With Autism, one Size Doesn't Fit All

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With Autism, One Size Doesn’t Fit AllBy AMY LENNARD GOEHNERRECOMMENDTWITTERLINKEDINSIGN IN TO E-MAILPRINTREPRINTSSHARE G. Amaral is the director of research at the M.I.N.D. institute at the University of California, , and the principal investigator of the Autism Phenome Project, an early-phase research study comparing children ages 2 to 3 1/2 who have autism with their peers. The goal is to distinguish different types of autism based on extensive medical exams, gene and blood tests, immune measures,M.R.I. brain scans and other biomedical and behavioral markers. The researchers have recruited just over 300 families for the study and are recruiting additional volunteers.Enlarge This

Image Amaral, Ph.D.OverviewsAutismAutistic BehaviorReporter's FileQuestions for Your DoctorClinical Trials5 Things to KnowMultimediaInteractive FeaturePatient Voices: AutismQ. Where are you in the Autism Phenome Project study?A. One of the major stumbling blocks of understanding autism is that it’s incredibly heterogeneous. Some kids with autism have severe developmental delays, but others have normal or even enhanced I.Q.’s; some have epilepsy,mental retardation or gastrointestinal problems. You are looking at kids who have very different biological and comorbid features, but all are under the umbrella of autism spectrum disorders. The goal of this project is to identify subtypes of autism. Once we identify those, we believe that we can go after the cause for each one in a more productive fashion.It is almost certain that autism has multiple causes, and it might be better to study each one independently. We have now tried to do enough behavioral and biological analysis of the kids to see if there are clusters of factors that will allow us to subtype autism.Now that we have 300 subjects, it turns out the answer is yes. Some of these types may be defined genetically, others by the pattern of brain development and still others by the presence of immune abnormalities.We’ve just started publishing some papers on the development of the brain of kids with autism. Certain

brain regions, such as the frontal lobe and amygdala, seem to have abnormal growth patterns. The amygdala, for example, which controls emotion — particularly negative emotion — undergoes an accelerated growth in about 40 percent of the boys with autism in our study.Q. What does an enlarged amygdala tell you?A. Brain growth is like a symphony, and all parts must be developing at the correct tempo. If one grows too fast, we believe that it may develop abnormal connections and ultimately function improperly. The real question is: Why does the amygdala grow out of sync with the rest of the brain?Q. If the amygdala of a child with autism is enlarged, would that then correlate with a particular subtype of autism?A. Right. It’s the beginning of being able to develop a subtype. What other features might correlate with the abnormal amygdala growth? We’d like to know what causes this rapid growth so that it might give us some targets for treatment that would be different from treatment of kids whose amygdala is normally growing.For example, many people with autism

have anxiety disorder. And the amygdala is a danger detector and involved in the generation of fear. We typically don’t see a lot of anxiety in kids this young. But as they get older, we’ll be able to determine whether they are showing greater signs of anxiety. So several features would come together that would constitute one type.Q. How many subtypes of autism do you anticipate you will identify?A. It’s too early to tell. There are indications that there may be types defined by abnormal brain growth or abnormal immune dysfunction.Another thing that’s happened is that the field has gotten a clearer understanding of thegenetics of autism. I think that it is safe to conclude that there is no single autism gene. We already know of about 20 genes that are risk factors. If there’s a mutation of one of these genes or a loss of the gene or even duplication,

it can increase the risk for a person having autism. But if you have any one of those mutations, it doesn’t automatically mean you are going to have autism. And of those 20 genes, there’s not a single one of them that’s associated with more than a few percent of all cases of autism. The punch line is, in autism, one size doesn’t fit all.Q. Is there a test to see if a parent is carrying a gene that causes autism?A. No. The genetics are complicated. Some of the risk factors are hereditary or inherited from a parent. But we’ve also learned that some of the genetic mutations probably occur at conception, where

you lose or duplicate DNA.Q. There’s always talk of environmental triggers for autism. Is that related to the children’s propensity because of their genetic makeup?A. That’s the most likely guess. You can have genes related to the immune system. And if your immune system is taxed and doesn’t work properly, that could lead to a result where you could alter brain development and go on to have autism. But we really don’t know which genes and which environmental stresses would be coming together.But there’s evidence now that certain environmental factors contribute bits of risk. Some are surprising. Investigators here demonstrated that families who use flea and tick powder on their pets slightly increase the risk.Q. Is it the case that the more you discover, the more testing you have to do?A. What’s encouraging to me is that it’s not chaotic in terms of the data we’re finding. What is also helpful is once you identify one of these patterns, you can go on to do additional studies to understand the mechanisms leading to the disorder. This translates directly to targets for

treatment.Another example relates to the other part of the brain that grows too fast. It is the frontal lobe, located just behind your forehead. This cortical area is involved in social behavior, planning for the future, theory of mind, self-awareness. We’ve found that some of the kids have an abnormally enlarged frontal lobe. We are starting to see in this case that there are some behavioral correlations. For example, whether you have an enlarged frontal lobe or not seems to be associated with whether you had an early-onset versus a regressive form of autism.Q. What’s the next step?A. I’m convinced that longitudinal studies are essential to understanding autism. We’ve proven the feasibility of carrying out comprehensive biomedical studies of very young children with autism. We have started pilot studies with even younger children — starting at 6 months of age. These are siblings of children with autism who have a higher risk of also having autism. By studying the development of children over time, we are beginning to identify the most salient changes in their biology. We are seeing facets of autism that we would simply not see if only studying adults. The most striking feature discovered thus far is that the trajectory of brain development is dramatically altered in some children with autism.Q. Was that a new discovery?A. Several laboratories have identified abnormal brain growth in autism. This is really a developmental disorder. Something that is happening early on can have an impact on the rest of the development of the child and lead to a lifelong disability.Q. Parents of children with autism have vastly different descriptions of them. Is that consistent with what you are learning?A. This is a real reflection of how heterogeneous this disorder is. But if the biology of every kid with autism were unique, we’d never get answers in our research. I do think as we carry out these longitudinal studies, we’re not going to end up with thousands of autism types. I’d guess it will be in the tens, and maybe even fewer. And once we have the different types, what will be illuminating will be, ‘What’s the overlap between the different groups?’ There are behavioral similarities, and there may be biological similarities. Just as many tributaries feed into one main river, it may be that different genetic and neurological problems feed into one final common pathway that produces the behavioral characteristics of autism.Q. You sound optimistic about someday

finding a cure. Are you?A. Over the last 10 years I’ve seen the amount of resources dedicated to research increase tremendously. The first stage to solving autism is to bring some clarity to what autism is. I think we’ve made really huge strides over the last decade. The Autism Phenome Project is a reflection of the intensity of effort in the field.We also need to be very careful in using the word “cure.†I much prefer to think about decreasing disability and increasing the quality of life for individuals with autism. There are individuals on the autism spectrum that have very special talents and abilities. Would we

want to “cure†these? Obviously not. I am optimistic that we are getting closer to an understanding of the biologies of autism and that this understanding will give us much clearer targets for prevention and treatment of the most serious forms of the disorder.Publish date: 4/13/2011