In honor of the anniversary of Autism Speaks’ founding on Feb 25, for the next 25 days we will be sharing stories about the many significant scientific advances that have occurred during our first five years together. Our 25th item, Autism Prevalence Reaches 1:110, is from Autism Speaks’ Top 10 Autism Research Events of 2009.
In 2009, two major studies using different research methodologies yielded strikingly similar and eye-opening results showing that ASD affects approximately 1% of children in the United States. Based on data collected just four years earlier, it was found that ASD affected 1 out of every 150 children in the U.S. This represents a 57% increase in ASD prevalence in a relatively short period of time. Both studies also found that ASD continues to be four times more common in boys than girls.
In the first study, published in Pediatrics, authors from the U.S. Department of Health and Human Services (HHS) and the Centers for Disease Control and Prevention (CDC) collected data through the National Survey of Children’s Health (NSCH) on parent-reported diagnosis of ASD. Among a nationally representative sample of 78,000 children aged 3 to 17 years, the investigators found that 1 in 91, or an estimated 673,000 children in the U.S. had an ASD. While concerns lingered over the parent-reported nature of the data, this large-scale study set the stage for another major publication on ASD prevalence with similar results.
In December researchers at the CDC released new prevalence data collected by the Autism and Developmental Disabilities Monitoring Network (ADDM), a series of surveillance sites throughout the U.S. that maintain medical and service records on children with autism. By abstracting data and subjecting those records to stringent clinical evaluation, the authors found that approximately 1 in 110 children, 1 in 70 boys, met the criteria for ASD. This 1 in 110 statistic, based on data collected in 2006, represents a 57% increase from the 1 in 150 statistic which was based on data collected by the ADDM network in 2002 using identical research methods to the current study.
In a year that was jam-packed with publications on autism epidemiology, a number of other studies sought to investigate the reasons for the dramatic increase witnessed in autism prevalence. Researchers from Columbia University reported that approximately 25% of the rise in autism caseload in California between 1992 and 2005 could be directly attributed to changes in diagnostic criteria that resulted in a shift from mental retardation diagnosis to autism diagnosis. Therefore, converging evidence from this study and others around the world suggests that while changes in diagnostic practice may account for a portion of the increase, they cannot alone explain the rise in autism prevalence, and other factors, including environmental factors, likely play a role. One environmental factor that continues to be implicated in the increase in autism prevalence is parental age. Researchers from the California Department of Public Health reported in 2009 that parental age and particularly maternal age is a significant risk factor for autism, with a 10-year increase in maternal age increasing the odds of having a child with autism by 38% and mothers over the age of 40 at highest risk.
The prevalence studies of 2009 helped shed additional light on the immense nature of the autism public health crisis. With 1% of the U.S. population affected by ASD, and emerging data suggesting that 1% of the global population may be affected by ASD, never has the need for funding to support research into the causes and treatments of ASD been greater. In addition, these findings call attention to the necessity for more accessible diagnostic and intervention services for the growing population of those affected. In the CDC’s ADDM report and a separate study published in the Journal of the American Academy of Child and Adolescent Psychiatry, it was reported that while we can now reliably diagnosis autism spectrum disorders at two years of age, children on average are still being diagnosed at close to 6 years of age. This means that there is a large gap between the time that children can effectively be diagnosed at age 2, and the time they are actually receiving a diagnosis – valuable time lost where early intervention services can dramatically improve outcomes.
Did you know?: Autism Speaks, in partnership with the CDC, developed the International Autism Epidemiology Network, a forum to facilitate collaboration and information sharing between autism experts around the globe. Launched at the International Meeting for Autism Research (IMFAR) in May of 2005, today the network supports over 100 participants from 30 countries and its activities have resulted in over $2.5 million in targeted international epidemiology research funding from Autism Speaks. This includes the launch of two RFAs in 2008 designed specifically to better understand global autism prevalence and risk factors – click here for more information on the funded grants.
5|25: Celebrating Five Years of Autism Science Day 24: Early Intervention for Toddlers with Autism Spectrum Disorders
In honor of the anniversary of Autism Speaks’ founding on Feb 25, for the next 25 days we will be sharing stories about the many significant scientific advances that have occurred during our first five years together. Our 24th item, Early Intervention for Toddlers with Autism Spectrum Disorders, is from Autism Speaks’ Top 10 Autism Research Events of 2009.
Although previous studies have found that early intervention can be helpful for preschool-aged children, interventions for children who are toddlers are just now being tested. As 2009 came to a close, the results were unveiled for the first controlled study of an intensive early intervention appropriate for children with ASD who are less than 2½ years of age. Published in Pediatrics, results of this study showed that a novel early intervention program was effective for improving IQ, language ability, and adaptive behavior in children as young as 18 months.
The intervention, called the Early Start Denver Model, combines applied behavioral analysis (ABA) teaching methods with developmental ‘relationship-based’ approaches, thereby blending the rigor of ABA with play-based routines that focus on building a relationship with the child. Children in the study were separated into two groups, one that received 20 hours a week of the intervention – two two-hour sessions five days a week – from University of Washington specialists. They also received five hours a week of parent-delivered therapy. Children in the second group were referred to community-based programs for therapy. Researchers closely monitored the progress of both groups.
At the beginning of the study there was no difference in functioning between the two groups. At the conclusion of the study, the IQs of the children in the intervention group had improved by an average of close to 18 points, compared to only 7 points in the comparison group. The intervention group also had a nearly 19-point improvement in receptive language (listening and understanding) compared to approximately 10 points in the control group. Whereas only one child in the community-based intervention group had an improved diagnosis, seven of the children in the intervention group had enough improvement in overall skills to warrant a change in diagnosis from autism to the milder condition known as ‘pervasive developmental disorder not otherwise specified.’
While the youngest children in the study were 18 months old, this particular intervention is designed to be appropriate for children with ASD as young as 12 months of age. Given that the American Academy of Pediatrics recommends that all 18- and 24- month-old children be screened for ASD, it is crucial that we are able to offer parents effective therapies for children within this age range. This new study strongly affirms the positive outcomes of early intervention and the need for the earliest possible start.
Did you know?: To encourage research in early intervention, at the end of 2006 Autism Speaks funded a set of multi-site randomized trials to investigate the efficacy of different early intervention techniques in toddlers who show early signs of autism. From this effort a Toddler Treatment Network (TTN) was born to establish the groundwork for collaborative studies that can incorporate different aspects of these various intervention approaches. The TTN investigators have also been collecting and sharing information on a variety of best practices, including how to build partnerships with local communities. Importantly, all studies are testing interventions that can be implemented outside the clinic, with the aim of decreasing the time between parent’s first concern and initiation of treatment.
5|25: Celebrating Five Years of Autism Science Day 23: Gastroenterology consensus recommendations provide recognition of the need for specialized approaches to GI problems in children with autism
In honor of the anniversary of Autism Speaks’ founding on Feb 25, for the next 25 days we will be sharing stories about the many significant scientific advances that have occurred during our first five years together. Our 23rd item, Gastroenterology consensus recommendations provide recognition of the need for specialized approaches to GI problems in children with autism, is adapted from a 2009 press release.
Gastrointestinal (GI) problems are a commonly expressed concern of parents of children with autism spectrum disorders (ASD), but families have often found it difficult to find appropriate care for these issues. In December 2009, a consensus statement and recommendations for the evaluation, diagnosis, and treatment of gastrointestinal disorders in children with ASD were published in Pediatrics. These recommendations are an important step in advancing physician awareness of the unique challenges in the medical management of children with autism and will be a prelude towards the development of evidence-based guidelines that will standardize care for all children with ASD. The reports highlighted the crucial need for information to guide care, and emphasized the critical importance of fostering more research in this area, including genetic research, to support the development of these guidelines.
“The Pediatrics paper represents long-sought recognition by the mainstream medical community that treatment of GI problems in children with autism requires specific and specialized approaches,” reacted Dr. Dawson. “Autism Speaks has been actively engaged in the study of GI problems associated with children with autism, working toward enhanced medical community awareness for over five years through its research agenda and the Autism Speaks’ Autism Treatment Network (ATN). Dan Coury, M.D., ATN medical director, commented, “We are delighted to see the publication of important information that can support clinicians and caregivers in providing better care for children with autism, particularly with GI concerns, as parents unfortunately very often find it difficult to identify physicians who have an understanding of these issues and are able to provide appropriate medical care for their children. GI and pediatric specialists from six of the ATN sites participated in the forum and in the development of these recommendations, which shows the power of interaction among the communities and individuals dedicated to this problem. Autism Speaks is already engaged in the crucial next step which is to move beyond these consensus-based recommendations to develop evidence-based clinical guidelines.” In addition to development of evidence-based clinical guidelines for GI issues, the ATN is also currently working on evidence based clinical guidelines for medical management of sleep, and neurologic disorders associated with autism. “Delivery of evidence-based clinical guidelines will serve as excellent opportunities for future training and education of physicians,” added Dr. Dawson.
The consensus statement highlights several important themes, the first emphasizing that GI problems are a genuine concern in the ASD population and that these disorders exacerbate or contribute to problem behaviors. The need for awareness of how GI problems manifest in children with autism and the potential for accompanying nutritional complications and impaired quality of life were also emphasized.
In the second paper, the authors make consensus recommendations providing guidance on how current general pediatric standards of care that can and should be applied for children with ASD. George Fuchs, M.D., a co-author on the two papers and chair of the ATN GI Committee remarked, “The recommendations provide important guidance for the clinician to adapt the current practices of care (for abdominal pain, chronic constipation and gastroesophageal reflux) for the child with autism. The recommendations from the Autism Forum meeting complement the ATN’s on-going work to develop evidence-based, ASD-specific guidelines. The ATN is currently piloting newly created guidelines and monitoring their effectiveness. We anticipate this data will contribute to an evidence-based foundation to support best practices for GI problems in ASD.”
Autism Speaks is committed to the sustained support of efforts that address co-morbid medical conditions in the ASD population. In recognizing that there’s not enough evidence in any GI area and more research is needed, the Pediatric papers reaffirm the importance of the recent November 2009, Autism Speaks sponsored symposium and workshop on Gastrointestinal Disorders in Autism Spectrum Disorders. The symposium and workshop represented an important partnership with the American Academy of Pediatrics, and the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN) – the largest professional society for GI and nutritional specialists, and a professional authority for the development and implementation of pediatric GI guidelines. The symposium raised awareness and provided the latest scientific information to an audience of 168 researchers, clinicians, and pediatric GI and nutrition specialists, most of whom had limited expertise in autism. The symposium was followed by a workshop that brought together a diverse group of experts in GI, nutrition, pediatrics, pain, ASD, and biological research. Recommendations were developed for an expanded and targeted research agenda for the field that will address current gaps in the knowledge base and aim to advance evaluation and treatment of ASD-GI disorders. Proceedings from the meeting are scheduled to be published in 2010. A unique and important element in both the Symposium and Workshop was the inclusion of parents of children with ASD.
Did you know?: Autism Speaks’ Autism Treatment Network (ATN) is developing evidence-based guidelines that will provide specific guidance to physicians on how to address a number of medical issues of concern for children with ASD. The ATN is currently piloting a GI guideline algorithm (decision flow charts) for the assessment and treatment of constipation, and a sleep guideline algorithm for insomnia. The ATN is also working on guidelines in the areas of psychopharmacology and neurology. For more information on ATN guideline activities, please see www.autismspeaks.org/airp.
5|25: Celebrating Five Years of Autism Science Day 22: Combined Therapies Hold Promise for More Effective Treatments
In honor of the anniversary of Autism Speaks’ founding on Feb 25, for the next 25 days we will be sharing stories about the many significant scientific advances that have occurred during our first five years together. Our 22nd item, Combined Therapies Hold Promise for More Effective Treatments, is from Autism Speaks’ Top 10 Autism Research Events of 2009..
Just over three years ago the FDA’s landmark approval of risperidone for the treatment of ASD represented a significant breakthrough for the autism community. Since then other large-scale autism studies have sought FDA approval for drugs that target core or associated symptoms for autism, but unfortunately few of these trials have proven successful. In 2009, taking a cue from other disorders such as ADHD where a combined effect of both medication and behavioral therapies has proven fruitful, researchers published the first successful combined randomized controlled trial for ASD. The paper in the Journal of the American Academy of Child and Adolescent Psychiatry demonstrated that combined pharmacological and behavioral treatments was more effective than pharmacological treatment alone for reducing challenging behaviors.
Risperidone is approved for reducing aggression and irritability in children and adolescents with autism. However, its use still presents a number of challenges to clinicians. Like other atypical anti-psychotics it can have adverse side effects including weight gain, potentially leading to increased risk for obesity, and GI symptoms such as diarrhea and constipation, which can already be problematic for children with ASD. Clinicians must therefore balance the benefit of treating the problem behaviors with the potential for creating new health challenges for the child. On the other hand, behavioral therapies have been shown to be one of the most reliably effective treatments for improving problem behaviors with limited side effects. Combination therapies create a synergistic therapeutic environment in which medication allows a child to get more from behavioral therapies and, at the same time, the benefits of behavioral therapy may mean lower doses of medication are required.
A new multi-site study by the Research Units on Pediatric Psychopharmacology Autism Network, the same group that conducted the pivotal studies leading to the approval of risperidone, investigated whether combining risperidone treatments with a simultaneous behavioral intervention would be more effective than medication alone. Their 24-week study of 124 children ages 4-13, compared a treatment regime of risperidone alone with a combined treatment regimen of risperidone and a parent training program that followed the principles of applied behavioral analysis. While both the combined and medication-only treatments reduced the severity of non-compliant behaviors, the combined therapy resulted in a significantly greater reduction while using lower doses of risperidone. The combined therapy was also better at reducing other challenging behaviors, such as irritability and hyperactivity.
This study provides hope for a wider range of available treatments and greater flexibility for clinicians who should be encouraged to use combined approaches in cases where medications or behavioral interventions are not effective on their own. Confirming the effectiveness of coordinated treatments that take full advantage of the benefits of both pharmaceutical and behavioral approaches also demonstrates the continued need to support research establishing the most effective treatments in all realms. Finally, the vast majority of clinical trials conducted to date have only addressed how an individual treatment compares to a placebo. Very few studies have been conducted that make head-to-head comparisons of two or more treatments as was done here, so the success of this trial will also serve to highlight the utility of “comparative effectiveness trials” for determining the best treatments for ASD.
Did you know?: Autism Speaks’ funded Interactive Autism Network (IAN) is a web-based family registry and social network that brings together thousands of families with autism research and provides a forum for families to report information about their experiences. In a recent study on over 5000 children in IAN, 35% of parents reported that their children were taking at least one psychotropic medicine and the use of these drugs increased with age. The incidence of a comorbid condition such as seizures, ADHD or anxiety increased the likelihood of medication use. The IAN authors also reported on correlations between insurance access and use of multiple medications, noting that those children using public insurance plans (such as Medicaid) tended to be on more medications, possibly due to an inability to get coverage for behavioral therapies.
5|25: Celebrating Five Years of Autism Science Day 21: Toddlers with autism are drawn to movements that are highly synchronized
In honor of the anniversary of Autism Speaks’ founding on Feb 25, for the next 25 days we will be sharing stories about the many significant scientific advances that have occurred during our first five years together. Our 21st item, Toddlers with autism are drawn to movements that are highly synchronized, was originally reported in our Science In the News in 2009.
In its March 29, 2009 issue, the prestigious journal Nature reported on an autism study that focuses on the toddler response to biological motion. Researchers from Yale University found that young toddlers with autism are not sensitive to biological motion, or all movements made by people including facial expressions, speech and gestures. The study, funded in part by Autism Speaks, helps explain why young toddlers with autism often do not make eye contact or pay attention to what others are doing. Instead, toddlers with autism are drawn to movements that are highly synchronized, which is not characteristic of most human movements.
“Since infants as young as two days old are sensitive and pay attention to biological motion,” said Dr. Geri Dawson, chief science officer for Autism Speaks, “these findings could potentially be useful in detecting infants at risk for autism very early in life. It is important to use therapeutic strategies for children with autism that help draw their attention to people, including their facial expressions, and gestures.”
By providing very early intervention, doctors and therapists may be able to influence the trajectory of brain and behavioral development in children with autism so that a more typical development occurs and symptoms of autism are reduced.
Read an NIH press release on the study.
Did you know?: Another Autism Speaks-funded study published in 2009 discovered unusual sensory-motor features of children with autism. Researchers from the Kennedy Krieger Institute and Johns Hopkins University School of Medicine examined motor patterns in children with autism. The findings, published in Nature Neuroscience, suggest that children with autism appear to learn new motor actions differently than do typically developing children. To learn new patterns of movement, children with autism relied much more on their own internal sense of body position (proprioception) rather than visual information coming from the external world. Furthermore, researchers found that the greater the reliance on proprioception, the greater the child’s impairment in social skills, motor skills and imitation.
5|25: Celebrating Five Years of Autism Science Day 19: First Successful Autism Genome-Wide Association Study Results
In honor of the anniversary of Autism Speaks’ founding on Feb 25, for the next 25 days we will be sharing stories about the many significant scientific advances that have occurred during our first five years together. Our 19th item, First Successful Autism Genome-Wide Association Study Results, is from Autism Speaks’ Top 10 Autism Research Events of 2009.
Advances in technology and analytical methods over the past several years have enabled a better understanding of genetic risk factors for ASD. The human genome has over 6 billion DNA nucleotides. Until recently, it has been extremely difficult for scientists to compare two groups of individuals – one affected by a condition versus a comparison group – in terms of their detailed DNA because such comparisons require the analysis of at least half a million to a million individual locations in the genome of thousands of people. New methods, called Genome-Wide Association Studies (GWAS), have now made it possible to perform such comparisons and identify single changes in DNA nucleotides as specific genetic risk factors. Although this powerful technology has already produced exciting findings in other complex diseases, it wasn’t until 2009 that GWAS studies finally began to bear fruit for autism. In the Spring and again in the Fall, researchers reported successful application of GWAS technology to ASD.
GWAS is a powerful analysis technique that allows researchers to sift through hundreds of million of bits of genetic data to identify changes to the genetic code that are associated with a disease. Because the approach is not based on any specific biological hypothesis, scientists can cast the broadest experimental net possible, and use sophisticated statistical methods to establish the disease association. In recent years, GWAS has been successful in identifying susceptibility genes for such diverse conditions as macular degeneration, diabetes, rheumatoid arthritis, Crohn’s disease, and bipolar disorder. In April 2009, a large team of scientists led by investigators at Children’s Hospital of Philadelphia, reported results from the first successful GWAS study in autism. Tens of thousands of DNA samples are required for GWAS to produce meaningful results, so working with collaborators that included members of the Autism Genome Project, the researchers pooled samples from the Autism Speaks-funded Autism Genetic Resource Exchange (AGRE) combined with many other collections. The result was identification of a DNA variant associated with the genes cadherin 10 and 9, which are responsible for creating molecules that facilitate the formation of neural connectivity. This finding is consistent with accumulating evidence suggesting abnormal interactions between neurons may be at the core of the deficits seen in autism.
The idea that faulty connections between neurons plays a major role in ASD was further supported with the publication of the second autism GWAS study in October. Also working with AGRE and members of the Autism Speaks-funded Autism Genome Project, a collaboration led by investigators from Boston’s Autism Consortium and Johns Hopkins University used a very different statistical approach to discover an association between ASD and the gene semaphorin-5A. Similar to the cadherins identified in the first study, semaphorin 5A is thought to play an important role in neural development.
Taken together, these two groundbreaking studies confirm the potential for GWAS to make successful contributions to our understanding of autism genetics. Remarkably, out of the approximately 20,000 different human genes the experiments could have identified, the genetic variations that were uncovered are genes involved in brain development, serving to expand and reinforce our current thinking about biological mechanisms of autism. Like all new findings, they continue to focus the attention of the scientific community on the next directions for research and exploration.
Update since this story was published: DNA technology has once again advanced dramatically. New high-throughput techniques have finally made it possible to sequence entire stretches of genes, known as exons, in large numbers of patients. At the end of 2009, stimulus funds from the American Recovery and Reinvestment Act were awarded to investigators from the Autism Genome Project and the Autism Consortium who will use these new techniques to conduct a very detailed examination of 1,000 different genes linked to autism using several thousands of families who have kindly provided their DNA.
5|25: Celebrating Five Years of Autism Science Day 18: Unmet Medical Needs Documented for Autism Families
In honor of the anniversary of Autism Speaks’ founding on Feb 25, for the next 25 days we will be sharing stories about the many significant scientific advances that have occurred during our first five years together. Our 17th item, Recovery from Autism Spectrum Disorders, is from Autism Speaks’ Top 10 Autism Research Events of 2008.
For decades, autism spectrum disorders have been assumed to be life-long conditions. Recently, evidence has begun to emerge suggesting that a significant minority of children with well-documented autism spectrum disorder (ASD) can recover; in 2008 the first research publication to define and review recovery was released, placing the percentage of children who recover in the range of 3-25%.
In December 2008, a team of researchers from the University of Connecticut and their colleagues published an inspiring and provocative article documenting cases of recovery in autism. Recovery was defined as previously having had clearly defined ASD but currently no longer meeting criteria for any ASD. Furthermore, the recovered individual is now learning and using skills with a “quality that reaches the trajectory of typical development in most or all areas.” Using these criteria, the research team documented and followed a group of children, now between 8-18 years of age, with a history of ASD who are now “recovered.” The authors point out that children who recover from autism may nevertheless be at risk for other challenges, such as subtle difficulties with some aspects of language, anxiety, or learning disabilities.
In a previous study, the same researchers reported several cases of ASD that evolved into ADHD with no autism. Interestingly, most of these children had evidence of early regression and recurrent ear infections. Most had also received early intensive behavioral intervention. Recent outcome studies have shown that core symptoms of autism tend to improve by adulthood, especially difficulties in the areas of communication. Several outcome studies have found that about 10-20 percent of adults previously diagnosed with ASD no longer meet criteria for the condition.
How can recovery occur? One clear possibility is that successful treatment moved children who had ASD off of the spectrum. However, as the researchers point out, since most children who receive even the best and most intensive intervention do not recover, treatment alone cannot be the explanation. Both treatment and inherent characteristics of the child are likely to explain recovery. The research team therefore looked for child characteristics that predict optimal outcome, identifying higher IQ, receptive language ability, verbal and motor imitation, motor development, and an early age at diagnosis and initiation of treatment as promising predictors. In the majority of studies that report recovery, behavior intervention was used alone or in combination with other therapies.
The authors point out that although early intervention is associated with optimal outcome, this fact should not be used as an argument against the need for intervention in older children in light of the growing evidence of brain plasticity throughout the life span. Finally, this thoughtful article considers a wide range of biological mechanisms that may help explain the process of recovery. Future research directions will now provide us with insights into ways of improving the outcomes – and the chances for recovery – for all individuals with ASD.
Update since this story was first run: In 2009 researchers reported in the journal Pediatrics that they had used the National Survey for Children’s Health, a voluntary, parent-reported survey, to examine ASD prevalence in the US. Among other surprising results, they discovered that a substantial portion of parents reported their children had previously been diagnosed with an ASD but did not currently have the condition.