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.’
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Serena Hua, undergraduate at UCSD studying Neuroscience and Psychology, founder and president of Awareness and Action for Autism
My purpose in attending the IMFAR Community Conference was anything but to solely learn about the latest research on autism. That is not to say, however, that I was not guilty of clinging to the edge of my seat desperately absorbing all the mind blowing information that was being presented to me and the sea of at least 200 or so parents, doctors, researchers and teachers. Captivated I was, despite being an undergraduate here at UCSD where these kinds of exciting research surround you each and every day, I didn’t see the conference as the sole opportunity for me to dive into all that was going on in the science hemisphere of the ASD world. I was here for other reasons.
The crowd of attendees, consisting of mostly parents and professionals that work with individuals on the spectrum were, on the other hand, all here for the research and the new knowledge. I couldn’t help but notice how enthralled they were to be there, to meet other parents and, most importantly, to learn about how dedicated individuals like themselves were playing their own part in this battle against autism. They sat hour after hour, listened to talk after talk, bombarded the speakers with questions one after the other – a feat us college kids won’t even dream of accomplishing. They made every minute of this conference worth their time, ensuring that their questions were answered or at least acknowledged with a ‘good question!’ kind of response. Sitting there next to a grandparent of an ASD kid and cracking up over the diverse panel of absolutely brilliant young adults with Asperger’s, or “Aspies” as they call themselves, I found myself savoring every second of the conference.
What I remember most from the day was when Stephen Shore and John Elder Robison spoke during one of the breakout sessions about their experiences as individuals with ASD. As they were sharing their quirks and insights on the disorder, I turned to look at everyone around me, and smiled to myself. I couldn’t pinpoint why, but at that moment, I was so happy to be where I was. To me, these were people who stood for the hope that someday my own six-year-old cousin could have his own family, lead his own life, and stand for what he believed in. I felt like I wanted to shout that to the world, and I wondered if those around me were feeling the same way.
Last year, I started the Awareness and Action for Autism organization, which aims to find opportunities for college students to help out in the ASD community. My organization stemmed from the feeling of helplessness when it came to helping my autistic cousin; away from home, I could not do anything significant to support him and his family at a time when they needed support the most – and that killed me. This was my effort to do my part. Starting this club was my effort to inform those who didn’t know a thing about autism – raising awareness. I also wanted to channel other students’ desires to help into producing practical outcomes, like our Peer Mentoring Program and Journal Clubs, with goals to ultimately benefit those with ASD – that is the action part. If I couldn’t directly help my cousin, the least I could do was to try to help others.
In the end, the real reason I attended the conference was the opportunity to be in that sea of 200 passionate family members and advocates – psychologists and teachers and grandparents and the ASD people themselves. The IMFAR Community Conference was, for me, a chance to be around those who understood and cared about everything autism; it was an chance for me to be recharged and re-inspired to continue doing what I had set out on doing all along: to play my part in the ASD community.
The author is a guest blogger, Ashley Scott-Van Zeeland, Ph.D. and she is a Dickenson Fellow at the Scripps Translational Science Institute in La Jolla.
This was the second year IMFAR hosted an Invited Educational Symposium on Imaging Genetics in autism spectrum disorders. Dr. Susan Bookheimer, a leader in brain imaging and one of the pioneers of imaging genetics, and Dr. Daniel Geschwind a world-renowned autism geneticist, chaired the session. The goals of the symposium were to introduce the principles behind imaging genetics and demonstrate methods by which various researchers are using imaging genetics to discover relationships between genetics and brain function.
The first speaker was Dr. Susan Bookheimer, Professor of Cognitive Neurosciences from UCLA. Dr. Bookheimer gave a broad overview of the use of brain images as quantitative measures for use in imaging genetics investigations. Essentially, neural measurements such as activation or metabolic response, structural volumes, or connectivity measures can be thought of as being one step closer to the mechanism of gene action than broad diagnostic classifications. Therefore, these types of ‘endophenotypes’ are more strongly associated with gene variants and should considerably increase the ability to identify brain-gene relationships.
Dr. Daniel Geschwind, Chair of Human Genetics and Professor of Neurology at UCLA followed with a general primer on genetics to introduce all clinicians, brain imagers, and non-geneticists to the types of genetic assays available. The goal of Dr. Geschwind’s talk was to encourage non-geneticists to consider what is “reasonable” from a genetics perspective when designing studies. He highlighted three main frameworks for imaging genetics studies: 1) Identify genetic factors that underlie normal brain structural and/or functional variation 2) use differences in brain imaging measures to identify disease-associated genes, or 3) use brain imaging as a way understand the neurobiological effects and neural mechanisms of disease-associated genes. He also re-emphasized the issue of statistical power in the search for disease-associated genes, which depends on many factors but can be increased by using brain imaging that likely has larger detectable gene effects than broader phenotypes such as autism diagnosis. He also stressed that the best imaging genetic approaches are hypothesis driven, with known implicated brain regions or neural effects to limit statistical issues caused by testing many genetic markers over many brain regions.
After the introductory talks by Drs. Bookheimer and Geschwind, there were three more talks that went into greater detail about current applications of imaging genetic approaches in the study of autism – the first being by Dr. Joshua Trachtenberg, Assistant Professor of Neurobiology at UCLA. Dr. Trachtenberg presented methods for imaging dendritic growth in animal models. Using cutting edge 2-photon microscopy techniques, Dr. Trachtenberg is able to examine the neurobiological effects of candidate autism risk genes in a living animal. His lab has been working on the PTEN gene, which has been associated with an enlarged brain. In order to determine how PTEN contributes to an enlarged brain, Dr. Trachtenberg is able to selectively alter the PTEN gene in mouse brain after birth and monitor the changes in neural architecture over time. In the PTEN mutant animals, Dr. Trachtenberg observed up to 50% extra growth of dendrites – neuronal structures that receive input from other cells – suggesting a mechanism by which this autism-associated gene contributes to larger brain size. Importantly, he also presented evidence that the dendrites involved in long-range communication circuits are more affected than those involved in short-range circuits – a story that is emerging as a consistent finding across many measures of brain connectivity in autism.
Next, Dr. Declan Murphy, Professor of Psychiatry and Brain Maturation and the Head of Department of Forensic and Neurodevelopmental Science at Kings College in London presented an overview of the state of the field for serotonin genes and imaging genetics. Serotonin is a neurotransmitter involved in both brain function and brain development, and has been associated with behaviors such as aggression, affiliative behaviors, and obsessional behaviors. There are two major serotonin genes that have been the focus of imaging genetics studies – MAOA and 5-HTTLPR. MAOA is involved in the breakdown of serotonin and 5-HTTLPR encodes a protein that transports serotonin into neurons. Both genes have been associated with many neuropsychiatric disorders, including autism. Dr. Murphy presented studies in which activity in the amygdala and fusiform gyrus, regions thought to play a role in autism, was associated with different versions of 5-HTTLPR. However, he noted that although there is some evidence for serotonin dysfunction in autism, the evidence is not conclusive and imaging studies reflect this as well. In structural MRI studies, investigators have found frontal lobe abnormalities associated with the serotonin transporter, though this has not consistently been replicated. Within this talk, Dr. Murphy emphasized that it remains important to search beyond simple gene effects and consider systems-based approaches, developmental effects, gene-gene interactions and pharmacogenetic effects in imaging genetics studies.
I had the great pleasure of wrapping up the session by describing a general framework for pursuing targeted imaging genetics studies in autism, using a recent study that explored frontal lobe connectivity and an autism risk gene, CNTNAP2. As imaging genetics studies can be quite difficult, it is important to begin with well-devised experimental paradigms and testable hypotheses for gene effects. Since CNTNAP2 encodes a protein that is involved in cell-cell interactions and synaptic transmission, we reasoned that CNTNAP2 might be related to neural connectivity. As mentioned by Dr. Bookheimer in the introduction, it is important to use brain imaging as a quantitative measure of brain function or structure. To this end we chose to use a functional paradigm that we knew would elicit activity in regions where CNTNAP2 is expressed during development. We observed differences in frontal lobe activity in both typical children and those with autism depending on which CNTNAP2 allele they carried, and also found differences in connectivity patterns with the frontal lobe such that children who carried the autism-associated risk gene had more local frontal connections and reduced long-range connections. In sum, by leveraging information about the role of CNTNAP2 in the brain , we were able to better understand the mechanism by which CNTNAP2 contributes to increased risk for autism using an imaging genetics approach.
Overall, the application of imaging genetics to autism spectrum disorders is beginning to reveal very interesting neurobiology and I expect we will see more of these types of studies at IMFAR 2012!
Autism Speaks Science Board member John Elder Robison is the author of Look Me in the Eye: My Life with Asperger’s and Be Different: Adventured of a Free-Range Aspergian. You find out more about his IMFAR experience, here, here, and here.
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To find out more about ‘Innovative Technology for Autism’ visit here.
This is a guest post by Peter Bell, the executive vice president for programs and services at Autism Speaks. He oversees the foundation’s government relations and family services activities and also serves as an advisor to the science division.
The International Meeting for Autism Research (IMFAR) celebrated its 10th anniversary this year. To commemorate this special occasion, the organizers returned to San Diego the site of the inaugural meeting in 2001. Although the city pretty much looks the same (one notable exception is the new Petco Park baseball stadium downtown), the landscape of IMFAR has undergone radical changes. While IMFAR is first and foremost a scientific meeting, the meeting has developed into a healthy blend of science and stakeholder perspectives.
The most notable difference between IMFAR 2001 and IMFAR 2011 is attendance. This year’s meeting attracted almost 2000 participants compared to just 250 when IMFAR began. The original meeting was a satellite to the very large Society for Neuroscience conference. Now IMFAR spawns its own satellite meetings. More than 1,100 research abstracts were presented this year over the course of three days. Ten years ago, there were fewer than 200 abstracts and the meeting lasted just a day and a half. Without question, the quality of research has undergone major transformation during the past decade.
The idea to create IMFAR was first conceived and supported by the stakeholder community. In fact, the first several years of IMFAR were organized by CAN and NAAR, which later merged with Autism Speaks, with strong support and guidance from the MIND Institute at UC Davis. Eventually, the International Society for Autism Research (INSAR) was formed to give autism scientists and students a membership organization to host the meeting and further develop the field. INSAR is now responsible for producing IMFAR each year while Autism Speaks and several other advocacy organizations continue to play a critical role and provide financial support in the form of sponsorships.
Two years ago, INSAR President David Amaral formed a Community Advisory Committee to ensure the stakeholder community is well represented and positively contributes to the success of the Society and its annual meeting. The Committee is chaired by Peter Bell from Autism Speaks (also a parent advocate) and co-chaired by self-advocate John Elder Robison, author of “Look Me in the Eye” and “Be Different”. Total membership includes six parent advocates, two self-advocates and one graduate student.
This year’s IMFAR meeting included many activities geared toward the stakeholder community. For the second consecutive year, one of the local academic institutions (University of California, San Diego) hosted an IMFAR Community Conference the day before IMFAR started. Over 300 attendees including parents, educators, therapists, clinicians and students attended this year’s event. One of the highlights of the conference was a panel of teens with autism who talked about their experiences living on the spectrum.
Once IMFAR opened on Thursday, the spotlight focused on several advocates who were honored at the Awards Reception. In addition to awarding Dr. Margaret Baumen from MassGeneral Hospital with the Lifetime Achievement Award, the INSAR board of directors created a new annual award called the INSAR Advocate Award for the important contributions that advocates make to research. Appropriately, the inaugural award was given to the founders of the organizations that started IMFAR ten years ago, Portia Iversen and Jonathan Shestack from Cure Autism Now (CAN) and Karen and Eric London from the National Alliance for Autism Research (NAAR).
The INSAR board also gave a Special Recognition Award (posthumously) to Bernard Rimland, PhD who is widely recognized for his discovery of the powerful evidence that autism is a biologic disorder and not due to poor parenting. Dr. Rimland later formed the National Society for Autistic Children, which is now known as the Autism Society of America, as well as the Autism Research Institute. This honor was especially fitting because San Diego was his home. His wife Gloria and son Mark were on hand to accept the award and enjoyed a standing ovation in memory of Dr. Rimland’s significant contributions to autism research.
A special surprise greeted those who attended the annual reception at the conclusion of day one. Under beautiful sunny skies on the rooftop deck of the Manchester Hyatt Hotel, IMFAR attendees were treated to a wonderfully entertaining performance by some of the stars from “Autism: The Musical”, the Emmy-winning HBO documentary. Not surprisingly, autism researchers know how to have a good time thanks to the musical talents and personalities presented by these teens.
On Friday, the annual Stakeholder Networking Luncheon, sponsored by Autism Speaks, was held to encourage greater interaction between the autism researchers and members of the stakeholder community. This year’s event attracted over 90 participants, up from about 60 the year prior. Most of the attendees were parents or grandparents, with about a dozen participants being autistic individuals and another dozen being siblings of a person with autism.
The luncheon included presentations by both scientists (INSAR President David Amaral from UC Davis, IMFAR Keynote Speaker Ricardo Dolmetsch from Stanford University and ATN Clinical Coordinating Center Director James Perrin from MassGeneral Hospital) as well as stakeholders (parent/researcher Sarah Logan from Medical University of South Carolina and autistic self-advocate/author John Elder Robison). Stay tuned for video highlights of the luncheon by Alex Plank and his crew from Wrong Planet.
During her brief remarks at the end of the luncheon, Sarah Logan, who is a PhD student at Medical University of South Carolina as well as the mother of a 14 year old boy with autism, referenced a quote from Albert Einstein: “A man should look for what is, and not for what he thinks should be.” She eloquently pointed out that as stakeholders, it’s natural (and easy) to become emotionally invested. Yet IMFAR presents science as science – with passionately curious individuals who can find harmony between the emotionally invested and the empirically driven.
Sarah further explained: “At the end of the day, one thing we all have in common is that we want a better quality of life for our loved ones living with autism. And that comes with knowledge. Knowledge is power. IMFAR is an amazing place to both gain, and share knowledge that will lead to improved quality of lives for all of those involved – parent, individuals, caregivers, families and siblings.”