2008 IMFAR Shows Progress in All Areas of Autism Research
for Autism Research
May 15-17, 2008
The seventh annual International Meeting for Autism Research recently concluded in London with more than 1150 researchers from around the world attending and making more than 850 presentations.
Among the countries represented were Australia, Bangladesh, Brazil, Canada, China, Denmark, Finland, France, Greece, Iceland, India, Ireland, Israel, Mexico, Norway, Portugal, Saudi Arabia, South Africa, South Korea, Spain, Sweden, Taiwan, Uganda, United Kingdom, United States, Venezuela and Vietnam.
The following are brief summaries of some of the IMFAR presentations in the areas of autism etiology, biology, diagnosis and treatment. The record number of attendees and the depth and breadth of the science presented signals that autism research is truly becoming global, with advances being made across the board. But most importantly, the science presented and discussed will help individuals and families who are living with autism by uncovering more effective means to diagnose, treat and determine the causes of autism.
Several presentations focused on the role of the environment as a risk factor for autism. Genetic risk factors may be acted upon by additional environmental factors to ultimately cause autism.
This year IMFAR hosted an educational symposium concerning links between the environment and autism.
These presentations, led by Craig Newschaffer, Ph.D., were intended to educate the community on ongoing research and current thinking in environmental health science, genetics and epidemiology that is relevant to the investigation of environmental risk factors in autism. This symposium also served to complement other presentations on environmental exposures that are being examined for links to autism, which include such factors as method of birth induction, ultrasound frequency, as well as chemical exposures found in the home.
Irva Hertz-Picciotto, Ph.D., lead investigator of the CHARGE study at UC Davis, provided an overview of epidemiologic designs to study environmental factors in neurodevelopmental disorders. She focused on epidemiologic approaches, outlining different study designs that each pose a different challenge. She also stressed the importance of connecting epidemiology to neuropathology and neurotoxicology. Her talk emphasized that timing of exposure is critical to developmental outcome, and spoke of the promise of currently ongoing studies that prospectively examine mothers and children in order to assess risk factors and match them with their ultimate outcome.
Tony Persico, M.D. from the University Biomedico in Rome highlighted the importance of a strong pathophysiological foundation to environmental research by discussing how researchers must link particular environmental exposures to the specific disruptions in biological functions that they cause.
He presented data from his own lab which examined function of the mitochondrial aspartate/glutamate transporter in brain tissue from individuals affected with autism and also discussed newly published research that pointed to a set of genes that affect immune function which he found may be dysregulated in autism.
He concluded that environmental exposures may not be necessary or sufficient in themselves for development of autism, but hypothesized that they may contribute to the apparent abrupt onset of symptoms in a subset of individuals. These groups need to be much more carefully studied.
In two final talks, Brenda Eskenazi, Ph.D. from UC Berkeley and Eric Roberts, M.D. from the California Department of Health each presented different approaches to studying risk factors from an epidemiological perspective. Dr. Eskenazi is the lead investigator on an NIEHS/EPA longitudinal birth cohort study called “CHAMACOS” which follows mothers in California who have received high levels of pesticide exposure. She assessed exposure through biological measures and self reports, and followed children from birth through development and examined the presence of PDD through assessment on the child behavioral checklist.
Her results indicated that almost 6% of these children went on to develop symptoms of PDD, and that in many of these children, a genetic mutation may account for susceptibility to pesticides. This gene, abbreviated PON, is responsible for detoxification of pesticides. Other research has studied the PON gene and found an association in families affected with autism, and the early finding by the Eskenazi group will be replicated and explored further.
In contrast to Dr. Eskenazi’s use of direct data collection on individual subjects, Dr. Roberts presented his data published earlier this year in Environmental Health Sciences that examined the rate of autism and pesticide exposure using purely administrative data, which is available almost exclusively in the U.S. through the California DDS system and geographic information systems.
Although this data provides a unique opportunity to examine different exposures and their developmental outcomes, Dr. Roberts also carefully outlined the weaknesses and limitations of this design. He found that linking exposure of pesticides through agricultural applications with birth record data supported a link between organochlorine exposure in the first trimester of pregnancy.
A number of confounding factors make this an interesting study which needs to be replicated further, especially since the number of affected children in the highest exposure group was relatively low. However, the pairing of these final two presentations, each using different approaches to examine the same question, illustrated the absolute requirement for multiple parallel approaches to studying gene x environment interactions in autism.
“Several groups are exploring the interaction between a genetic susceptibility and environmental factors. Understanding how subgroups of children may be vulnerable to specific environmental risk factors is critical for discovering the causes of autism and for developing prevention methods,” said Geraldine Dawson, Ph.D., Chief Science Officer, Autism Speaks.
This year’s IMFAR meeting highlighted both the complexity of the disorder and the international nature of genetic research. Using Autism Speaks’ AGRE samples, researchers from Japan presented the first results to suggest an autism association with a new set of genes, called ROBO, involved in neurodevelopment.
From the other end of the globe, a group of researchers at the Icelandic genomic company deCode, Inc. showed an association of copy number variations in specific chromosomal regions, validating recent findings in previous large scale genetic studies such as the Autism Genome Project.
“Because of the complexity of autism, independent confirmation of previous results is one of the most important outcomes of such large international conferences,” explained Dr. Dawson.
Many of the genetic presentations at this year’s IMFAR actually took advantage of the variable nature of autism, utilizing either the similarities or differences in individuals with autism as a way to identify genes involved in the disorder. For example, a collaborative group of researchers from Vanderbilt University and Massachusetts General Hospital for Children showed an increased association between the gene MET and subjects with autism who also presented with co-occurring gastrointestinal symptoms.
Valerie Hu, Ph.D. from George Washington University displayed a very novel approach to reducing the heterogeneity of autism by first using exploratory statistical techniques on diagnostic ADI-R data from AGRE subjects that allowed her to identify four different “types” of individuals with autism that grouped naturally together based on their symptoms. She then measured gene expression profiles of individuals from each classification, finding clear genetic differences between each of the four autism groups and controls.
“Through careful consideration of specific autism phenotypes, researchers are making significant strides in identifying genetic risk factors in autism,” said Andy Shih, Ph.D., VP of Scientific Affairs for Autism Speaks.
“These genetic risk factors will lead to knowledge of the biological pathways that have been impacted in autism.”
The conference also included a talk by Francesca Happe, Ph.D. who argued that, except in rare cases, it is unlikely that the full syndrome of autism can result from a single cause. She based her argument on twin studies that suggest that largely nonoverlapping genes acting on each of the separate traits of autism (social impairments, language impairments, repetitive behaviors). She noted that many individuals can exhibit one of these traits in isolation. In fact, one important implication of her argument is that many people who may have isolated impairments in one domain, such as social functioning, may not receive the clinical services they need.
John Constantino, Ph.D. presented a related perspective. He noted that, when autism runs in families (familial autism), it is common (significantly more so than in the general population) for clinically-unaffected male family members to exhibit features of autism, but not the full autism syndrome. This may not be true for females or for non-familial autism. This is important because it suggests that parents who have one child with autism should be vigilant for mild impairments in a second child. Dr. Constantino also showed how quantitative characterization of the autism symptoms can aid in the search for core genetic and neurobiologic components of autistic syndromes.
International Autism Epidemiology Network (IAEN)
One important technique often used to parse genetic and environmental risk factors is epidemiology. Since its inception in 2004, the International Autism Epidemiology Network (IAEN) has developed into a unique and expansive partnership of investigators representing nearly 30 countries and specializing in various areas of autism research and treatment. With the support of Autism Speaks and the Centers for Disease Control and Prevention, the network has provided a forum for international research collaboration in autism epidemiology, aimed to better our understanding of autism etiology and natural history across the globe. Approximately 70 epidemiologists and clinicians convened the fourth annual IAEN meeting at IMFAR.
As one of the results of this meeting, many of the representatives from countries that maintain large, population-based health registries joined together to form a workgroup to develop a multi-national database that will allow for ambitious, previously unfeasible research projects. Initial studies stemming from this project will look at associations between autism and pre- and peri-natal exposure to potential environmental risk factors.
Another focus of the meeting was to outline the challenges and propose solutions to standardizing epidemiologic methodology prior to initiating the studies. Overall, the presentations of autism epidemiology studies in the developing world fueled the discussion of approaches to charactere and diagnose autism across culturally diverse settings and measure the prevalence of the disorder in these territories thereby improving much needed resources.
For those studying the biology of autism, the meeting offered symposia and workshops on topics ranging from brain imaging to animal models to immunology. One of the primary biological hypotheses of autism highlighted by several at the meeting was the concept that autism may be the result of “synaptic” dysfunction.
Synapses are the parts of nerve cells that are responsible for transferring information from cell to cell. Keynote presenter Thomas Bourgeron, Ph.D. discussed discoveries from his and other laboratories that have implicated mutations in several “synapse” genes in autism. Such genes include SHANK3, neuroligin, and neurexin, all of which encode for proteins that work together to make synapses properly operate.
Such results not only help direct geneticists toward studying other “synapse” genes as potential autism risk factors but, most importantly, they are beginning to shed light on the underlying biological features of autism. The concept of altered synapse functioning is consistent with the “functional underconnectivity” theory of autism, which hypothesizes that nerve cells are not connected together as normal and that the net result is difficulty in passing information between parts of the brain, leading to the unusual behaviors collectively called autism.
Several groups presented data expanding upon the evidence for functional connectivity deficits in autism by using EEG to read electric signals between brain regions, finding them to be altered. Additionally, preliminary data from some of the first studies to use the newest brain imaging technology, Diffusion Tensor Imaging, revealed structural irregularities in the white matter, the part of the brain that ferries the electrical signals from one region of the brain to another. This is again suggestive of connectivity problems in the brains of individuals with autism.
Another major step forward this year was that IMFAR hosted its first symposium examining the relationship between autism and the immune system. Lisa Croen, Ph.D., a researcher with Kaiser Permanente, reported that some autoimmune diseases such as food allergies and rhinitis are co-morbid conditions in autism, and Paul Patterson, Ph.D., professor of biology at the California Institute of Technology, demonstrated that maternal infection, which results in the elevation of cytokines in the fetal environment, may be a risk factor for developmental disorders.
The activation of neuroglia in the brain of autistic patients was discussed by Carlos Pardo, M.D., from Johns Hopkins University, pointing to a role for the innate immune response, though this role is still undefined and requires additional investigation. William Johnson, M.D., from the University of Medicine and Dentistry of New Jersey, presented preliminary research which found that certain MHC class II molecules may be risk factors, but which interestingly appear to act on the mother rather than the child with autism.
Other data discussed at this exciting symposium involved studies on the adaptive immune response, and how the results of such studies have been variable. The symposium presenters concluded that the full range of immune functions in individuals with autism is one area that absolutely requires further exploration to determine any contributions to the condition.
Christoph Schmitz, M.D. at Maastricht University in the Netherlands and Jerzy Wegiel, Ph.D. at the NY Institute for Basic Research presented the first results of a multiyear neuropathology study termed the Brain Atlas Project. Autism Speaks’ Autism Tissue Program (ATP) began the Brain Atlas Program in 2002 with the objective of deciphering the neuropathological features of autism in multiple brain areas in order to provide us with important missing information about how autism impacts brain structure. Initial results reported by the investigators revealed substantial brain cell size differences according to the age of the donor.
The youngest brain donors with autism (age 4-7) had smaller neurons by up to 43% in certain brain regions compared to older donors with and without autism. The investigators also reported preliminary findings on the fusiform gyrus, the site of face processing in the brain, which imaging studies have shown to be less active in individuals with autism than control subjects.
So far using 7 postmortem brains from patients with autism and 10 controls, they have found significant reductions in neuron densities that in theory could anatomically account for the abnormal function found in this brain area.
The Brain Atlas Project will continue through 2009 until all regions of 28 donor brain hemispheres have been analyzed. The ATP Tissue Advisory Board members attending the meeting urged the autism community to support brain donation to further the exploration of brain development.
Family members and unaffected individuals are encouraged to register to be brain donors as well and can get more information at http://www.autismtissueprogram.org.
An important step in this direction was the launch of the UK brain donation program to complement the one in the U.S.
“Research is finally coalescing to provide testable hypotheses that can bring us to a biological understanding of autism,” concluded Sophia Colamarino, Ph.D., VP of Research for Autism Speaks.
Baby Siblings Research Consortium
Several investigators studying infant siblings of children with autism met prior to IMFAR to discuss their findings on early identification and new methods for treating at risk infants. Mark Johnson, Ph.D., Mayada Elsabbagh, Ph.D., and Geraldine Dawson, Ph.D. led a workshop titled “From Neuroscience to Intervention: Progress in the study of infants at-risk for autism.”
Scientists discussed new approaches to detecting the first signs of autism in infants using eye-tracking methods, structural and chemical brain imaging and electrophysiology. It was noted that infant sibs who go on to develop autism are more likely to exhibit acceleration in head growth starting at about 4-6 months. Infants with this unusual head growth trajectory often exhibit behavioral symptoms emerging at about 8-10 months, which include a failure to respond to name, distress reactions, passivity, a lack of eye contact and communicative babbling, and poor imitation skills.
The workshop also focused on new approaches to early intervention with infants and toddlers who exhibited emerging signs of autism. Although several different approaches were highlighted, most of these interventions shared certain common features. Most were parent-delivered and focused on facilitating early social-communicative skills within an affectively-rich parent-infant interaction. The hope is that by identifying infants at risk and providing early intervention before the onset of the full syndrome, autism symptoms can be reduced or even prevented.
During IMFAR, eleven sites of the Baby Siblings Research Consortium (BSRC) reported in further detail their combined findings on the head growth trajectory of 761 high-risk infants (with an older sibling with a confirmed diagnosis of ASD) and 400 low-risk infants (no family history of ASD). In addition to such collaborative projects, members of the BSRC each also presented preliminary data on baby siblings from age 3-9 months of age.
Researchers are using sophisticated analysis of eye tracking data and analysis of specific neurophysiological measures to interpret very early changes in attention, including shifting of attention and joint attention. In fact, a few researchers referred to the effect as “sticky” attention, as they discovered there are subtle differences in the duration of the gazes away from the mother’s face in a scene. Some of the differences are seen in children “at risk” for autism, regardless of diagnosis, and further research will better determine if these early signs may be indicative of ASD or part of a genetic liability.
Many parents have questioned whether, in hindsight, unusual motor activity may have been one of the earliest indications of their child’s disability. A group led by Carole Samango-Sprouse, Ed.D. from George Washington University is exploring whether early motor tone, as measured through a standard test of primitive motor reflex known as the head tilt reflex (HTR), can be used to accurately identify infants with neurodevelopmental disorders when coupled with the accelerated head growth already described.
Their goal is to increase the likelihood that doctors can easily spot infants at-risk for an ASD or other neurodevelopmental disorders during well-baby medical checkups.
The HTR is an extraordinarily simple exam designed to test the reflex normally developed at 9 months of age which maintain one’s head vertical when tilted off midline. The researchers tracked infants that failed to develop the HTR and who underwent unusual acceleration in head growth during the first year of life. Out of 216 babies screened, 21 infants were flagged for “at risk” status due to these two criteria and were given full neurodevelopmental evaluations. In none of these cases did the parents or pediatricians have any previous suspicions.
Their preliminary data suggests that the combination of increased head circumference and HTR may be an indicator of possibly both ASD and developmental language disorders. Given the nature of the test (quick, easy, a very early indicator, and at no extra cost to the doctors or parents), the investigators are continuing to pursue whether the “tilt test” and acceleration in head circumference may provide early “biomarkers” for a subgroup of infants at risk for developing autism or other neurodevelopmental disorders.
Interactive Autism Network (IAN)
Other current research for assessing the special needs and interests of children with autism, and parental experiences raising a child with autism, utilizes the internet and web-based methods. The Interactive Autism Network (IAN; http://www.IANproject.org), developed by a team at Kennedy Krieger and funded by Autism Speaks, is collecting information online from families of children with ASDs throughout the U.S.
The team illustrated the breadth and depth of their data by presenting on a variety of key autism research topics, each based on information by IAN families. Through this, autism researchers learned about resources IAN can provide to facilitate their crucial work. These free resources include access to the IAN dataset (currently containing information shared by families of over 8,000 children with an ASD); the launch of a new online community and workspace for autism researchers; and assistance finding qualified participants for researchers’ local studies.
With the exception of subject recruitment, which is offered only to U.S. researchers, these services are available to autism researchers throughout the world. Many international researchers at IMFAR learned about IAN for the first time and expressed an eagerness to access IAN data for their own research.
Not long ago, autism was thought not to be treatable. Many parents were told there was very little that could be done to change the course or outcome for their child diagnosed with an ASD. Fortunately, this is no longer the case as evidenced by numerous presentations given in the area of treatment and intervention.
Treatments for autism generally fall into two categories, biomedical and behavioral, and can vary by country.
Some of the biomedical treatments discussed at this year’s IMFAR included pharmacological, complementary and alternative medicine, and dietary interventions.
Behavioral studies covered such diverse topics as theory of mind training, vocal imitation training, sleep hygiene education, pivotal response and discrete teaching methodologies, and social skills training.
One discussion presented a retrospective analysis of cases in which children with autism achieved recovery status (lost their original diagnosis of autism). With new groups forming to address the medical aspects of autism (such as the Autism Speaks Autism Treatment Network and Clinical Trials Networks), it is anticipated that more research will become available targeting specific symptoms associated with autism.
As the population of adolescents and adults with autism is rapidly growing, more researchers are beginning to explore issues that affect older people with autism including puberty, sexuality, substance abuse and social relationships.
Researchers from North Shore Long Island Jewish Hospital discussed their employment of visual supports, role play, cartoons, social stories, and video modeling in weekly group sessions. Issues regarding sexuality, development, hygiene, safety and dating behavior were addressed in groups of adolescents with autism, as well as in groups of parents, resulting in improved comfort for the participants in discussing these sensitive topics and achievement of personal goals such as learning to set boundaries. Research is ongoing in terms of further curriculum development and evaluation.
Several researchers also addressed educational issues such as teacher training and integrating students with autism into a general education environment. Expanding the quality of evidence-based research in service delivery is a critical need and several researchers presented their initial findings on the efficacy of specific community-based service programs. Some researchers are now studying ways in which families access services and the strategies they use to get them. Another theme among the service research presentations included evaluations of autism resources including materials for parents of newly diagnosed children and comprehensive treatment programs. Researchers explored the use of technology-related products to aid in the delivery of services.
One exciting theme that received increased attention this year was the many ways technology can be used to provide novel forms of assessment and intervention.
Researchers from the U.S., U.K., Germany, Greece, and Israel presented findings on many new technology-related innovations. Highlights included a diverse set of computer software applications created to assist those impacted by autism.
These ranged from interactive visual scheduling systems to a variety of video games that were developed for assessing and enhancing cognitive strengths and weaknesses, improving face processing and emotion recognition, and assessing and teaching language. Personal digital assistant (PDA) technology was explored in teens with autism to teach flexibility, feelings and sensory states.
Other presenters showed detailed virtual reality platforms specially developed to study how children with autism respond to increasingly more complex visual environments, with hopes that such carefully regulated environments may ultimately be used to understand and reduce sensory overload.
New research is also beginning to focus on how robotic therapists and 3D virtual peers can be used to teach affective language intonation and make social communication more motivating for this population.
These burgeoning and innovative uses of technology carry great promise for accelerating and enhancing the pace of autism research and treatment in the years to come.
PROGRESS AND THEMES
The most often repeated theme to this year’s IMFAR meeting was the incredible amount of recent progress the field of autism has made. This sentiment was echoed perhaps most eloquently by the recipient of the 2008 Autism Lifetime Achievement award, Isabel Rapin, Ph.D., a pioneer of autism research whose career has extended almost the entire history of autism.
Dr. Rapin was praised by her colleagues for her several lifetimes worth of achievements for autism. In her acceptance speech, Dr. Rapin reflected upon the 60 years since autism was first clinically described and provided commentary about how our understanding of autism has changed and grown during her career. From the initial psychological theories, to the advent of genetic research, through the explosion of information about brain function from imaging studies, she credited most of the advances in our understanding of autism to the rise of the many unforeseen technological advances exhibited at the meeting.
As a fitting close to an extraordinary week for autism, Autism Speaks UK organized a reception for researchers, parents, and legislatures at the House of Commons, hosted by Janet Dean, MP, chair of the All-Party Parliamentary Group on Autism.
Autism Speaks U.S. was represented at this special event by Mark Roithmayr, President; Glenn Tringali, Executive Vice President of Fundraising and Development; Sophia Colamarino, Vice President of Research, and Dana Marnane, National Director of Communications and Marketing. Autism Speaks UK Chief Executive Hilary Gilfoy addressed the group highlighting the great strides being made in research around the world and in the UK, including the breakthroughs achieved by the Baby Siblings Research Consortium and the Autism Genome Project. Gilfoy’s overall message to the crowd was one of hope.
“Only two years ago, the honest answer to the question ‘What causes autism?’ was ‘We don’t know,'” said Gilfoy. “Now we can say that we have explorable hypotheses and interventions to respond to the first signs of autism.”
“Having a forum where scientists, clinicians, and parents from around the world can congregate and share findings and perspectives has really helped move the field forward,” remarked Autism Speaks’ Geraldine Dawson, Ph.D.
“There is an openness to exploring many different possible causes of autism, including both genetic and environmental factors, and an increasing emphasis on new treatments. People from around the world are joining together to accelerate the field of autism research. It was wonderful to be a part of it.”
View a recap of IMFAR day one, Thursday, May 15 here.
View a recap of IMFAR day two, Friday, May 16 here.
View a recap of IMFAR day three, Saturday, May 17 here.
View the full press release for IMFAR 2008 here.
To read individual abstracts, please visit: http://imfar.confex.com/imfar/2008/webprogram/start.html
Data presented at the annual International Meeting for Autism Research (IMFAR) is the sole responsibility of the authors. The sponsor of the annual Meeting, the International Society for Autism Research (INSAR), and Autism Speaks take no responsibility for its accuracy.
Submitted IMFAR abstracts are reviewed only to ensure that the authors will be presenting empirical data and that aims and conduct of the study, as far as can be ascertained, are consistent with international ethical guidelines for scientific research (Declaration of Helsinki).
Acceptance of an abstract for presentation at the Meeting does not represent an endorsement by the Society of the quality or accuracy of the data and their interpretation, which judgment must await publication in a peer review journal. Readers should recognize that study data presented at meetings is often preliminary and in some cases speculative, and that findings and conclusions have not undergone the rigors of a true peer review process.
The ‘cure’ for Autistics not born yet is the prevention of birth.
Fact: You can’t cure Autistics from being Autistic.
Fact: You can’t recover an Autistic from being Autistic.
[Note: Autism is NOT a disease, but a neurodevelopmental difference and disability.]
Fact: Vaccines Do Not Cause Autism.