January 7, 2010
Can it really be 2010? It seems like just yesterday that we were celebrating the beginning of the new millennium and worrying that our computers would crash when the year turned 2000. Already a decade has gone by since that time. Looking back over the past 10 years, how much progress have we made in our efforts to improve the lives of people affected by autism and their families? Let's take a look at a few of the scientific discoveries that were published in 2000 and consider how far we have progressed in the past decade.
In 2000, Jacobson and Mulick1 published a controversial cost-benefit analysis examining the long term financial impact of early intervention in autism, boldly suggesting that treating children with autism is a very cost effective investment. Unfortunately, because many still questioned whether early intervention is effective, families continued to shoulder the financial burden of their child's intervention. Now, ten years later, fifteen states have put an end to insurance discrimination and require coverage of autism behavioral health treatments; with national health care reform poised to pass in the coming weeks, we are on the verge of an era when will see the end of insurance discrimination for individuals with autism spectrum disorder (ASD).
Tony Charman2 published a study unveiling a new autism screener called the Checklist for Autism in Toddlers (CHAT) in 2000. Yet, people were skeptical that it was possible to screen for autism in toddlers. By 2007, however, the American Academy of Pediatrics had recommended that all children be screened for autism at their 18- and 24-month checkups using these tools. Today, scientists are exploring ways to identify ASD in the first year of life, before the full syndrome of ASD is present. A study by Sally Ozonoff3 published this year suggests
Sally Ozonoff, Ph.D., Professor of Psychiatry and Behavioral Science, UC Davis MIND Institute
that we might not need high-tech measures; one of the best predictors of ASD is parents expressing concerns about their one-year-old baby, proving once again that we need to listen to parents and take their concerns seriously.
As we make strides in early identification, it's reassuring to know that we also now have effective interventions that are appropriate for children at risk for ASD as young as 12 months of age. This year, my colleagues and I4 reported the results of the first randomized controlled trial of an intensive behavioral intervention for toddlers with ASD. Using an intervention model that combines developmental relationship-focused approaches with ABA teaching strategies, the intervention provided for 2 years resulted in significant increases in IQ, language ability, and adaptive behavior. We were pleased to see this intervention study listed among Healthday's Top Health News for 2009.
Next, let's consider the progress we've made in the area of genetics over the past decade. The author of a Newsweek article on autism published in 2000 noted that "researchers are studying 'hot spots' on several chromosomes that could harbor culpable genes, but none of those regions has been linked consistently to the disorder." Around the same time, Cure Autism Now began investing in a large genetic database (Autism Genetic Resource Exchange – AGRE) and urged scientists to share their genetic data so that discoveries could be made more rapidly. This year, using data from over 2000 families who have generously contributed their DNA to AGRE (now funded by Autism Speaks), the discovery of a specific autism susceptibility gene involved in brain development was heralded by TIME magazine as one of the top 10 medical
breakthroughs of 2009. Hakon Hakonarson, Gerard Schellenberg, and colleagues5 reported that genes that code for proteins called cadherins were associated with risk for ASD. During early brain development, these proteins help neurons find the correct place in the brain and make connections with other neurons. Interestingly, cadherin is expressed in the frontal cortex, an area that is responsible for higher order thinking and complex social behavior, which is known to be affected in autism. Using a different technology that looks for microscopic deletions and duplications in our genome, the same group6 reported that several genes that regulate a biochemical system called ubiquitin are also linked to ASD. Similar to the cadherin genes, the ubiquitin system regulates the formation of connections between neurons.
This same study found that other genes involved in connectivity between neurons – such as neurexin – were also affected by duplications or deletions. A common theme is developing from these findings, namely, that autism is related to genetic alterations which, either on their own or together with environmental factors, disrupt normal connectivity in the brain.
Fortunately, these genetic findings are finally motivating large pharmaceutical companies, for the first time, to seriously invest in autism drug discovery research. This year, for example, Pfizer announced a major investment in autism drug discovery which includes a dedicated autism neuroscience unit. In addition to developing better medications for anxiety, sleep disturbances, and other problems that people with ASD suffer from, a longer term goal is to develop medications target the core biological issue at the center of autism, for example, those that can restore normal connectivity within the brain. As more effective medications become available during the next decade, these very likely will be used in combination with behavioral interventions. After all, the goal of behavioral interventions is also to form new connections in the brain to support the development of social behavior and communication. For many children, behavioral interventions can remediate the problems in brain connectivity. For others, however, the progress is very slow. The hope is that medications that improve brain plasticity and function will help individuals with ASD become more responsive to behavioral interventions. The idea that behavioral and medical interventions are a powerful combination was demonstrated in another important study published this year. Aman and colleagues7 found that, in combination, the use of medication and parent training are more effective for reducing serious behavioral problems in children with ASD than medication alone.
Returning to the year 2000, a controversial study by Horvath8 was published in the New England Journal of Medicine entitled "Secretin treatment for autism." It was claimed that secretin could reverse the symptoms of autism. Parents desperate to try secretin were willing to pay up to $1,000 for a single dose and the supplies of secretin quickly disappeared. Unfortunately, several controlled trials subsequently reported a lack of secretin's effectiveness despite initial enthusiasm. However, Horvarth's article did have the positive effect of raising awareness of gastrointestinal (GI) problems in ASD. Today, the Autism Speaks-funded Autism Treatment Network (ATN)9 is developing evidence-based guidelines for physicians to use to screen, assess, and treat GI conditions in children with ASD, recognizing that these conditions are not only common, but their treatment can greatly improve the quality of life for individuals with ASD and their families. To develop a targeted GI research agenda, in 2009, the ATN spearheaded the largest conference to date that specifically addressed the gastrointestinal issues of children and adolescents with ASD. Over 150 people attended the satellite symposium held in Washington, DC in partnership with the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHAN) and the American Academy of Pediatrics.
The ATN is establishing standards for medical care for autism as it is increasingly recognized that ASD is not solely a condition affecting the brain, but rather one that affects whole body systems, such as the immune system. This year, based on a study supported by Autism Speaks, Paul Ashwood, Judy Van de Water, and colleagues10 reported that children with ASD have decreased levels of a molecule that is involved in immune regulation, called interleukin (IL)-23. Children with lower levels of IL-23 had more severe ASD symptoms. The precise role of IL-23 in ASD is not understood; however, it is thought that too little or too much immune activity during the prenatal period can impair development of neurons. Family history of specific immune conditions may also increase the risk for ASD. In a large study of all children born in Denmark from 1993-2004 (689,196 children), Atladóttir11 and colleagues reported that ASD is associated with a maternal history of autoimmune disease, specifically, rheumatoid arthritis and celiac disease. A family history of type 1 diabetes also increased risk for autism. It is possible that genes that contribute to these autoimmune diseases also contribute to ASD. Research on the role of the immune system in ASD continues to be a high priority for research funding by Autism Speaks.
So, in many respects, we are making real progress. But, for the many individuals with ASD and their families who continue to struggle and suffer each day, progress isn't nearly fast or significant enough. This point is perhaps most clearly driven home by the new prevalence studies published by the CDC this year. Looking back at the 2000 Newsweek article, the author stated, "Autism is now thought to affect one person in 500." In 2007, the CDC reported that ASD affected 1 in 150 children12. This year, the CDC published two studies – one by Michael Kogan and colleagues13 and the second by Catherine Rice and colleagues14 – that reported that ASD now affects roughly 1% of children in the US (1 in 110) and an even higher percentage of boys. That's a whopping 500% increase in prevalence over the past decade! Increased ASD awareness and access to diagnostic services surely account for a significant proportion of the increase, and this is indeed a sign of progress. However, epidemiological studies published this past year15 (and currently in press), including the most recent CDC study, indicate that some of the increase in prevalence remains unexplained, and this is a cause for concern.
A careful look at the 2007 and 2009 CDC reports provides some interesting insights. These reports are based on samples collected four years apart, 2002 versus 2006, respectively. One reasonable explanation for the increase seen over this four year period is that ASD is now being diagnosed at an earlier age. However, the average age of diagnosis only decreased by 5 months over this period, hardly a large enough difference to account for the 57% increase. Another possibility is that clinicians are now diagnosing more children on the milder end of the autism spectrum, including children with higher cognitive ability. However, the CDC investigators found that there was no change over the four year period in the proportion of children with the broader ASD diagnosis (i.e. PDDNOS) versus classic autism. And although there were more children with higher cognitive ability in the 2009 sample, the percentage of such children was only slightly different (59% compared to 54%). To quote the authors of the 2009 CDC paper, "although improved ascertainment accounts for some of the increase, a true increase in the risk for ASD cannot be ruled out."
There is an urgent need to understand what factors could be accounting for a true increase in prevalence. Dr. Tom Insel, Director of the National Institute of Mental Health and Chair of the Interagency Autism Coordinating Committee, agrees. In a recent interview, Dr. Insel stated, "As far as I can tell, the burden of proof is upon anybody who feels that there is not a real increase here in the number of kids affected." He went on to say, "you really have to take this increase very seriously – from everything they are looking at, this is not something that can be explained away by methodology, by diagnosis." Later, he added, "There is no question that there has to be an environmental component here."
Families don't want to wait another decade for answers. Autism Speaks launched a major initiative to study environmental factors well over a year ago, but this is just a start. We need large data sets that provide detailed environmental, demographic, and genetic data to find answers. One thing we have learned in the past decade is that there won't be one cause for the increase, but rather multiple causes that contribute to different forms of ASD. Some types of ASD will be largely genetically determined, but we know that many forms of ASD will involve environmental risk factors. Genetic research will help guide our search for environmental risk factors, and vice versa. The relatively new field of epigenetics, which explores how the environment influences the expression of risk genes, will almost certainly be important for finding answers. The hope is that this line of research will lead to avenues for prevention and new approaches to treatment.
In addition to the alarming statistics on prevalence, the 2009 CDC study headed by Rice contained some additional interesting information. Did you notice the statistics above indicate that close to 60% of children with ASD have IQs above 70 by age 8? This is a very different picture of autism than is often portrayed. We can hope that part of this change is due to earlier diagnosis coupled earlier and more effective intervention. Another study published this year also shatters some myths about autism. It was previously thought that children with ASD who develop language do so by the age of 5. However, in a study published this year, Pickett16 documented 167 cases of individuals with ASD who developed speech between 5 and 12 years of age. These results are good news for many parents whose young children have yet to speak.
Hope for the future will depend on continued autism research funding. In 2008, in the US, over $222 million was spent on autism research, with 35% of those funds coming from private foundations, such as Autism Speaks17. That amounts to $78 million from private sources. That's pretty impressive. While Autism Speaks and the NIH are investing in research aimed at discovering the causes and effective treatments for ASD, real and rapid progress will require a substantial investment in autism research by the federal government. In a compelling 2009 article, Joachim Hallmayer and colleagues18 chronicled the trends in US autism research funding over the past decade, noting that funding for NIH autism research increased fivefold since 1997, from $22 million to $108 million in 2006. Hallmayer noted the key role of Autism Speaks, and its legacy organizations the National Alliance for Autism Research and Cure Autism Now, in raising and leveraging research dollars and changing the landscape of research priorities in the US. In Hallmayer's words, "the landscape of autism research is changing because of the involvement of the private sector, placing advocates at the table of research priority decision-making."
Three events of 2009 offered additional glimmers of hope for achieving the kind of federal research funding we need. First, using funds gained through the American Recovery and Reinvestment Act designed to stimulate the U.S. economy, the NIH invested an additional $89 million in ASD research on top of their regular autism research spending. Some of these funds were designed to address the gaps in our knowledge identified by the federal government's first strategic plan for ASD research, also published in 2009. This infusion of funds only covers two years of research, however, and is hardly enough to make the kind of progress that is needed.
Second, during his presidential campaign, then Senator Barack Obama acknowledged that the urgency and scale of the ASD public health crisis required an investment of at least $1 billion annually in ASD research and treatment, listing autism among the top three health priorities of the U.S., along with heart disease and cancer. This may seem like a lot of money, but it pales in comparison to the $35 billion spent on caring for persons with ASD in the US each year. We need to work together to make sure this pledge is kept.
Third, in an address at the Meeting of the Society for Neuroscience last fall, the new director of the National Institutes of Health, Francis Collins, highlighted autism, noting that autism is "a disease of great public concern and great scientific puzzlement." So, 2010 holds promise for an increased commitment by the federal government, but the fulfillment of that promise depends on the ASD community having one strong voice. This is challenging because the autism community is full of passion and a great diversity of needs and perspectives.
Every day, I have the privilege of hearing from the variety of voices that make up the autism community. My hope for 2010 is that we can join together to fight for the unified cause of reducing suffering for all persons with ASD. We need to fight for the answers that the autism community deserves in the hope that those answers will result in real and rapid progress toward improving the lives of all individuals with ASD.
Very best wishes for the New Year,
Chief Science Officer