One of areas of genetic interest of autism is a region of chromosome 15. Only about 3% of people with autism have the mutation, but 80% of those with the mutation have autism. It is so important that people with duplications of this area have formed their own advocacy group called the Dup15 Alliance. I was honored to attend their family an scientific meeting and give a summary of what scientists have learned about autism through studying this chromosome, how kids with this mutation and autism are similar and different from those with autism but not the mutation, how the families are managing life threatening seizures, what the gene does, what the brains look like, and how mutations of this chromosome do in fact interact with the environment. Thank you to the scientists who study this area and the very brave, selfless and amazing parents who I talked to.
In order to ensure that researchers have enough brain tissue to understand autism spectrum disorders, the education and outreach campaign is being expanded past families to doctors and professionals that have access to tissue. One of these groups is neuropathologists. At their annual meeting this past week in Los Angeles, and entire afternoon was spent dedicated to autism and the features of autism in the brain. A summary of the presentations is included in this podcast. Speakers emphasized that the way the brain works in childhood is not the same way it works in adulthood, and a study out of UCSD showed that the genes that are affected in children with autism are different than those in adults with autism. The mechanisms of genes controlling the developing brain vs. those which affect ongoing maintenance are different. This calls to make sure scientists understand all ages of people with autism, because as the brain changes, so do the needs of people with ASD.
This week, autism lost a pioneer and advocate for autism research: Isabelle Rapin, MD, a neurologist from New York’s Albert Einstein University. The first part of the podcast is a brief summary of her accomplishments. The second part is an study called “how to keep your child out of the hospital”, presenting a recent study which looked at risk factors for being an inpatient, rather than an outpatient. These risk factors may not be able to be prevented, but hopefully through identification of what they are, situations might be managed to help those with autism and their families during a crisis situation.
The brain is developing even after birth. So interventions that are given very early have the best chance of remolding and rewiring a brain with autism to prevent autism related disabilities. This week, a group from the University of London, Duke University and University of Washington measured brain activity during tasks that required social attention following 2 months of very very very early intervention. They found that the way the brain responded to social stimuli was more like those without an autism diagnosis. This study shows a biological marker of brain function is altered after behavioral interventions that are intended to do just that – change the way the brain functions.
This week the Infant Brain Imaging Study, or IBIS, published it’s 2nd study on the emergence of changes in the brains of individuals with autism. While red flags for autism can be seen early, a diagnosis of autism is not typically made until after 24 months of age. Using a baby sibling research design, scientists showed increases in the size of certain areas of the brain between 6-12 months. This opens up opportunities for even earlier diagnosis of ASD in the future. Also, a group at Stanford shows the emergence and disappearance of co-morbid symptoms in autism, such as epilepsy, schizophrenia and ADHD, which are dependent on sex and age. Together, these studies show that autism begins very very early and symptoms and behavioral and biological features change over time.
With hundreds of genes, thousands of environmental factors, and now sex being variables in determining risk for autism, where should science start? Over the decades researchers have been able to start narrowing down the combinations based on specific behaviors of interest, genes, and mechanisms which may narrow down which gene, which environmental factor and which sex. Dr. Sara Schaafsma and Dr. Donald Pfaff from Rockefeller University combined the three, and found that epigenetic changes in an autism risk gene called contact in associated protein like 2 contributed to elevation of risk for autism behaviors following maternal infection. In other words, being male and having the mutation produced small changes, increased by the environmental factor. In another separate study, Dr. Keith Dunaway and Dr. Janine LaSalle at UC Davis used brain tissue to look at a rare variant for autism on chromosome 15. Typically, mutations of this area of the genome are thought to cause autism. However, the effects of these mutations are also increased when environmental factors are present, leading to more de novo mutations. These are all examples of scientific breakthroughs that are helping better understand what causes autism. Even when it looks like one thing, it’s multiple things.
A gene that controls electrical activity in the brain, SCN2A, has been linked to autism for awhile. But recently, a new study from China shows that mutations of this gene are seen in about 1% of people with autism. This may put it into the category of the rare mutations that have a major contribution to autism symptoms. In addition to autism, mutations of these gene are associated with seizures and epilepsy. Because of the relatively high rates of mutations of this gene in autism and epilepsy, an amazing group of motivated families formed an organization to help support and awareness for this gene mutation. This week’s podcast includes a message from one of the leaders of this foundation: FamileSCN2A who are dedicated to help their children with the knowledge about their child’s genetic makeup.
Biomarkers can help distinguish different types of features but this week they were used to predict who would respond to Pivotal Response Training, or PRT. Researchers, led by Pam Ventral at Yale looked at how the brain responded to a social or non social situation as well as baseline features on standardized measures. Remarkably, these brain signatures were better at standard behavioral assessments at determining who would respond most positively to PRT. This study has enormous implications for personalized medicine approach and demonstrates how early studies in biomarkers many years ago have paid off for those with autism.
On October 14th, the Autism BrainNet hosted it’s first webinar around how brain tissue findings affect people with autism. First, Shafali Jeste, MD, from UCLA explained what seizures were, how prevalent they were in people with autism, and what the risk factors for them were in ASD. Next, David Menassa from Oxford University described recent findings in brain tissue which showed how glia cells, or the cells of the brain that support neurons, are affected in ASD and how epilepsy affects these changes. The introduction of the webinar is missing but only for a few seconds. Thank you to Drs. Jeste and Menassa for participating in such a great informational event and for everyone that registered.
This week’s podcast is inspired by a new study in PNAS thatlooked at the role of methylation of the oxytocin receptor in social behavior in people without autism. Together with studies of the brains of people with autism, it suggests that filling the brains with oxytocin may not be the best approach for treating social impairments. Instead, compounds that turn on or turn off the genes that control oxytocin may be more appropriate, and it also may help explain variability in why some people respond to oxytocin treatment, and why others do not. Also, scientific technology has a new way of studying the influence of the environment on brain development.