The Eighth Annual International Meeting for Autism Research (IMFAR), held this year in Chicago, Ill., kicked off on Thursday with scientists from around the world gathering to share their latest research information. The goal of those in attendance is to use research methodology to develop means of helping individuals living with autism and their families have a better quality of care and life.
Throughout the day there were over three hundred presentations in oral or written form. Some of the many themes of the first day's sessions included psychiatric co-morbidity issues, intervention methods, oxidative stress, and the role of under-studied neural networks in autism such as the motor system. Below are just a few select studies from last Thursday's many presentations. A full report of the conference will be issued in Autism Speaks e-speaks newsletter this week. Click here to register for e-speaks.
Highlights from Day One: Thursday, May 7, 2009
Mark Bear, Ph.D. (MIT), opened the conference with a keynote address that demonstrated how understanding the basic workings of the brain can lead to potential treatments for autism – some of which, he explained to the audience of over 1400 – are being tested today. As a neurobiologist, his research to understand the role of connections between neurons, called synapses, led him to study Fragile X syndrome, a genetic disorder that is frequently accompanied by autism. The syndrome is caused by a mutation in a single gene, that results in the loss of a protein called FMRP, which is critical for slowing down the manufacture of other proteins at synapses. Without FMRP, protein synthesis goes into overdrive. Dr. Bear has shown that a drug that interacts with a specific type of receptor at the synapse (called the metabotropic glutamate receptors) can put the brakes on this runaway protein synthesis, and reverse autism-like behaviors in mice engineered to have the Fragile X mutation. Similar drugs are now being developed and tested for people with Fragile X.
As Dr. Bear led the audience through the research and thought processes that have brought scientists from the discovery of the Fragile X gene to clinical trials in less than 20 years, he suggested the approach may work for other causes of autism, too, because other single gene mutations responsible for genetic syndromes showing features of autism all involve the same pathways governing protein synthesis in a cell. Dr. Bear hypothesized that the vast majority of autism cases for which a genetic cause is currently unknown may similarly result from perturbations to protein synthesis at synapses. If different mutations all have a similar effect at the synapse, this would provide researchers with a shortcut in designing treatments.
Dr. Bear was introduced by Autism Speaks Chief Science Officer Geri Dawson, Ph.D., who announced their 2009 Strategic Plan for Science. The Autism Speaks Strategic Plan, developed in consultation with its Scientific Advisory Committee and outside advisors, is focused on innovation and an emphasis on translating discoveries into diagnosis and treatments for individuals living with autism today. View the plan here: www.autismspeaks.org/science.
Psychiatric Issues Common in Autism
Disentangling psychiatric disorders from the core symptoms of autism is of critical importance because current treatments for these conditions can potentially improve function and quality of life for people with autism, and this provided another central theme throughout the first day of the meeting. Tony Charman, Ph.D. (Institute of Child Health, UK), reported that two-thirds of children with autism (10-14 years old) also have at least one psychiatric disorder, such as social anxiety disorder or ADHD, which impairs their function beyond that due to autism. He argues that these conditions are six times more frequent than in the general population, and that people with autism should be routinely screened for them. Many other presentations today supported this view, finding evidence for obsessive compulsive disorder, mood disorders, specific phobias, as well as anxiety disorder and ADHD in people with autism. One presentation in particular emphasized the idea that these disorders are indeed separate from autism. Deborah Fein, Ph.D. (Univ. of Conn.), presented data from her studies of individuals who have recovered from autism. Interestingly, she finds that although they had lost their autism diagnoses, 80% of these individuals had psychiatric disorders, most commonly anxiety or ADHD. (Read an Associated Press story about Dr. Fein's research here; international coverage here.)
Progress in identifying the earliest signs of autism has created the need for intervention methods adapted for very young children, and two sessions were devoted to presenting research currently in progress to measure the success of a variety of intervention strategies. Rebecca Landa, Ph.D. (Kennedy Krieger Inst.), reported the effectiveness of a classroom-based intervention for two year olds. Delivered by a teacher and supplemented with parent education on the core teaching goals, the intervention lasted for six months, after which many children had made gains in cognitive function and language abilities. These gains could last six months or more afterwards. For even younger ages, Jessica Brian, Ph.D. (York Univ.), presented a newly developed "Social ABCs" intervention that was given to babies 14-18 months old. Parents were trained to administer this intervention, which was based on Pivotal Response Training. After six months, gains were apparent in communication skills, and parents reported it was practical to implement the intervention in their homes. Throughout the day scientists reiterated that parental involvement in these interventions, particularly at such young ages, is an increasingly important and promising avenue for autism treatment.
Another study by Brian Reichow, Ph.D. (Yale Univ.), and colleagues compared the effects of behavioral and naturalistic strategies on speech development in preverbal children with autism (3-6 years old) who had fewer than 10 spoken words. Behavioral strategies reinforce correct responses that a child gives when prompted by a teacher, for example, to imitate a movement. Naturalistic approaches seek to instruct through play-based routines that use objects or activities that are highly motivating to the child with autism. After 12 weeks, children in each type of intervention made similar gains in the frequency and diversity of words spoken. In both groups, however, there were children who did not benefit, raising the possibility that they might respond to a different intervention style. These preliminary results were based on very small number of children, and further research will help scientists form a better idea of the benefits of these two approaches.
As families have no doubt discovered, the increased prevalence of autism has led to a shortage of autism therapists. There is a great need to find methods to train new ones, especially in communities that may not be fortunate to have many service providers. One presentation by Laurie Vismara, Ph.D. (M.I.N.D. Institute), found that additional therapists could be trained at a distance by using technologies now readily available, including teleconferences and print and video materials provided on a DVD. A range of professionals (psychologists, speech language pathologists, occupational therapists, case managers) and parents were trained on the Early Start Denver Model intervention. Through this distance "learning package," improvements in therapist and parent skill use were associated with gains in social imitation and attention by children with autism.
Oxidative Stress in the Brain
Several presentations at the meeting explored the possibility that the brains of people with autism are under oxidative stress that exceeds normal levels. Oxidative stress is a condition in which reactive oxygen molecules, called free radicals, form inside the cell and overwhelm the proteins that normally quench them, leading to cell damage and even death. One very preliminary study by Elizabeth Sajdel-Sulkowska, Ph.D. (Harvard Medical School), looked directly at postmortem brain tissue for evidence of oxidative damage in two individuals that had had autism. Using a molecular marker called 3 nitrotyrosine, she found signs of oxidative damage in multiple brain areas, including regions important for speech and emotional and cognitive processing.
Excess free radicals may result from malfunctioning mitochondria, the energy powerhouses of cells. This fact, combined with a small number of autism cases shown to also have mitochondrial disorders, spurred Jacob McCauley, Ph.D. (Univ. of Miami), to search for mitochondria-related gene variations associated with autism. When scanning the DNA localized to mitochondria, no genetic variations were associated with autism; however, when scanning DNA taken from the cell nucleus, which contains instructions for the rest of the cell as well as some mitochondrial proteins, the study confirmed an association previously found between autism and a protein that transports molecules in and out of mitochondria. Future detailed studies are planned to look DNA base pair by DNA base pair at the entire mitochondrial genome for variants linked to autism.
Finally, oxidative stress may also be caused by over-activation of the immune system. One presentation by Mazhar Malik, Ph.D. (NYS Institute for Basic Research in Developmental Disabilities), and colleagues showed that several immune system molecules, called cytokines, were elevated in brain samples from people with autism, indicating a potentially damaging inflammatory response. Many other studies exploring the link between the immune system and autism will be presented in the next two days of the meeting.
Predictors of Outcome
Faced with a range of interventions and enrollment in school, parents often wonder if characteristics of their children can predict how they'll fare in the future. For example, some children make large developmental gains when given 20-40 hours per week of early intensive behavioral intervention, but some do not. Before undertaking such an intensive (and expensive) route, it would be of great use to know which children are likely to respond. To this end, Tristram Smith, Ph.D. (Univ. of Rochester), presented data on 71 children before and after a year long intensive behavioral intervention, and found that those who had some social communication abilities beforehand were more likely to benefit. In contrast, repetitive behaviors did not predict any outcomes.
Several other research presentations focused on discovery of other types of predictors. For example, Vanessa Rivera (Univ. of Wash.) and her colleagues reported on predictors for academic achievement in school. Fewer problem behaviors at age 6 predicted better spelling at age 9; similarly, higher social skills predicted better word reading at age 9. This type of study can help pinpoint key skills needed to maximize the benefit for a child with autism in a school environment.
Finally, Teri Todd, Ph.D. (Calif. State Univ.), and colleagues showed that adults with autism report more satisfaction and have fewer on the job problem behaviors when their employment directly fits their interests. In a community in northern California, nine micro-businesses were formed based on the interests of adults with autism, including a yard maintenance service, a bird feeder service, even a mobile document shredding service. This demonstrates that with a person-centered approach and some creative thinking, adults with autism can be included in the community in meaningful ways.
Although autism is most often thought of as a disorder of social function, it involves a wide array of brain systems. During the first day of the conference entire sessions were devoted to the study of both sensory and motor systems in autism. One study presented by Gianluca Esposito, Ph.D. (Univ. of Trento, Italy), suggests that movements made by a five-month-old infant can signal that something is amiss in the brain and distinguish children who will go on to develop autism. By analyzing home videos of infants lying on their backs, he found that those who later developed autism more frequently assumed an asymmetric position, with arms or legs unmatched, than did the infants who were typically developing or developmentally delayed.
Another presentation by Stewart Mostofsky, M.D. (Kennedy Krieger Inst.), showed that children with autism learn movements differently than do typically developing children. To reach out and touch a target accurately, for example, the brain commands the arm to move, then evaluates the arm position relative to the target using vision and proprioception – a sense of the arm's position in space that is registered through touch receptors in joints and muscles. This study found that in contrast to typically developing children that mainly use visual feedback to target their movements, those with autism rely primarily on proprioceptive cues when performing a reaching task. Harnessing the differences in how people with autism learn may build their movement skills, which not only improves coordination, but enhances their imitation abilities, which are thought to be crucial for understanding the actions of others. Moreover, Marianna Murin, Ph.D. (Great Ormond Street Hospital for Children), even found that a small but significant cause of peer-rejection of high-functioning individuals with autism is related to their motor difficulties, thus highlighting the need for increased attention to motor skills in autism.
View a recap of day two, Friday, May 8 here.
View a recap of day three, Saturday, May 9 here.
Read a press release about the conference here.
View press coverage of the conference here.
To read individual abstracts, please visit: http://imfar.confex.com/imfar/2009/webprogram/start.html