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Unravelling the mystery of autism: Interview with Dr. Peter Szatmari

Dr. Peter Szatmari, Director of the Offord Centre for Child Studies, made headlines recently for his role as one of the lead scientists in what has become the largest genome scan ever attempted in autism research.

He and Stephen Scherer of The Hospital for Sick Children are part of an international team that has zeroed in on two previously overlooked areas of the human genome – a gene called Neurexin 1 on Chromosome 2 and a region of Chromosome 11 that houses genes involved in the brain chemical glutamate, an important neurotransmitter.  We interviewed him to learn more about how these may contribute to a child’s chances of having autism, and what this latest discovery means for children and their families.

Q. You’ve been diagnosing children with Autism Spectrum Disorders (ASD) for more than 20 years, and you’ve seen a lot of developments take place that have increased our understanding of this complex disorder.  How significant are these latest findings?

A. Potentially, it’s very significant.  If we want to come up with a biological marker for diagnosis and a biomedical treatment that addresses the fundamental deficits that individuals with autism have, then we have to understand the causal chain that goes from gene to disorder.  What we need now is for other researchers to replicate our work, come up with the same findings, and start to build that causal chain.

Q. More than 1,300 families participated in this study.  How important was it to have a sample of this magnitude?

A. It’s true ours is the largest genome scan ever attempted in autism research, and one of the largest for any human disease.  With such a large sample, it’s less likely that we would have come up with these findings by chance alone.  So we can have a lot more confidence in our findings. 

It also allowed us to identify more specific pathways for sub-types of the disorder – affected females, for instance, or those with just language problems.  When you have a really large pie, you can divide it up and still get large samples.  This allows us to gain a better understanding of how individuals come to be affected through different pathways, so that we can ultimately do a better job of diagnosing ASD and treating individuals based on these differences.

Q. In announcing your findings, you said: “Not only have we found which haystack the needle is in, we now know where in the haystack that needle is located.”  What did you mean by this?

A. Every person has 23 chromosomal pairs containing a total of roughly 30,000-40,000 genes.  We know that there are upwards of 10 to 15 genes involved in autism.  Where are we going to look?  These findings not only tell us which chromosomes (or haystacks, if you will) are involved, but where on the chromosome (or in the haystack) the genes might be.  If our hypothesis about glutamate turns out to be true, it’s the closest we have come to date to understanding the biochemical pathway that leads to autism.

Q. Scientists have long suspected that individuals with autism have brains that are “wired” differently.  How does the implication of Neurexin 1 fit with that knowledge?

A. We have known that there are many different ways that the brains of autistic individuals might be affected, but we haven’t known which neurotransmitters might be involved.  This gives us information that is much more specific than we have had to date.  It identifies a specific neurotransmitter system, the same one that has also been implicated in epilepsy.  There are medications already available that affect this specific neurotransmitter system and that are being used now to treat epilepsy.  By zeroing in on  this neurotransmitter system, it brings us that much closer to a diagnostic test and biomedical treatments that can be used effectively on autism. 

Q. You were quoted in the media as saying, “I don’t think it’s inconceivable that we’re going to be able to prevent autism down the road.”  What did you mean by this?

A. If this leads us to better biomedical markers, we will be able to make a diagnosis of autism earlier.  With earlier diagnosis, it’s conceivable that we could put in place interventions prior to full development of the disorder, which is somewhere between 18 and 24 months of age.  We may even be able to intervene before the end of the first year of life, and to me that sounds like prevention.

Q. How close are we to having a DNA test that would diagnose autism in babies or even before a baby is born?  How will this knowledge change the quality of life for these children and families?

A. The first step, as I said before, is to have someone replicate our finding and agree with it.  The second step is to know how many cases of autism this finding accounts for.  Then we need to see if developing a diagnostic test is effective and cost-efficient.  It should happen within the next 10 years for sure.

It will have a big impact on the quality of life for these children.  We won’t have to rely so heavily on behavioral information, which is the biggest stumbling block now to getting an early diagnosis.  And with an early diagnosis, we can intervene earlier to change the life course of the disorder and to reduce the severity of the symptoms so that these children can live more typical lives.

Q. How do you answer the criticism from some people that, far from a “breakthrough” that brings us closer to knowing the cause of autism, these latest findings merely prove how big a mystery autism is?  Just how big is the challenge ahead of you?

A. There is some truth to what they say.  We’re getting closer but we’re also getting farther away because it opens up more questions that we didn’t have before.  But at least they’re the right questions and that’s a step forward.  As far as the challenge that lies ahead, it’s a big challenge, but ever so slightly less challenging than it was the day before yesterday.