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Is Autism Caused By Genes or the Environment?

Wilczynski:  Dr. Walsh, dozens of genetic defects have been identified and associated with autism spectrum disorders.  Tell us, from your research, what have you learned about genetic roots of autism?

Walsh:  Well, so far the genetic studies of autism have been leading us to much the same sorts of ideas about its root cause.  You’ve already heard about this idea that there is problems with connections in the brain.  Now the brain is made up of cells that have fibers connecting different parts, sort of like electrical circuits and what is unique about the brain though is that those fibers and those connections change.  The fibers and the cells are the hardware, but then the brain develops different apps or different software apps for language or apps for social behavior. And it seems like it’s these patterns of changes in connections that don’t seem to work and the genetics lead us to genes that regulate these patterns of connectivity, regulate the synapses that connect one brain cell with another brain cell.

Wilczynski:  What have we learned about environmental triggers for autism?

Bookheimer:  So far there is not very much known about environmental triggers for autism.  We know for example recently that the age of the father is related to additional autism risk.  There is a recent study coming out of USC showing that exposure to small particulates, the proximity to major freeways, confers a small additional risk. But I think that those are the only two I can think of that we’re pretty sure are at least associated with autism and probably don’t explain a whole lot of the increased risk of autism. 

Walsh:  One of the things about again the genetics leads to in terms of the mechanisms is that the sorts of genetic abnormalities that we see with autism involve these synapses and the synapses change in response to the environment. In fact, although we think that there is a large genetic component to the disease it’s by no means all genetics in the sense that the genes that are in play are those regulate the way the brain responds to the environment and so that is good news in the sense that we know that there are ways that the brain can be changed by different sorts of teaching, different sorts of environments, enriched environments. But that also implies that that genetic predisposition is not immutable, that there might be ways it can be modified or improved.

Fischbach:  Let me just amplify what Chris and Susan said about coming back to the environment at the end.  What I think of when I think of the genetics of autism is two things.  One, it’s complex. And two, it’s really advancing rapidly, a lot of it due to some of the work Chris has done in families in the Middle East that are now here in this country. But it’s not going to be a simple answer of one gene causes autism.  In fact, what is much more likely is there may be more than 100 genes that enhance the risk of autism.  There is a difference between a risk factor and a cause.  There may be a few diseases we know—more than a few—where one gene causes a disease, like sickle cell anemia in Africa and more close to home, Huntington’s disease, where if you have a mutation in a certain gene you will have that disorder. In autism there is just genes in part more or less of a probability that you will have the disorder, and that is where interactions with the environment are key.  Genes are not in this case, certainly not fate.  You have to understand how the genes influence environment. And I think what Chris was saying was one of the important things in environment is how you learn things and that has to do with the connections between nerve cells in the brain and there are over a trillion of them. And some change right now as we’re talking to each other and some don’t change.  Some are pretty... more or less fixed, but some do change. And it’s turning out that many of these genes are pointing to the biochemistry that affects these connections in the brain.  That is the hope. That these genes will all converge somehow and point to one or a few targets in the brain. But it won’t be one gene.

But there are many, many ways to affect synapses, the connections, especially to affect the way synapses change with experience, so that is the hope, but first one of the primary goals is to get the cast of characters.  How many genes are we talking about?  Who are they and what are they pointing at?  And that is when the really interesting, I think, work will begin and we’re getting close to that.


Is Autism Caused By Genes o...

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