Makiko Kaga, M.D. was clearly nervous. She told me so, several times.
Dr. Kaga is the Director General of the Japanese National Institute of Mental Health at the National Center of Neurology and Psychiatry (NCNP). She is also our collaborator and the main organizer of the “Joint Academic Conference on Autism Spectrum Disorders” that Autism Speaks co-hosted December 1-3, 2011 in Tokyo, Japan.
She and her team of about a dozen junior faculty, post-docs and graduate students had been working feverishly preparing for the conference. In this first academic conference of its kind devoted to autism, Autism Speaks brought six leading autism researchers from the U.S., with expertise ranging from epidemiology to intervention, to share their work, including unpublished results, and to explore collaborative opportunities with their Japanese counterpart. Dr. Kaga’s team was charged with coming up with the right mix of presentations by Japanese and U.S. scientists that would ease productive exchange and interactions. From my own experience, this is easier said than done, especially with language and cultural differences. Plus, you never really know how well things will flow and gel until it happens.
Around the same time, Masatsugu Tsujii, Ph.D. and Teruko Ujita of Japan Developmental Disabilities Network (JDD-Net) were having similar jitters. Working together with Autism Speaks’ communications manager Danielle Yango and Alison Bradley, from our international PR firm BLJ, they were responsible for staging awareness activities throughout the three-day conference, concluding with an awareness event involving Yoko Ono. Ms. Ono is Autism Speaks’ Global Autism Awareness Ambassador and she kindly agreed to take time from her busy schedule to join many Japanese families and professionals to raise awareness about autism.
Teruko Ujita is a mom, and the Executive Director of JDD-Net. She is one of those super effective people who, no matter how chaotic things get around her, is always calm and ready to flash a big smile. Autism Speaks’ collaboration with the Japanese autism community really started about 18 months ago with a chance meeting between Dr. Tsujii and I at IMFAR 2010. So to say he was feeling the pressure to deliver is probably an understatement.
A couple of times during those tense hours, various people mentioned “Lost in Translation,” the cult Sophia Coppola film starring Bill Murray about feeling dislocated in the Japanese culture. Each time I muttered “shut up” under my breath, not wanting to be drawn into the whirlpool of anxiety around me.
In the end, we really didn’t have to worry. Or rather, maybe because all our wonderful colleagues obsessed so much over every detail, both the academic conference and the awareness event with Yoko Ono unfolded brilliantly. Both Japanese and U.S. researchers told me how much they learned at the conference, and how they plan to follow up and explore collaborative opportunities in areas like early screening to environmental sciences. I knew everything was going to be OK with the awareness event when right before Yoko Ono took the stage for an hour of inspirational remarks and TV and press interviews, she was smiling and clapping watching Salsa Gum Tape, a band comprised of individuals with disabilities, along with a packed hall of families and professionals performing a rousing interpretation of John Lennon’s “Imagine.”
This is a post by Alex Plank, founder of Wrong Planet.
I sat down with Liz Laugeson of UCLA’s PEERS program to talk about how to make friends. Making friends can be hard for individuals with Autism / Asperger’s because we have a hard time figuring out social cues.
A lot of the social skills training I’ve run across focus on concrete skills like introducing yourself. These skills are great in theory but autistics like myself often struggle with figuring out what actually works in practice. The PEERS program, however, seems to be based in real life application of social skills.
I’m sure you’re going to enjoy my interview with Liz!
The Autism Speaks’ Innovative Technology for Autism (ITA) Initiative has awarded more than $400,000 in new research grants to develop innovative assistive, educational, therapeutic, and diagnostic technologies for persons with autism.
2011 saw a new approach for Autism Speaks’ Innovative Technology for Autism(ITA) Initiative with the running of a student design competition called Autism Connects. The design brief was pretty straight forward: to create technology design ideas for individuals with autism to better connect with the world around them, and to allow individuals who do not have autism to better understand and connect with those who do.
This is a guest post by by Mehreen Kouser, a Dennis Weatherstone Fellow, and Ph.D. Candidate working with Dr. Craig Powell at the UT Southwestern.
This year IMFAR hosted a Scientific Panel titled “Shank synaptic genes in autism: Human genetics to mouse models and therapeutics” organized and chaired by Dr. Craig Powell. This panel consisted of four presentations starting with the unequivocal role of Shank3 in autism and ending with potential treatment strategies in genetically mutated mouse models of Shank3.
Over the past few years , Shank3 has emerged as the new “it” gene for autism. Current estimates suggest that Shank3 errors account for 0.5-2 % of autism diagnoses making it a major genetic cause of autism. Several recent human studies have implicated mutations/deletions/duplications in the Shank family of proteins, especially Shank3, to be involved in ASD and 22q13 Deletion Syndrome. Shank3 is a scaffolding protein that is involved in synapse architecture. Mutations in Shank3 are known to affect synaptic connections between neurons in similar ways to other autism-relevant genes such as neuroligin and neurexin. Thus understanding the role of Shank3 in autism is critical.
The first presenter at this panel was Dr. Catalina Betancur from INSERM in France. Dr. Betancur was a major player in the discovery of Shank3’s relevance to autism. She carefully detailed all known human mutations, deletions, and duplications published since the first paper on Shank3 mutations in idiopathic autism was published in 2007.She also outlined the case for Shank3 as a major causative gene in the symptoms of the 22q13 chromosomal deletion syndrome known as Phelan-McDermid Syndrome. In addition, Dr. Betancur detailed the work of her laboratory and others implicating Shank2, another member of the Shank gene family, in autism.
Dr. Joseph Buxbaum from Mount Sinai School of Medicine in New York was the next presenter. His laboratory was the first to publish a genetic mouse model of Shank3 successfully Shank3. Their Shank3 mutant mouse closely mimics autism-associated mutations in this area of the Shank3 gene. His work focused on the heterozygous mutation of Shank3 gene as this is the state of autism patients with Shank3 mutations. Characterization of this mouse model, clearly suggests that Shank3 plays an important role in synapse architecture, function, and plasticity. Among the most intriguing findings in his presentation was his ability to reverse the manifestations of Shank3 mutation in brain slices treated with Insulin-like Growth Factor-1 (IGF-1). This gives us the much needed hope that Shank3 mutation models of autism will lead to identification of novel therapeutic targets that can be validated in these models.
Next, Dr. Yong-hui Jiang from Duke University in North Carolina presented his work on a genetic mouse model very similar to that of Dr. Buxbaum’s group, but his focus was the homozygous mutation of Shank3 mutating both copies of the gene. He noted that the Shank3 gene is more complex than originally thought, with potentially having as many as six variants or isoforms. His careful analysis of this mutant model clarified that only a portion of Shank3 isoforms are affected by this genetic strategy. He identified abnormalities in synaptic connection morphology in his model. Moreover, his lab characterized this mouse model extensively on autism related behaviors and found them to be impaired in the social behaviors, repetitive behaviors, communication, motor coordination and learning and memory. These results demonstrate that human diseases can be successfully modeled in mice. The hope is that if we can reverse them in mice, treatments for humans are not far away.
Dr. Joao Peca from Guoping Feng’s lab at MIT in Massachusetts concluded the session by presenting a completely different Shank3 mutation in mice. He began his presentation by telling us about another synaptic gene called SAPAP3 and showing us its involvement in a repetitive grooming behavior in mice. He showed that SAPAP3 knockout mice continuously groom themselves and that this behavior can be reversed by putting this gene back into the striatum of mice later in life. He also showed that Shank3 is a strong binding partner of SAPAP3 and their Shank3 mutant mice have the same increase in repetitive grooming behaviors. Like the other Shank3 mutations, this mutant does not affect all forms of Shank3, but may mimic a different human mutation.
This panel set the stage for future advances in the area of Shank3 and autism. Only 4 years after the initial study implicating Shank3 in autism, we now have at least 3 different animal models and 4 publications on these models. Although, we may face grave challenges in sorting through the heterogeneity of mutations, deletions, and duplications and their different consequences, these presenters clearly demonstrate that this strategy will lead to identification of potential therapeutic targets that can be readily tested in animal models.
by Alycia Halladay, Ph.D, Director of Environmental Science
Research using identical and fraternal twins is typically used to identify genetic influences on the development of ASD. This year, researchers studied a large group of twins and examined the concordance of different types of symptoms (1). Using this approach, the researchers found that the concordance of severe autism between identical twins and fraternal twins was about the same, indicating a strong environmental component to ASD severity. But what are those environmental factors? Epidemiological studies are providing clues.
At this year’s IMFAR, new data was presented that focused on studying groups of people and their exposures to a number of environmental factors. Each used different designs with their own unique advantages. For example, at UC Davis, the CHARGE study (www.beincharge.ucdavis.edu) examined the risk of developing autism following exposure to a number of factors that were identified through self report or medical records. Those that showed an association were antidepressant SSRI use (2) and metabolic disorders including hypertension and diabetes (3). On the other hand, a previously identified factor, maternal infection, was not associated (4). Why not? The researchers suggested that fever, not infection per se, may be a factor. Using self-report and medical records obtained prior to study entry may not accurately capture all relevant information, and an infection or fever may be missed in some reports. However, other types of information, such as method of birth, is easier to gather accurately. An analysis revealed that non-emergency or elective c-section deliveries did not show a significant association with autism, addressing a concern that many public and community stakeholders have expressed (5).
As an alternative to retrospective reports, the Early Markers of Autism Study in California is obtaining samples of blood from pregnant women by obtaining extra blood taken during the alpha-fetal protein screen that is banked. Not all states bank these samples for research, so this is a unique resource. By examining the levels of mercury in blood taken during pregnancy together with newborn blood spots, the researchers can get a more comprehensive picture of the prenatal environment. They reported no difference in mercury levels compared to those of non-affected children during gestation, and also reported no difference in thyroid hormone levels (6,7). Examination of subgroups of autism with regression did not change the results. While these data are incredibly novel and valuable, these studies were not designed to capture information throughout the entire pregnancy nor capture factors after birth
Another way to study exposures during pregnancy is through birth certificate data. In some states, the birth certificate contains information such as the place of birth and the occupation of the mother and the father. Using this information, scientists found that occupational exposures in mothers to certain chemicals resulted in an increased risk of ASD in offspring (8).
While each approach brings unique strengths, all researchers agree that the most comprehensive way to capture all information accurately, is a prospective design. This means identifying children as soon as possible and following them from that point on to gather every piece of relevant information from medical reports to blood samples. Autism Speaks is proud to co-sponsor such a study: the Early Autism Risk Longitudinal Investigation (EARLI). This groundbreaking project will provide even more answers to what causes autism, and needs the help of the community to do so.
So how can researchers blend or expand their research if they are using only one type of design? Autism Speaks and the National Institutes for Environmental Health Sciences are sponsoring a network of projects called the Environmental Epidemiology of Autism Research Network (EEARN). The goal of this network is to improve communication among researchers in this field, identify opportunities for collaborative projects and improve research tools for both existing, and new projects. Over 20 studies from 8 countries are represented in the network. We will keep you updated on the activity of the network, and we hope you will keep checking in for updates.
1. Understanding Clinical Variability In Autism: Results From a California Twin Study. W. Froehlich*1, S.
Cleveland1, A. Torres1, J. M. Phillips1, B. Cohen2, A. Fedele3, T. Torigoe2, J. Collins4, K. S. Smith5, L. Lotspeich1, L. A. Croen4, S. Ozonoff6, C. Lajonchere7, J. K. Grether5, N. Risch8 and J. Hallmayer1, (1)Stanford University, Stanford, CA, (2)Autism Genetic ResourceExchange, Los Angeles, CA, (3)Autism Speaks, Westmont, NJ,
United States, (4)Kaiser Permanente, Division of Research, Oakland, CA, (5)California Department of Public Health, Richmond , CA, (6)UC Davis MIND Institute, Sacramento, CA, (7)Autism Speaks, Los Angeles, CA, United States, (8)University of California San Francisco, San Francisco, CA
2. SSRI Use During Pregnancy and Risk of ASD or Developmental Delay In Children. R. A. Harrington*1,L. C. Lee1, C. K. Walker2, R. L. Hansen3, S. Ozonoff3 and I. Hertz-Picciotto4, (1)Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, (2)Department of Public Health Sciences, University of California at Davis, Davis, CA, (3)MIND Institute, University of California at Davis, Sacramento, CA, (4)Department of Public Health Sciences, University of California Davis, Davis, CA
3. The Role of Maternal Diabetes and Related Conditions In Autism and Other Developmental Delays. P. Krakowiak*1,2, A. A. Bremer3, A. S. Baker1, C. K. Walker1,4, R. L. Hansen2,3 and I. Hertz-Picciotto1,2, (1)Public Health Sciences, University of California, Davis, Davis, CA, (2)M.I.N.D. Institute, Sacramento, CA, (3)Pediatrics, University of California, Davis, Sacramento, CA, (4)Obstetrics & Gynecology, University of California, Davis, Sacramento, CA
4. Prenatal Influenza or Fever and Risk of Autism/Autism Spectrum Disorders. O. Zerbo*1, I. Hertz- Picciotto2,3, A. M. Iosif4, R. L. Hansen5,6,7 and C. K. Walker8, (1)Sacramento, CA, (2)University of California, Davis, Davis, CA, (3)Department of Public Health Sciences, University of California Davis, Davis, CA, (4)UC Davis, Davis, CA, (5)University of California, Davis, MIND Institute, Sacramento, CA, (6)MIND Institute, University of California at Davis, Sacramento, CA, (7)MIND Institute and Dept. of Pediatrics, University of California Davis, Davis, CA, (8)Department of Public Health Sciences, University of California at Davis, Davis, CA
5. Cesarean Birth and Autism Spectrum Disorder. C. K. Walker*1, P. Krakiowiak2, A. S. Baker3, R. L. Hansen4, S. Ozonoff5 and I. Hertz-Picciotto6, (1)Obstetrics & Gynecology, UC Davis, Sacramento, CA, (2)Public Health Sciences, UC Davis, Sacramento, CA, (3)Public Health Sciences, UC Davis, Davis, CA, (4)Pediatrics, M.I.N.D. Institute, UC Davis, Sacramento, CA, (5)Psychiatry and Behavioral Sciences, M.I.N.D. Institute, UC Davis, Sacramento, CA, (6)Public Health Sciences, M.I.N.D. Institute, UC Davis, Davis, CA
6. Prenatal and Neonatal Peripheral Blood Mercury Levels and Autism Spectrum Disorders. L. A. Croen*1, M. A. Lutsky1, C. Yoshida1, C. P. Alaimo2, M. Kharrazi3, J. K. Grether4 and P. Green2, (1)Kaiser Permanente Division of Research, Oakland, CA, (2)Civil and Environmental Engineering, Univ. of California Davis, Davis, CA, (3)Genetic Disease Screening Program, California Department of Public Health, Richmond, CA, (4)California Department of Public Health, Richmond, CA
7. Prenatal and Neonatal Thyroid Stimulating Hormone Levels and Autism Spectrum Disorder. M. A. Lutsky*1, C. Yoshida1, B. Lasley2, M. Kharrazi3, J. K. Grether4, G. Windham4 and L. A. Croen1, (1)Kaiser Permanente Division of Research, Oakland, CA, (2)Department of Population Health and Reproduction, UC Davis, Davis, CA, (3)Genetic Disease Screening Program, California Department of Public Health, Richmond, CA, (4)California Department of Public Health, Richmond, CA
8. Autism Spectrum Disorders In Relation to Parental Occupational Exposures During Pregnancy. G. Windham*1, J. K. Grether2, A. Sumner3, S. Li4, E. Katz5 and L. A. Croen6, (1)California Department of Public Health, Richmond, CA, (2)California Department of Public Health, Richmond, CA, (3)Vermont Department of Health, Burlington, VT, (4)Kaiser Permanente Divison of Research, Oakland, CA, (5)Occupational Health Branch, CA Department of Public Health, Richmond, CA, (6)Kaiser Permanente Division of Research, Oakland, CA
by Geraldine Dawson, Ph.D., Chief Science Officer, Autism Speaks
In San Diego last week, The International Meeting for Autism Research (IMFAR) celebrated its 10th anniversary. Only a decade ago, prompted by parents, a small group of scientists pulled together the first IMFAR meeting. As program chair of IMFAR’s second meeting in 2002, I recall spreading the submitted abstracts out on a large conference table in my lab; working with my graduate students, we created the conference schedule by moving pieces of paper around the table’s surface! In 2007, when my colleague, Elizabeth Aylward, and I hosted the meeting in Seattle, we were thrilled that 1,000 people attended the conference. This year, only four years later, nearly 2,000 people attended IMFAR inSan Diego, representing a 10-fold increase in attendance in only a decade. The conference not only has changed in size, it has also changed in a number of other significant ways:
Autism as a global challenge
The international scope and participation has grown tremendously. Whereas the first meetings included scientists from Europe and a few from Asia, today’s IMFAR includes scientists from virtually all continents on the globe. Autism Speaks sponsors an annual meeting at IMFAR of the International Autism Epidemiology Network (IAEN), a group now comprised of over 100 scientists from 30 counties! Topics of this year’s IAEN meeting focused on how to deliver services to low resource communities, both in the U.S.and in developing countries. Travel awards were given to 13 international scientists from countries that included Oman, Turkey, Nigeria, Palestine, China, India and Argentina, among others.
Attracting a new generation of scientists
I am especially encouraged by the fact that the number of bright young graduate students and postdocs involved in autism research is rapidly growing. Graduate students and postdocs from diverse fields ranging from neuroscience to education shared their research results and had an opportunity to hear and interact with scientists from a wide range of disciplines. Thirty-seven students received travel awards to IMFAR; they travelled not only from around theUS, but also from the UK, Germany, France, Spain, Canada, Japan, Mexico, Australia, and Israel. IMFAR provides a unique opportunity for graduate students to learn and be motivated to devote their careers to autism research. I was honored to participate in the “Meet the Experts” luncheon which provided an informal venue for students to talk in depth with senior scientists about their careers and areas of expertise.
People with autism and their families have a real presence in the IMFAR meeting
The inclusion of families and individuals on the spectrum as important and influential participants in the planning and conduct of IMFAR has steadily increased over the past decade. Community members are part of every IMFAR committee as well as the program planning. The committee I chaired this year that oversaw the INSAR board elections included a mother of a child with ASD and an adult with Asperger’s syndrome. At the meeting, parents and self-advocates with ASD attended lectures, gave presentations, and made opening remarks. Families with children on the spectrum could be seen throughout the meeting and especially enjoyed the technology demonstrations and booths. Video coverage was managed by Alex Plank, a person on the spectrum who hosts the website Wrong Planet.
Scientific progress provides hope for the future
Finally, I was struck by how both the breadth and depth of autism research has increased over the past 10 years. There are so many ways in which our thinking about autism has changed dramatically. To bring home this point, here are a few of the key themes and topics of research that emerged from this year’s conference:
- We now recognize that autism affects the whole body, not just the brain. Presentations reflecting this theme focused on studies of mitochondrial dysfunction, oxidative stress, sleep, gastrointestinal disorders and nutrition.
- The role of the environment and gene-environment interactions are now recognized as important etiological factors. Examples at this year’s meeting included studies on a variety of pregnancy and prenatal factors (fertility therapies, medication use, gestational diabetes, very low birth weight, maternal infection), neurotoxins (mercury, occupational exposures, air pollution), and specific gene-environment interactions.
- Autism can be recognized in infants less than one year of age, and interventions appropriate for infants and toddlers can alter the trajectory of children’s developmental outcomes. A wide range of new and innovative methods for detecting autism in infants were presented, along with several new methods for treating infants.
- There is an increasing interest in addressing the needs of two previously under-recognized populations of people with autism: adults and nonverbal individuals. I chaired a symposium on nonverbal autism in which scientists presented findings based on EEG that demonstrated that many children with autism who are unable to speak nevertheless have strong intellectual abilities and language comprehension. The same symposium illustrated how speech-generating devices can be effectively incorporated into early intervention to promote communication in children who have not developed speech. Studies on adults with autism were diverse, ranging from those focused on intervention strategies to improve quality of life, to how to promote independence and optimal health.
- The promise that technology holds for improving the quality of life for people with autism is more and more evident. This was especially clear in Autism Speaks’ Innovative Technologies Demonstration. The session was lively as adults and children with ASD and their families tried out the games and communication devices. We sponsored an international student technology design competition that attracted over 120 entries from around the world. I had the pleasure of giving the awards to the top three designs, all of which focused on the theme of helping people with autism connect to the world around them.
- Autism is no longer a “black box” – instead, the puzzle of autism’s underlying biology is being put together piece by piece. Using information gleaned from a decade of genetic research, neuroscientists presented papers that shed light on the role of the immune system in autism, identified several neural signaling pathways affected in autism, and described strategies for helping repair the brain’s synaptic function. One of the keynote lectures focused on the promise of a new technique called “induced pluripotent stem cells” which allows stem cells to be made from skin tissue. These cells are being coaxed into forming neurons and allow scientists to compare precisely the difference between neuronal functioning between persons with and without autism. These insights and technologies are providing clues to new autism drugs which are now being tested in animal models.
While I am happy to see the remarkable progress that has been made over the past decade, I am eagerly looking forward to the next 10 years, knowing that the pace of scientific discovery will only accelerate. I am hopeful that the science of the future will allow us to continue to make even more of a difference in the lives of people with autism of all ages.
Video Credit: Alex Plank
Nancy Jones, Ph.D., Director of the Autism Treatment Network and Clinical Trials Network
In one of the final sessions at IMFAR, several presentations provided updates in three important areas of intervention and treatment research.
Using technology to make interventions more accessible
Laurie Vismara, Ph.D. from UC Davis, MIND Institute reported on a new approach to make training for families on the Early Start Denver Model (ESDM) more accessible. Typically, families and clinicians attend training and coaching sessions in person at the clinic. Using web and DVD technology, Dr. Vismara and her colleagues have developed a program where families use web-based video conferencing for training sessions with a therapist. Families also had access to an interactive DVD including modules covered in training sessions that provide summaries of the key sessions, video examples, supportive videos, and feedback exercises. The study examined how this new web-based approach compared to in-person sessions. In a small pilot group of ten families, the researchers found that parents’ ability to implement the activities from the intervention was comparable to that found in families trained in-person. Improvement in the children’s word production and imitation skills were also comparable to children whose families had in-person ESDM sessions. A manual of this web-based approach is currently being developed. This approach holds promise to make interventions accessible to more families and to ensure children get timely intervention of the appropriate intensity.
Effectiveness of melatonin for sleep disorders in ASD
Many families and individuals with ASD report sleep problems. To alleviate these sleep problems, some individuals use melatonin, a hormone that is readily available and sold over-the-counter as a supplement. But despite melatonin’s easy accessibility and wide-spread use, there are not a large number of systematic studies of its use for sleep disorders in ASD.
Beth Malow, M.D., a neurologist and sleep specialist, and her team at Vanderbilt University Medical Center (VUCM), reported results from a pilot open-label study of melatonin for improving sleep onset. Many children suffer from sleep onset insomnia, which is a delay in their ability to fall asleep. The study examined the effectiveness of using melatonin to help children (ages 3-10) who have difficulty falling asleep (more than 30 minutes delay on more than three days a week). In addition to the melatonin, all families also were provided with sleep education on how to improve sleep. Twenty-four of the twenty-five children in the study showed an improvement at moderate doses that were well tolerated, decreasing the time it took them to fall asleep on more than three days a week. This study was an open label study, which means that families were aware of the treatment they were receiving. This study provides initial evidence for the potential effectiveness and safety of the treatment and also preliminary information to guide development of a planned multi-site, randomized controlled trial of melatonin.
Arbaclofen shows potential to treat social and communication problems in ASD children with high irritability
In a previous clinical trial on individuals with Fragile X, arbaclofen was found to lessen children’s tendency to withdraw socially and improved social behavior. The study reported at IMFAR examined the effectiveness of arbaclofen in improving social and communication skills in children with ASD. The children were 6-17 years of age, had a diagnosis of autism or PDD-NOS and also had high levels of irritability. The study was an 8-week, open-label study. Craig Erikson, M.D., of Indiana University School of Medicine reported the findings of the multi-site trial. Key improvements were noted for irritability, social withdrawal and communication. A double-blind, placebo-controlled trial is planned to begin early in 2011.
Guest blogger Ruth Carper, Ph.D., Asst. Research Scientist, Center for Human Development, University of California, San Diego
Adults with autism and their families may be interested to know that the scientific community is turning more attention toward understanding the full life course of autism spectrum disorders (ASDs). While a great deal of research is directed toward understanding the causes of the disorder and developing interventions for young children, we still know relatively little about how the disorder is expressed in adults and how autism changes as individuals on the spectrum get older. This year one of the Invited Educational Symposia at IMFAR was dedicated to this topic, and entitled: Adults with Autism Spectrum Disorders: Challenges for Epidemiological and Outcome Research.
The first two speakers Traolach “Terry” Brugha, M.D., and Fiona Scott, Ph.D. come from the UK where they have recently collaborated on studies of adults with Autism Spectrum Disorder. Dr. Brugha and his colleagues conducted a large epidemiological survey to assess the prevalence of ASD among adults living in the general community (published earlier this month in Archives of General Psychiatry, 2011; v. 68(5): pp. 459-466). The rates of ASD diagnosis have been rising rapidly in the last many years and it is generally accepted that at least part of this increase is due to increased awareness of the disorder among pediatricians, educators, and other child specialists, and to improvements in detection and diagnosis especially in individuals who do not have comorbid intellectual disability. However, it is important to remember that this also implies that there may be a large number of adults who could meet the criteria for an autism diagnosis but who have never been diagnosed with a disorder on the spectrum. To address this, Dr. Brugha and his colleagues contacted adults at more than 13,000 residential addresses in a door-to-door Adult Psychiatric Morbidity Survey in England. Using a stratified random sampling approach, 7,461 individuals participated in first phase interviews which included screening for a variety of psychiatric diagnoses. Individuals who met certain criteria on a 20 item screening questionnaire for autism spectrum disorders were selected to participate in more in-depth assessments including the ADOS (Autism Diagnostic Observation Schedule) and ADI (Autism Diagnostic Inventory). After all testing was completed, 19 individuals were determined to have previously undiagnosed autism spectrum disorders which the authors estimated represents of a rate of 9.8 per 1,000 in the general UK population. Importantly, they did not find evidence of any significant differences in rates across age. That is, it appeared that the oldest individuals were just as likely to have a previously undiagnosed ASD as the youngest.
The next speaker was Dr. Fiona Scott of the University of Cambridge, who is also part of the Adult Psychiatric Morbidity Survey in England. Dr. Scott focused on the particular challenges of accurately diagnosing ASD in higher functioning adults who did not have pre-existing diagnoses. ASD is a developmental disorder and accurate diagnosis requires knowledge of the individual’s social, communicative, and behavioral development during early childhood. The APMS study focused on a higher functioning population that may not have sought services during childhood and particularly wanted to include adults of all ages. Accurate diagnosis is particularly challenging in this population because it is often difficult or impossible to acquire accurate information about the early developmental period. Community-living adults in their 50s, 60s, or 70s may not have living parents who can describe their early development and if they do, these parents are being asked to recall subtle behavioral changes from many decades before. Accurate diagnosis may be further hindered by our limited knowledge of the life course of behaviors. The behaviors and abilities of individuals with ASD change as they get older, as part of normal maturation, as a result of the interventions and training that they partake in, and in response to the challenges that they face in daily life. For example, Dr. Scott pointed out the possibility of comorbid psychiatric disorders such as depression that may arise later in life and may make diagnosis less clear. This could be particularly problematic for previously undiagnosed populations such as those in the APMS study who would not have received outside support for dealing with social challenges.
Other diagnostic challenges include gender differences in ASD. The APMS study found a 9:1 ratio between males and females in the rates of ASD whereas most studies of children find ratios closer to 4:1. This may mean that the screening tools that were used need to be modified for use in women or it may be an artifact of the community-dwelling population that was examined. Women with ASD are often more severely affected cognitively than males and require more behavioral support, but individuals living in institutional housing were excluded from the APMS study.
The only member of the panel who was not from the UK was Marsha Seltzer, Ph.D. of the Waisman Center at the University of Wisconsin. Dr. Seltzer has been following more than 400 children and adults with ASD, and their families, for about 12 years. She is evaluating people who ranged in age between 10 and 52 years when they first entered the study and her research group continues to follow them. Dr. Seltzer reported several interesting findings from their series of studies. On average, individuals in her study showed improvement in social reciprocity and reductions in problematic repetitive behaviors and stereotyped interests across the first 6 years of the study. About 30% also showed significant improvements on the Scales of Independent Behavior-Revised which measure self-care and community living skills as well as cognitive and motor abilities. These improvements could be a result of the supports and interventions that the individuals receive in the community or could simply be the natural life-course of the disorder. However, Dr. Seltzer also reported a study that raises the question of whether even greater improvement might be possible if better support structures were provided. In a study that looked selectively at younger adult subjects who were exiting high school they found that, although repetitive behaviors decreased with time, the rate of improvement was much higher while students were still in school, but slowed substantially (or even regressed) after leaving school.
The final speaker was Patricia Howlin, Ph.D. of King’s College in London who provided a broader perspective of the natural life course of ASD across the life span. She reviewed outcome studies from 1967 to the present. These studies tend to classify individual outcomes as “good”, “fair”, “poor” or similar categories based on the level of independence achieved. For example, those who live in institutions are given poorer ratings than those who live by themselves and those who have part-time jobs rate better than those in sheltered employment or day programs. Over the years there appears to have been a slight decline in rates of “good” outcomes compared to “fair” or “poor” outcomes in such studies, but Dr. Howlin pointed out the subjectivity of these ratings and the difficulty of interpreting the effects of service changes such as the move from housing in large institutions to small group homes. Studies have also found that as much as 16% of adults with ASD develop additional psychiatric diagnoses such as depression and obsessive compulsive disorder which may be triggered by life stressors (citing Hutton et al., 2008). But those with good community support may have better outcomes (citing Farley et al., 2009).
The symposium on Adults with Autism Spectrum Disorders presented some important findings on the topic and also pointed out some of the unique challenges to this area of research. Identifying and recruiting this population is not a trivial task but one which must be addressed. Efforts to improve available tools in this area are moving us forward and it is clear not only from this symposium but from other presentations given at the IMFAR meeting — on diagnostic tools targeted at verbal and non-verbal adults, interventions for adults, and changing health status — that this area of research will continue to grow.
Daniel Lightfoot, Ph.D., Director of the Autism Tissue Program
Ricardo Dolmetsch, Ph.D. has a vision for autism research. Using pluripotent stem cell (iPSC) technology to create rare stem cells from other “common” cells of the human body cells, Dolmetsch and his lab at Stanford study neurodevelopmental disorders such as autism.
Unlike embryonic stem cells or adult stem cells which are isolated from existing and often difficult to obtain tissues, iPSC’s are “created” from easy to obtain and plentiful sources, such as skin or hair samples. This is accomplished through a unique process where cells are developmentally regressed to an earlier state.
To appreciate the concept of a stem cell, consider a seed. As a single cell it holds the potential to grow into an adult plant. It is a “stem cell” – one that can change or develop into any cell of the plant, from a leaf cell, to a flower cell or into a root cell. Through iPSC technology, this process is reversed. Scientists can developmentally regress an adult cell into an earlier cell like a seed. In short, scientists can turn a piece of a leaf into a seed, which could then grow into any cell of the plant. Though this does not at all imply that science can create a whole person from a skin sample, it does, however, allow researchers to easily create a variety of cells that can then be used for scientific study.
Once stem cells are created, they can be induced to develop into brain cells. For the first time, scientists are directly studying living brain cells in the lab. How these cells grow, interact, communicate, organize into groups and what helps or impairs these cells’ growth is now being more effectively studied. Additionally, stem cells have the unique ability to replicate without changing, meaning that from a single skin or hair sample many cells can be created. This allows a near limitless source of resources for scientific inquiry.
Dolmetsch shared this vision at a keynote presentation at IMFAR. He and his colleagues have now created an entire repository of stem cells from individuals with neurodevelopmental disorders. By comparing autism brain cells, with Timothy Syndrome and other disorders, the research team is not only learning about the differences among these conditions, but also the commonalities. Once the brain cell is created, it is possible to experiment with different compounds to determine whether they can restore neuronal function. Thus, stem cells provide a platform for drug screening. A deeper understanding of these disorders will also contribute more generally to a fundamental appreciation of how the human brain works.
Alex Plank of WrongPlanet.net sits down with Peter Bell of Autism Speaks at IMFAR 2011. Peter and Alex have a discussion on a balcony that overlooks the bay. This year’s International Meeting for Autism Research was held in San Diego, the site of the inaugural meeting.
Peter Bell, the Executive Vice President for Programs and Services, reflected in a blog post, ‘Stakeholders Make Their Mark at IMFAR 2011.’