On the ’cause’ of autism

Posted by: passionlessdrone on: April 22, 2009

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There used to be a small time hockey league that had a team in my town, the Tigersharks. This was long ago, many years before I met the mother of Kid Autism, and indeed, during a time in my life in which it would not be unusual to go out on a Tuesday night, take some alcohol, watch a hockey game, and then take some more alcohol.

As anyone who has ever attended a hockey game is aware, the intermissions are painfully repetitive; especially if you have season tickets. There is a very finite, and low, number of times you can listen to the chicken dance without wanting to randomly punch people who are participating; the more fun they’re having, the more punches they deserve.

In any case, on this one particular evening, during one of the intermissions, there was a five minute, little league ‘hockey game’. None of the participants looked to be more than six years old, and I’d bet a few were four. To describe what transpired as a game is generous; it was more like two goalies, and a mass of ten kids swarmed around the puck like a pod of baitfish. All of the kids were smacking at the puck with their sticks, skates, and simultaneously pulling and pushing each other. The blob of children moved up and down the ice randomly; you could see each child trying to get the puck, but trying to tell which child was actually having an impact at any given time was impossible, there was just too much going on and too many combined small forces being applied.

At one point, the puck squirted free and a single child embarked on a slow motion breakaway that took a full minute. The goalie fell down, and the little guy fanned over the puck in front of an open net. It was, far and away, the most exciting breakaway in the history of hockey.

In many ways, when we look at what have been identified as risk factors for an autism diagnosis, it bears no small resemblance to a pee wee hockey game. There are lots of little things happening, and figuring out which is a cause, which is a result, and which is the result of a result of a result is very difficult. And lots of these forces are probably be different for any individual child.

In very rare instances, we have well established risks that greatly increase (or dictate) autistic behaviors; the Fragile X polymorphism for example. But what is found with far greater frequency is a genetic polymorphism or environmental exposure that raises the risk of autism, just a little bit; the equivalent of one pee wee out of ten taking a whack at the puck.

For example, a recent paper regarding genetic alleles involving the MET pathway suggests that having alleles in related genes even further increases the risk of developing autism, but not by much.

From the abstract:

Replicating our initial findings, family-based association test (FBAT) analyses demonstrated that the MET promoter variant rs1858830 C allele was associated with ASD in 101 new families (P=0.033). Two other genes in the MET signaling pathway also may confer risk. A haplotype of the SERPINE1 gene exhibited significant association. In addition, the PLAUR promoter variant rs344781 T allele was associated with ASD by both FBAT (P=0.006) and case-control analyses (P=0.007). The PLAUR promoter rs344781 relative risk was 1.93 (95% confidence interval [CI]: 1.12-3.31) for genotype TT and 2.42 (95% CI: 1.38-4.25) for genotype CT compared to genotype CC. Gene-gene interaction analyses suggested a significant interaction between MET and PLAUR.

What this tells us is that having a particular polymorphism in the PLUAR gene nearly doubles your risk of having autism, and another polymorphism on the same gene increases your risk of a diagnosis by almost 2.5 times. All in all, this is not too large of an risk factor; after all, despite all of our “greater awareness”, autism is still relatively rare; a doubling of risk still leaves you very, very unlikely to have autism.

The currently understood environmental exposures, at this time, all prenatal, have also been shown also to increase your risk of developing autism by very small increments. This paper on maternal exposure to pesticide application suggests that mothers living closest to fields with particular types of pesticides increases the risk of having a child with autism by about six times compared to women bearing children the furthest from those same aggricultural fields.

Other genetic analysis have provided evidence that having a combination of mutations can confer much greater risk than having either one of the mutations alone. In other words, having polymoprhism A raises your risk of autism by two, and polymophism B raises your risk by two; but having both polymoprhism A and B raises your risk of diagnosis by seven.

What all of this means regarding finding a cause of autism is that instead, first and foremost, we need to expand our horizons, and instead, accept that there are many possible causes of autism; there could be dozens of combinations of genetics and environmental influeces that eventually result in an autism diagnosis. Once we accept this reality, it makes our task that much more difficult; but accepting a difficult assignment is still far superior to tilting away at an easier goal; one that cannot be reached with any utility.

There are a diminishing number of people who claim that autism is either solely or genetic, but this (long needed) realization needs to go further; instead, we need to acknowledge that autism is the result of many different genetic and environmental actions working in concert.