University Place  Janet Lainhart Psychiatric Comorbidity With Autism Spectrum Disorder   cc [APPLAUSE]  >> I want to thank you very much for coming today. As you can read in the brochure, I have had the opportunity since 1990 to provide care for hundreds, possibly thousands, of children, adolescents, and adults with autism. So, all the parents who are here today, I know the tremendous effort that you had to have to come here this morning. I thank you so much. I also want you to know that my interaction with all of you today is going to impact the direction of the research and the work that I do here at the University of Wisconsin. So, I thank you in advance for that.  We all know that the manifestations of autism spectrum disorders are striking, and they're striking across the life span. But, despite ability and disability, the cause is completely unknown, in my opinion, keeping a lot of the ability locked in by the disability. We all know that autism is the fastest growing developmental disability, and, from a medical point of view, and I think from a parent point of view, it is a crisis that we don't have any biological markers for autism. We do not know any way to prevent the disorder from beginning. 

We don't know how to prevent complications of the disorder in young people who are already significantly affected. There are no specific treatments based on the underlying neurobiology of the disorder because the neuro basis of autism remains unknown. And I came to the Waisman Center because I believe that the Waisman Center is one of the few places in the world that is going to change all of this. We all know that the identification of infants at risk for autism and the identification of very young children who are just developing autism is incredibly important, and providing early intensive intervention is very, very, very important. And there is now strong evidence to support early intervention, but it's also very important, in both young children and in older individuals, to better understand the biology of the disorder so even more specific, more effective, and more feasible interventions can be provided, particularly for children with autism who are already significantly affected, adolescents and adults with the disorder, it's very important that we understand the neuro basis of autism in them. The majority of individuals who already have autism are destined to live with it for the rest of their life, and one-third may worsen over time rather than improve. Okay, thank you. Usually my voice is too-- Can you hear me now? Okay. Usually my voice is way too soft and people can't hear me. There is substantial evidence that autism is a disorder of brain connectivity. 

We and other groups around the world have found that markers of microstructure of the white matter in the brain of autism is a typical but not uniformly diffused throughout the brain. There are also abnormalities of kind of the surface of the brain, the cortex, and the deep parts of the brain, the subcortical gray matter. So, all of the evidence comes together to provide tremendous evidence that the neuro networks, so the multiple areas of the brain that have to work together for us to perform any particular skill and that really have to work together for us to perform complex skills, like socially interacting with people or communicating with them. These neuro networks appear to be involved in autism, specifically the ones that are involved in the core features of the disorder. But what we also know, in addition to neuro networks involved in social functioning, language, and kind of repetitive behaviors, we also know that neuro networks involved in attention, motor activity, motor control, emotional regulation, and emotional control and kind of the ability to have flexible behaviors and adaptive behaviors are also involved. This is work I did quite a few years ago when I was at the University of Utah, and this was in collaboration with scientists at Boston University, Helen Tager-Flusberg and Susan Folstein. What we did is we just simply looked at behaviors in children with autism over time. And the blue line at the top are children with autism. The dotted red line at the bottom are children who have another developmental disability, specific language disorder. So, the line at the bottom are children who have really significant language impairments. 

The blue line shows that in regard to just severe temper tantrums, so severe emotional regulation, look at the difference between the two groups. So, what this shows is that by 13 to 36 months of age, 40% of the children with autism have developed or have problems with severe tantrums and emotional regulation. And for the parents of these young children, you know better than anyone else how difficult this is for the child, for the parents, and for every individual that's trying to help the child. This is atypical sleep. Once again, children with very severe language impairment on the bottom, children with autism at the top. This is atypical eating pattern. Self-injurious behavior. Aggressive behavior. So, and then this chart shows, it compares the children with severe language impairment to children with autism. So, the children with autism are the green boxes. 

It shows that most children with language impairment by itself, they might have none of these atypical impairing behaviors at all or they might have one or two, but look at the children with autism. Three, four, five of these severely impairing atypical behaviors in addition to the core features of autism. So, when children with autism or adolescents or adults present their problems to us, as clinicians and as parents, we are seeing the tip of the iceberg. We are only seeing the behaviors. We are only seeing what we can observe. We are not able to see what is going on in their brain, and all the different things that might be contributing to the problems that manifestations shown at the tip of the iceberg. There are a number of different causes of emotional and behavioral problems in individuals with autism of all ages. As you know, some of the children just have particularly impairing core features of the disorder. Some of the children are more severely effected in language and communicating, and that can be tremendously frustrating for them and very, very difficult, as you know, for parents. Some of them just are severely impaired in their interaction and understanding of the social world, and that can be severely upsetting and impairing and difficult. 

And then there are a whole host of cognitive problems, deficits in complex information processes, mind deficits which is our very natural ability to kind of read the needs, the feelings, and we try to read the thoughts of other people. But many children with autism, and adults, can't do that their whole life. Executive functioning, which has to do with planning and organization, deficits in central coherence, and then specific learning disabilities. These are all on top of the core features of autism, which are limited. The core features are in the top item. So, how do we recognize and diagnose and somehow treat these additional problems in individuals with autism? Well, it's not easy, but it is possible and it's extremely important to do. In order to understand these additional problems, you have to really understand the core features of autism. You have to understand the behavioral manifestations of these other difficulties, and you have to understand what the child or adolescent is like when he or she has been at their best. You have to know how things have changed over time, and most important, information has to be obtained from someone who really, really knows the child or adult well. These new and additional difficulties in children, adolescents, and adults with autism, once again, we're just seeing the behavioral manifestations. 

Those behavioral manifestations can be due to underlying medical problems. They can be due to underlying other brain problems, other involvements in the neuro circuits that either are present from a young age or that emerge over time. They can be due to kind of temperamental, just kind of almost like personality traits or differences in IQ. They can be due to learned behaviors, and they can be due to the life experience of the child with autism. They can be due to all of the above. So, how common are some of these other emotional and behavioral problems in older children with autism? So, you saw the charts showing the younger ones. This is going to show you older ones, individuals with autism five to 17 years of age. In this really young age group, so this was a very, very, very detailed study, so one out of 10 of these children, five to 17 years of age, had a severe mood disorder, what conceptually is the same as major depression. Many of them had anxiety disorders. Above and beyond just the repetitive behaviors that are part of the core features of autism. 

Thirty-seven percent of them met full criteria for obsessive compulsive disorder. A number of them, a third, met criteria for attention deficit disorder. Why is all this important? This is important because these disorders are treatable. The number of additional kind of brain, recognized brain conditions in these children, once again, 22% of the individuals with autism had one of them, 30% had two, and 20% had three. Why is this important? Because all three are treatable. So, if we go back and we look at the tip of the iceberg, this is what we have to do for each individual child, adolescent, or adult who presents with the tip of the iceberg, the behaviors that you and I can see. We have to understand what is underneath the surface of the water for each, and it can vary for each child. It might be that a particular child's either new onset or worsening of pushing and hitting is due to very severe impairments in social judgment, unawareness of feelings of him or herself and others, sensory misperceptions, impaired cognitive processing, it could be due to a new onset of a psychiatric disorder and new psychosocial stressors. For the most effective treatment of the child, this given child or any given child, all of the things under the surface of the water need to be targets of treatments, not just one. And for a given child it might be different. 

It might be that under the surface of the water driving the impairing emotional changes or behaviors there are medical problems. So, there can be a whole host of things driving the behaviors which you and I see. As I mentioned, there are no medications, and for the majority of individuals with autism, there's no cure for the autism itself that can completely eliminate the core features of autism. A number of medications might have a mild to moderate effect on some of the features of autism, but these disorders are, for the most part, treatable. And what I found over the years is that when they are not recognized, the child, adult, or adolescent is living with much more impairment than they need to live with. When these other disorders are treated, the autism might not go away but life significantly improves, and that's major. As the parents know, any small improvement in your child or your grandchild is huge, and we want as many of those small or large improvements as possible. A number of medications used very carefully, only when needed, in the smallest effective dose are safe and can be very, very helpful to individuals with autism. Medication is never the only answer. So, what has gone wrong in the brain during development in autism? Brain imaging, as Marcia pointed out, a really core feature of the Waisman Center, allows us now to examine the brain in ways that were never ever, ever possible before. 

This is what you look at when you see the brain. The detail is unbelievable. But then can you imagine the technology that's available nowadays to go down and to measure the functioning of all these different neuro networks, to measure their structure, to measure connectivity in different areas of the brain. This is a chart, and I ask you just to look at the top row of boxes. As you can see, we are dealing with autism, which is on your right, autism is a clinical syndrome. It is our best understanding of this disorder, but embedded in autism are going to be lots of different types of autism which, over time, will very likely be identified as individual specific disorders that all present with the clinical syndrome of autism as we know it today. We know that specific disorders and diseases of the brain are due to the middle box on the top row, alterations in structure and function of the brain. We know that alterations in structure and function of the brain are due to the box, the second to the left, of your left, they're due to pathologic processes and mechanisms. And those pathologic process and mechanisms are due to genes and other factors influencing brain development. So, the beauty of what we're able to do now, it used to be that we could only study the clinical syndrome of autism. 

We're now able to study this whole causal pathway, and that's one of the things that we're doing here at the Waisman Center and going to be doing even more. So, it's understanding the whole pathway and how genes and other factors result in pathologic processes. Understanding those pathologic processes in mechanisms, how those affect brain structure, function, and development over time and how they lead to autism, which is basically going to unlock the disorder. So, as all of you know, the greatest advances of medicine have come when we have understood the biology of any given disorder. The hope for the future is that we'll be able to use the variation in clinical manifestations to drive the discovery of the brain bases of autism spectrum disorders and complications of autism spectrum disorders, all the other things that I mentioned to you, and then use the variation in brain microstructure and functional connectivity to drive the discovery of new genes and other factors that are involved in causing the disorder and that that will lead to new treatments based upon the biology of the disorder. New treatments, not just early intervention, not just for young children but across the life span. This may seem impossible but I don't believe it is, and many of you may know that tremendous strides have been made in a disorder that is as severe or more severe than most cases of autism, and that's Rett Syndrome. So, understanding the biology of Rett Syndrome has allowed scientists, it's still experimental but a major breakthrough. Animal models of Rett Syndrome, when they are treated with a particular medicine, the Rett symptoms are reversed. So, to me, if this can happen in Rett syndrome, it can happen in autism, and that's what I wake up every day thinking and dedicating my time to. 

So, I want to thank you very much. My research group is interdisciplinary, multiple universities, many people, clinicians, pediatricians, neurologists, psychiatrists, medical physicists, computer scientists, neurostatisticians, many people, and geneticists. Many people working together to conquer autism across all those different levels. The name of our group is ISLA. ISLA was chosen, as many of you know, "isla" is Spanish for island, and we chose that name because it represents to us the islands of ability within children with autism that we seek to unlock by understanding the biology of the disorder. And this is a picture of our group several years ago. Brittany Travers, who's out somewhere, is one of the young scientists here. I'm sorry, she's not in the picture. But I want to thank you very much, and I will now take questions. [APPLAUSE]