An interview with Raphe Bernier, PhD…

We haven’t heard much lately on The Autism Blog from our beloved clinical director, Dr. Raphael Bernier. I caught up with him today (if you know Dr. Bernier, you know that requires a good pair of running shoes and a good sprint) to find out what’s new in the world of autism research. Here’s what he had to tell us:

Lynn: Parents wake up every day hoping there is promising news about autism research. Is there anything new to report today?

Dr. Bernier: Yes, there is! As I was preparing my BBQ fixings for the big day tomorrow, I was reflecting on one of our studies that published today.

Our study reported that a new subtype of autism has been identified using a genetics first approach.

Lynn: Parents have heard about this attempt to define subgroups of children with autism. Tell us more about the genetics first approach.

Dr. Bernier: This is exciting – exciting in a way not unlike fireworks are exciting – kind of like scientific fireworks. But, I’m getting ahead of myself. The genetics first approach . . . what’s that? Well, for years folks have been saying: “If you’ve met one individual with autism, you’ve met one individual with autism.” Every individual with autism is so unique. Scientists use terms like heterogeneity to describe that individual uniqueness within one diagnostic category.

In the 80s and 90s scientists and clinicians tried to develop subgroups within the diagnostic category of autism in the hopes of better understanding the causes of autism. They also hoped to find insight into the prognosis for individuals within the spectrum, and most importantly, to provide interventions that were effective for a given individual.

But, in the 30 years of research it became clear that the behaviorally-defined subtypes didn’t match on to what we’re learning about the causes of autism, didn’t provide insight into course of autism symptoms for a given individual, and didn’t match onto targeted treatments.

Lynn: So researchers decided then to turn the attention away from looking at subtypes based on behavior and focused on subtypes based on genetics?

Dr. Bernier: Yes. Given the major advances in genetics in the past decade, we’ve been able to identify specific genetic events that are likely playing a role in autism. The genetics first approach capitalizes on these advances and involves careful follow-up and understanding of individuals with autism who have specific genetic events.

Lynn: Scientific articles are quite technical. Can you tell us in layman’s terms, about the study and its findings?

Dr. Bernier: Sure, so it starts three years back when scientists at the University of Washington moved the field of autism forward several years with a few pioneering studies. Through the support of the families participating in the Simons Simplex Collection, geneticists combed through the DNA for all the children with autism in this national study and identified specific gene-disrupting events that impacted a couple of different things in the cells of our body:

  • These disrupted genes played a role in the way that brain cells connect and communicate and
  • These disrupted genes acted as part of interactive network of genes involved in how other genes turn on and off.

And among these genes, one particular gene stood out: CHD8.

It stood out because of all the identified disruptive genes, it was the one most commonly disrupted.

Lynn: How common was it?

Dr. Bernier: By common, I mean that this same gene was disrupted in 9 children of over 2,000 with autism. How can that be common? Well, it speaks to how rare each of these particular genes is. CHD8 was identified far more often than the other 800+ genes identified to be playing a likely causal role in autism. I’m getting distracted again. All the thoughts of burgers and hot dogs are pulling me away from genetics.

Lynn: Back to the paper, please Dr. Bernier.

Dr. Bernier: Yes. We decided to work with individuals identified with CHD8 disruptions to see if any particular patterns emerged. And many indeed did.

  • Firstly, regardless of how the individuals were found, most, if not all had autism. This is new for most genetic events linked to autism. For example disruptions to chromosomal region 16p11.2, while accounting for about 1% of all cases of autism, are associated with a variety of other disorders and not just autism. CHD8 on the other hand, at least so far, seems to be very strongly linked specifically to autism.
  • Secondly, most of the individuals with CHD8 have strikingly similar physical features: most have macrocephaly, meaning a very large head circumference, prominent forehead, and eyes that are wide set and that have a gentle downward slope on the outer eye.
  • Thirdly, most of the individuals with CHD8 also have significant gastrointestinal disturbances, primarily constipation. A clear pattern of symptoms emerged for these kids.

What our collaborators then did was to see if these patterns emerged in an animal with this same type of disruption to CHD8. And, sure enough, zebra fish with CHD8 disruptions also had a large head size, and GI problems. It’s fascinating; what our colleagues did was feed fluorescent pellets to the zebra fish and track how long it took for these pellets to pass through the GI system and time and time again, these poor zebra fish were constipated.

Importantly, the underlying mechanism can be explored in animals and what the scientists found was that CHD8 was leading to disruptions in the growth and migration not only of brain cells, but also cells from the enteric nervous system, the cells that help move food along the GI system. 

Lynn: Wow. This is an important discovery. I have so many follow-up questions. First, what would you say the percentage is of individuals on the spectrum who fit this subtype?

Dr. Bernier: Right, so the number of kids with this particular CHD8 event is going to be less than half a percent. So, not a ton, but it provides insight into other gene events because many of the genes that are co-expressed with CHD8 have also been linked to autism as well.

Lynn: We just posted a blog about GI disturbance in autism. Research is finally validating what parents have known for years – that in some kids, there is definitely a link between autism and GI troubles. Yes?

Dr. Bernier: For years parents have been telling us that GI problems are a significant factor for their children and it took a long time for providers and the scientific community to respond. This doesn’t mean that GI problems are causing autism, but on the contrary highlights a common genetic mechanism linking autism symptoms and disruptions to GI.

Now we see a specific mechanism underlying both the autism symptoms and the GI symptoms. 

Lynn: Parents have often wondered if treating the GI symptoms remediates the symptoms of autism. Does this study lend any weight to that belief?

Dr. Bernier: It doesn’t necessarily speak to that, but highlights a genetic mechanism underlying autistic symptoms and GI symptoms. More research is needed.

Lynn: This seems to be a breakthrough in autism research but as a parent of a child with autism, I’ve read about supposed breakthroughs before. What is the significance of this study?

Dr. Bernier: I guess all too often I’m reading about this causes autism and that causes autism and about new breakthroughs, but what is different about this breakthrough is that scientists have finally identified a specific subtype of autism.

What’s important about that you might ask? Well, first of all, it’s clinically helpful because clinicians can use this information to help consider other challenges, such as paying attention to GI symptoms.

Also, with this subtype there is a specific mechanism that can be explored to find targeted treatments that are specific to the child.

Finally, and it’s still early to say, but this particular finding can help clarify the pathophysiology of autism. That is, how does one get from a disrupted gene to the complex pattern of behavior we call autism. In order to understand that, we first need a specific gene that leads to autism and we’ve finally got a solid candidate.

Lynn: What follow-up studies do you think will flow from this one?

Dr. Bernier: I think we’re going to see a whole shift away from scientists comparing 20 children with autism to 20 typically developing children on a brain imaging task and saying that they’ve reached a conclusion. We’ve been doing this for years and we’ve been having a hard time replicating results (which is key in science). Instead, we’re going to be focusing on better understanding each kid in relation to genetic background as opposed to behaviorally grouping kids.

Lynn: Is there anything parents can or should do now if they believe their child fits this subtype? Will providers begin to look for and identify kids in this subtype?

Dr. Bernier: I’ve actually already gotten a clinical referral for a family with a CHD8 event. Parents can always speak with their primary provider if they have questions or concerns about CHD8 or other genetic events. There are excellent resources here at Seattle Children’s and a variety of genetic studies going on right now.

Lynn: Is the bottom line here that providers should listen to parents as reporters of their child’s symptoms?

Dr. Bernier: Absolutely!

Thank you, Dr. Bernier, for reporting on this exciting discovery in autism research. We eagerly await hearing more from you!