  • The fact that so many pesticides have been, and continue to be, used means that we don't have a lot of data on their potential combined, synergistic effects.
  • Establishing a 'cause and effect' relationship outside of other factors potentially involved is problematic. Unless you have a direct exposure event, like during sheep dipping for example, it is easy to pose the question: what about the contribution of other (environmental) factors?

That is not to say there may not be a relationship between onset of developmental conditions, pesticide exposure and genes - indeed, the evidence does appear to be swaying towards such a notion. But as always, things are rarely so simple and straight-forward. Take for example one quite important, but perhaps peripheral area of inquiry, on the possible usefulness of compounds such as galantmine in autism.

Galantamine is an interesting compound normally used in the treatment of Alzheimer's disease. One of the proposed modes of action of galantamine is its inhibitory action on acetylcholinesterase activity; whereby it increases the amount of acetylcholine available. This is pretty much the same action that certain types of pesticides (particularly the organophosphate variety) are known to do with the exception that galantamine tends to be reversible in its inhibition and some of the OPs not so. Query: pesticides and galantamine might work on the same type of enzyme - why then is galantamine suggested to be a possible intervention option for autism (and not only just in one trial)?

This is where it starts to get confusing as I am fast reaching the limits of my knowledge on this topic. Granted that there are many, many different classes of pesticides with various different modes of action and I am sure that the pharmacologists and toxicologists out there would be able to provide an explanation based on dosage and that reversible/irreversible mode of action. It could also well be that galantamine has other effects on autism outside of acetylcholinesterase which produce the positive effects reported and likewise pesticides might be acting on other biological systems potentially pertinent to conditions like autism. Let us also not forget that autism is more likely autisms and hence not readily carrying universal connections from case to case even despite the recent neurological findings. I think I need to do a little more reading on this topic, so perhaps be prepared for a chapter II and a few more chapters to this post.

Cue the Star Wars opening crawl.

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