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.
Below are just a few select studies from last Friday's 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 Two: Friday, May 8, 2009
Catherine Lord, Ph.D. (Univ. of Mich.), who is best known for having developed the current gold standard tests for diagnosing autism (the ADOS and the ADI-R), began the second day of the 2009 IMFAR meeting by exploring the ways in which autism is diagnosed and asking whether we can do better. Although reliable, she argued that these diagnostic tools should be improved such that autism severity can be measured independent of verbal abilities and intelligence. She presented a compelling case for the need by playing the audience a series of videos taken of two people with autism over the course of 15 years. Both made social skills gains during that time, despite stark differences in their verbal abilities. Factoring out verbal abilities and intelligence might help provide more effective measures of autistic traits as they change in time.
Biomarkers for Autism
Given the difficulties of precisely pinning down the diagnostic symptoms of autism, scientists would like to move from the current behavioral description of autism to a more biological one. Several presentations today explored different proteins or genetic factors that can be extracted from blood and how they related to autism and its different symptoms. Biomarker discovery may eventually lead to something like a blood test for autism, which not only would allow earlier and potentially more reliable diagnoses of autism, but would also help researchers achieve an understanding of the biological basis of the disorder.
Several presentations today looked for such markers, ranging from particular proteins that promote growth in the brain to versions of genes important for social behavior. Two studies from the lab of Valerie Hu, Ph.D. (GWU Medical Center), delved into the intricate mechanisms that control how genes are turned on or off. She finds distinct differences in gene activation between those with autism and those without – even among identical twins – and the data presented today pointed to two different ways that these different gene activation profiles can come about. One involved a process known as DNA methylation, which marks genes to be turned off; another involved small molecules of microRNA, which bind to specific genes to turn them off. Interestingly, genes targeted by the microRNAs in this study included those involved in both the nervous system and the gastrointestinal system, taking a step toward developing a biological link between individuals with autism and the gastrointestinal problems they often experience.
The search for biomarkers may also identify various subtypes of autism, who could differ not only in their causes, but also in what treatments they will respond to. As just one example of how specific biology can dictate treatment, Diane Chugani, Ph.D. (Wayne State Univ. School of Medicine), presented data collected through molecular imaging to show that children with autism under the age of six have lower levels of the neurotransmitter serotonin in their brain. After treatment with buspirone, which boosts brain serotonin levels, those children who had the lowest levels of serotonin at the beginning were those that showed the greatest improvements in the core autism domains of social behavior and stereotyped behaviors. Similarly, Thomas Owley, M.D. (Univ. of Illinois, Chicago), presented work showing that whether a person with autism benefited from a drug called escitalopram to reduce irritability depended on the specific genetic variant of the serotonin transporter they carried. Such studies linking specific biomarkers with treatment outcomes will be essential for elucidating the subtypes of autism and tailoring treatments accordingly.
Sleep in Autism
Recognizing that sleep difficulties affect many individuals with autism, in a special early morning session organized by Beth Malow, M.D. M.S. (Vanderbilt Univ.), and Amanda Richdale, Ph.D. (Olga Tennison Autism Research Center, Australia), scientists gathered to identify the key issues in understanding and improving sleep disturbances. The researchers discussed how it was important to distinguish medical causes for sleep difficulties – such as discomfort from an upset stomach – from causes related to a dysregulation of the nervous system potentially involving circadian rhythms. They also talked about developing technologies for measuring sleep as unobtrusively as possible, as well as behavioral and pharmacological treatments that improve sleep, including the need for guidelines surrounding the use of melatonin as a sleep aid.
A presentation by Suzanne Goldman, Ph.D. (Albert Einstein College of Medicine), described more accurately the type of sleep difficulties that beset some people with autism, using data obtained from an actigraph, which is a wristwatch-like device that measures movement that occurs when people "toss and turn" from restless sleep. According to the actigraph data, the subset of individuals with autism who are poor sleepers took longer to fall asleep and their sleep was more fragmented throughout the night. Importantly, she found that these sleep patterns could modulate daytime behaviors: poor sleepers had more repetitive behaviors and hyperactivity than good sleepers with autism. Although sleep difficulties are not a core feature of autism, addressing them is likely to have a very positive and immediate impact for the person with autism and their families.
Innovative Technologies Demonstration Session
A special session organized by Autism Speaks provided live demonstrations throughout the day of 30 different innovative technologies designed to help people with autism and their families. Scientists showed how recent advancements in video and audio capture technology, web-based data collection methods, robotics, and virtual reality can be readily adapted to provide tools to help with the intervention and daily planning needs of people with autism and their caregivers.
When considering a diagnosis of autism, getting a clear picture of a child's behaviors in the clinic can be challenging. Christopher Smith, Ph.D. (SARRC), and his colleagues have developed a way to upload videos taken by parents at home to a central database. These videos allow the child to be observed for longer periods in a more natural setting rather than in a clinic. Once uploaded, clinicians can tag and annotate behaviors that are consistent with autism. In a pilot study, this method proved as reliable as the standard procedures for diagnosing autism in a clinic.
Jeff Munson, Ph.D. (Univ. of Wash.), presented a system that can track the eye gaze of nonverbal children with autism, which can be utilized to better understand their cognitive abilities. Using four infrared cameras and 3D real time graphics, he designed a virtual environment for children to explore and interact with. This can expand the limited number of tools that provide insight into the abilities of nonverbal children, and uniquely turn the tables from an examiner-driven assessment to a child-driven experience.
Casey Wimsatt, (Symbionica), demonstrated FaceSay, a social skill intervention that children play like a game using a touch pad screen to match faces or morph them into different expressions. In this set-up, children get to practice social skills by helping faces on the screen change their expressions, rather than being pressured to perform facial expressions themselves. In a preliminary sample of children 6-14 years old, using FaceSay led to gains in emotional cognition that even extended to the playground.
Although autism can now be diagnosed by an expert clinician as early as two years of age, the average age of diagnosis in the U.S. is actually much higher, according to a presentation by David Mandell, Sc.D. (Univ. of Penn. School of Medicine). Based on the review of over 70,000 Medicaid records of children under the age of nine who received an autism diagnosis, this first nationwide survey found the average age of diagnosis to be five years old. The number varied across the country, however, depending on state and county medical resources and policies. This research illuminates that even with powerful tools for diagnosis, without appropriate infrastructure to implement them we will not be in position to intervene at the earliest ages of the disorder.
An epidemiological risk factor survey by Richard Schmidt, Ph.D. (Univ. of Calif. Davis), found that taking folic acid supplements prior to and immediately following conception may have a protective effect against autism. By asking mothers to recall their folic acid intake during this time, including supplements, vitamins, and fortified cereals, the researchers found that mothers who gave birth to typically developing children took about 100 micrograms more folic acid than those who gave birth to children who later developed autism. This preliminary data would suggest that folic acid decreases the risk of the child developing autism by half, but research is continuing to examine whether other health factors like diet or smoking may be associated with this result.
Looking for other factors that decrease risk for autism, Andrew Zimmerman, M.D. (Kennedy Krieger), pursued a very unusual hypothesis regarding whether sickle cell disease, which is found in 1 out of 500 African-Americans, might confer a protective effect. Sickle cell disease compromises the oxygen carrying ability of red blood cells. This might promote mitochondrial mechanisms inside cells to help them cope with an oxygen-deprived environment, and Dr. Zimmerman reasoned these same mechanisms may mitigate the effects of autism-related damage to cells in the brain. If true, then sickle cell disease should occur less frequently in autism. However, he found that 4 out of 1216 African-Americans with autism also had sickle cell disease. This was not significantly different from the frequency expected in the general population of African-Americans, and so did not support the idea of a protective effect of sickle cell disease in autism.
People with autism frequently have unusual responses to sensory stimuli, such as lights, sounds or smells. These sensitivities may reflect sensory processing difficulties in the nervous system, and can hinder a person's comfort in the environment and interactions with others. Alison Lane, Ph.D. (Ohio State Univ.), described the patterns of sensitivities in 54 children with autism, and found that a majority of them were hypersensitive to auditory sounds or engaged in sensation seeking like hand-flapping. Most interestingly, certain sensory sensitivities were also associated with the severity of autism traits; for example, there was some evidence that those who were particularly sensitive to taste or smells had the greatest communication impairments.
Any parent of an individual with autism knows too well that these sensitivities extend to the realm of food. Another presentation by Linda Bandini, Ph.D. (UMass Medical School), confirmed that the eating patterns of children with autism were indeed especially picky: children with autism refused more foods and ate a narrower range of foods than typically developing children would eat. When analyzing the components that influenced the restrictive diets, the researchers found children with autism refused foods based on the temperature, texture, shape, or even brand, of the food, as well as the color of the food or whether foods were touching each other. Overall, food refusal was correlated with oral sensitivity. Research into the sensory difficulties of people with autism not only provides a window into how their nervous systems are organized, but can also lead to ways to help manage their sensitivities.
View a recap of day one, Thursday, May 7 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