Report to Congress on Autism: Children's Health Act of 2000

Fiscal Year 2006

Prepared by the National Institute of Mental Health
National Institutes of Health
Department of Health and Human Services

Executive Summary

This is the annual Report to Congress on Autism required by Public Law 106-310, the Children's Health Act of 2000. The report provides an overview of activities conducted by the National Institutes of Health (NIH), the Centers for Disease Control and Prevention (CDC), and the Health Resources and Services Administration (HRSA) concerning the implementation of each section of the Act. In 2006, the NIH, CDC, and HRSA continued to make substantial progress in the research, diagnosis, and treatment of autism, in addition to enhancing education and public outreach activities. NIH continues to support the Studies to Advance Autism Research and Treatment (STAART) Network, which is composed of eight centers. NIH, in partnership with the Environmental Protection Agency (EPA), also funds the Centers for Children's Environmental Health and Disease Prevention and had expanded activities of the Collaborative Programs of Excellence in Autism (CPEA). The CDC oversees the National Autism and Pervasive Developmental Disabilities Surveillance Program, the Centers of Excellence in Autism and Pervasive Developmental Disabilities Epidemiology, and the autism awareness campaign - Learn the Signs. Act Early. HRSA continues to support two long-standing programs for the training of health professionals: the Leadership Education and Neurodevelopmental Disabilities Program and the Developmental-Behavioral Pediatrics Program. Further, HRSA has continued to fund the development of comprehensive, community-based service systems for children with autism and their families. In addition to the large programs and centers supported by the NIH, CDC, and HRSA, these agencies engage in a number of collaborative efforts to collect, store, and disseminate information in order to enhance autism research, services, and outreach.

Introduction

Autism is a complex neurobiological disorder that causes impairment in thinking, feeling, language, and the ability to relate to others. Autism is part of a group of disorders called autism spectrum disorders (ASDs), also known as pervasive developmental disorders. ASDs range in severity, with autism being the most debilitating form, while other disorders, such as Asperger syndrome, produce milder symptoms. Autism is usually first diagnosed in early childhood and persists throughout the lifetime of the individual. Autistic behaviors not only make life difficult for people with autism but also make life hard for their families, health care providers, and teachers. Families coping with this disorder are searching for information about the causes, diagnosis, treatment, and prevention of autism. Presently, there are no fully effective means to prevent, treat, or cure the disorder. Early intervention is critical for affected children to gain maximum benefit from current therapies. Although the full cost to society is unknown, autism affects all racial, ethnic, and social groups and causes tremendous economic and social burden.

Purpose of the Report

Public Law 106-310, the Children's Health Act of 2000, was signed into law on October 17, 2000. Division A, Title I, of the Act authorizes the Secretary of Health and Human Services (HHS) to conduct certain activities relevant to autism and pervasive developmental disorders, as follows:

• Section 101: Expansion, Intensification, and Coordination of Activities of the National Institutes of Health with Respect to Research on Autism;
• Section 102: Developmental Disabilities Surveillance and Research Programs;
• Section 103: Information and Education;
• Section 104: Interagency Autism Coordinating Committee; and
• Section 105: Providing this report to Congress.

Descriptions of the requirements mandated by each Section are provided below:

Section 101 authorizes the Director of NIH, acting through the Director of the National Institute of Mental Health (NIMH), to expand autism research activities and to support the specific planning and establishment of no fewer than five Centers of Excellence in Autism Research. Each Center should conduct basic and clinical research on the research topics of the causes, diagnosis, early detection, prevention, control, and treatment of autism. Collectively, the centers should conduct research in the fields of developmental neurobiology, genetics, and psychopharmacology. Support to the centers is not to exceed a period of 5 years, but support may be extended for one or more additional periods based on appropriate peer review. In order to facilitate research, Section 101 also authorizes a program through which samples of tissues and genetic material should be collected, preserved, and shared. Furthermore, the Director should provide a means through which the public may obtain information about existing and planned programs on autism at the NIH, and the Director should be able to receive comments from the public about these programs.

Section 102 authorizes the Secretary of HHS to act through the Director of the CDC to create a surveillance program for the collection, analysis, and reporting of data on autism and pervasive developmental disabilities. This portion of the Act requires the establishment of three regional Centers of Excellence for the purpose of collecting and analyzing information on the number, incidence, correlates, and causes of autism and pervasive developmental disorders. The section also calls for establishing a clearinghouse for the collection and storage of data generated by the surveillance programs. The clearinghouse will facilitate the coordination of research and policy development relating to the epidemiology of autism.

Section 103 authorizes the Secretary to establish and implement a program to provide education and information to health professionals and the general public on autism, including advances in the diagnosis and treatment. Continuing education programs should be provided to scientists, physicians, and other health professionals who provide care for patients with autism.

Section 104 stipulates that the Secretary establishes a committee to be known as the Interagency Autism Coordinating Committee (IACC) to coordinate all efforts within HHS concerning autism. The Committee is to be composed of the Directors of the relevant NIH Institutes, the CDC, and other agencies and officials that the Secretary determines to be appropriate. The Secretary also may appoint to the IACC parents or legal guardians of individuals with autism or pervasive developmental disorders, as well as representatives of other governmental agencies that serve children with autism, such as the Department of Education.

Section 105 requires the Secretary of HHS to submit an annual report to Congress "concerning the implementation of this title and the amendments made by this title." The following report summarizes the HHS activities in FY 2006 pertinent to each section of Division A, Title I, of the Children's Health Act of 2000.

Section 101: Expansion, Intensification, and Coordination of Activities of the National Institutes of Health with Respect to Research on Autism

a. Expansion, Intensification and Coordination of NIH Activities

Six Institutes are members of an internal NIH coordinating group that is separate from the IACC created in P.L. 106-310. This group, the NIH Autism Coordinating Committee (NIH/ACC), is composed of the NIMH, the National Institute of Child Health and Human Development (NICHD), the National Institute of Neurological Disorders and Stroke (NINDS), the National Institute on Deafness and Other Communication Disorders (NIDCD), the National Institute of Environmental Health Sciences (NIEHS), and the National Institute of Nursing Research (NINR). In addition, a staff representative from the National Institute of Allergy and Infectious Diseases (NIAID) participates in NIH/ACC meetings.

The NIH/ACC coordinates autism research activities funded and conducted by the various NIH Institutes. Representatives from the NIH/ACC attend meetings of the IACC and act as liaisons between the two committees, ensuring that NIH addresses IACC concerns and issues. As co-chairs of the NIH/ACC, the Director of NIMH and the Director of NICHD oversee those activities. The Secretary of HHS delegated to NIH the authority to convene the IACC, which NIH then delegated to NIMH. Therefore, the NIMH Director serves as chairperson of the IACC.

Over the past few years, NIH has considerably expanded its autism research portfolio and enhanced its coordination of autism research. NIH support of autism research grew from $22 million in FY 1997 to approximately $102 million in FY 2006. This represents an increase from 0.17 percent of NIH's budget in FY 1997 to 0.35 percent in FY 2006. The Institute members of the NIH/ACC have made a clear commitment to the broad intensification of autism research efforts called for in the Act. These efforts include a large number of grants, contracts, and intramural research programs distributed across the NIH.

In FY 2006, NIH autism research activities included the following:

The NICHD/NIDCD Network on the Neurobiology and Genetics of Autism: Collaborative Programs of Excellence in Autism

Established in 1997, the NICHD/NIDCD Network on the Neurobiology and Genetics of Autism currently consists of nine Collaborative Programs of Excellence in Autism (CPEAs). Investigators within the CPEAs have characterized more than 2,200 families with autism, the world's largest group of well-diagnosed individuals with autism for whom both genotypic and extensive phenotypic data are available for researchers to study. This network conducts basic and clinical research on the possible genetic, immunological, neurobiological and environmental causes of autism. The network also investigates the developmental course of autism and how the development and function of brain structures relate to autism. These undertakings require that each CPEA implement a cohesive, site-specific, multidisciplinary research program on the causes, brain substrates, functional characteristics, and clinical development of autism spectrum disorders. In addition, each site must participate in a trans-network collaborative study for which no single site has sufficient expertise and/or subject population.

The major CPEA sites are located at Boston University, Boston; University of California, Los Angeles; University of California, Davis; University of Washington, Seattle; University of Pittsburgh, Pittsburgh; University of Rochester, Rochester; University of Utah, Salt Lake City; University of Texas, Houston; and Yale University, New Haven. Over the last 9 years, individual CPEA sites completed genetic studies of autism; undertook studies of early brain function and abnormal brain anatomy in children with autism; developed methods for early recognition and diagnosis of autism and devised a new method for assessing social functioning in individuals with autism; furthered the characterization of distinct subtypes, or phenotypes, of autism spectrum disorders; conducted intervention studies using randomized clinical trials; and described environmental factors associated with improved development in children with autism spectrum disorders. Scientific accomplishments from CPEA individual sites in 2006 include a major publication on the findings of the mirror neuron dysfunction in children with autism spectrum disorders in the journal Nature Neuroscience (January, 2006). Mirror neurons are activated when performing certain actions and when watching similar actions being performed, thus mirroring behavior. This publication compared the mirror neuron system (MNS) activation in response to observation and imitation of facial affect in children with autism to typically developing children. The investigators found that, in both imitation and observation of facial affect, typically developing children showed activity in a specific portion of the cortex, the right inferior frontal gyrus, the region identified as containing mirror neurons. Those with autism did not show MNS activity, thus children with autism may have a specific deficit in a circuit that would normally allow them to learn by imitating others. In 2002, NIH renewed the funding of the CPEA sites for an additional 5 years. NICHD and NIDCD plan to allocate $60 million during this time period to sustain and enhance the CPEAs.

Because of the large number of autistic individuals enrolled in the CPEA research programs, the network is able to undertake studies that would be difficult or impossible to conduct at a single research site. Completed network projects have evaluated the effectiveness of the hormone secretin in the treatment of autism; the candidate autism genes, HOXA and Reelin; executive functions (i.e., planning, reasoning, impulse control) in autism; language functions in autism; and a genetic linkage study of autism in siblings. During the past year, CPEA investigators published a network project on the relationship between head circumference and autism. The most striking finding of this study is that, although mean head circumference and rates of macrocephaly (enlargement of the brain) are increased in autism, there is a wide distribution of head circumference. The presence of a wide distribution underscores the heterogeneous clinical manifestations of autism. Another major milestone for the CPEA genetics committee, the linkage study of autism in siblings, was published in August 2006 in the journal Molecular Psychiatry. By comparing differences between the genomes of 169 families with two siblings with autism and the DNA of another 54 families with autism and Asperger syndrome, the CPEA investigators found strong support for autism susceptibility genes on chromosome 7 and compelling but less strong evidence for genes on chromosomes 3, 4, and 11. This study also provided evidence for two genetic subtypes for autism, male versus female and early versus late onset. CPEA investigators also completed a network project on the cognitive profiles of preschool aged children with autism. Finally, as part of an ongoing network project, investigators have completed the database for the CPEA/STAART Girls with Autism Study, examining observable characteristics of 283 girls and women with autism. This is believed to be the largest sample of females with autism ever combined into a single dataset.

NIEHS/EPA Children's Centers

NIEHS, in partnership with EPA, supports autism research through a national network of Centers for Children's Environmental Health and Disease Prevention Research (NIEHS/EPA Children's Centers). Two of the centers, located at the University of California at Davis and the University of Medicine and Dentistry of New Jersey (UMDNJ; Piscataway), focus on identifying and understanding environmental influences in autism.

The UC-Davis center is conducting the first large population-based epidemiologic case-control study of children with autism (the Childhood Autism Risk from Genetics and the Environment, or CHARGE, study). A wide range of environmental and medical factors are being explored for their possible association with overall risk of autism or with risk in defined subgroups of children with autism. Seven hundred children have been enrolled to date and analysis of biologic samples and other data are ongoing. One area of focus is the possible dysregulation of the immune system in autism. Another area of focus is the establishment of models of human social behavior in mice and nonhuman primates. These models may then help the search to identify genetic factors by allowing controlled experiments to study the effects of environmental exposures on specific genes and how this in turn can cause disrupted social behaviors.

During FY 2006, the NIEHS/EPA Children's Center at the UMDNJ continued its enrollment of children in a unique study designed to comprehensively evaluate the autistic child's personal, residential, and community environments. A primary goal of this study is to compare environmental exposures of children with regressive vs. non-regressive forms of autism. Other projects conducted at this Center are using cellular and animal models to study how known neurotoxicants interact with neuronal functioning and genetic expression that have potential relevance to autism. Using methylmercury as a model neurotoxicant, Center investigators published a recent study demonstrating a novel mechanism by which environmental toxicants can alter cell cycle regulation and impact early brain development. Another study described a novel animal model of autism, based on administration of sodium valproate to mice during the prenatal or early postnatal period. The valproate-treated mice displayed developmental deficits that emerged in a fashion similar to the clinical signs of autism. This strategy may prove useful for the assessment of the deleterious effects of early stressors (including drugs, illness and environmental toxicants) on neurobehavioral development. Also, based on recent preliminary clinical findings of increased susceptibility of children with autism to oxidative stress, investigators are using animal models to begin to explore potential intervention strategies using enhanced antioxidants as a means of counter-acting oxidative stress.

A new round of competition for the NIEHS/EPA Children's Centers was announced in August 2005. Applications were received from existing centers as well as new investigative groups that propose research to explore environmental etiologies of childhood disorders affecting the nervous and/or endocrine systems, with autism being one of several disorders of interest. Based on the results of competitive merit review, the NIEHS and EPA awarded a second 5-year grant to UC-Davis in August 2006 to continue its investigation of immunologic, genetic and environmental contributors to autism. MARBLES (Mothers of At Risk Babies Learning Early Signs), a new project being initiated at this center, will focus on a high-risk group, mothers who have a child with autism and are pregnant or plan to become pregnant. Investigators will track mothers throughout pregnancy and their offspring for the first 3 years of life, with the goal of measuring prenatal and postnatal exposures that may affect risk of developing autism.

b. Centers of Excellence

The STAART Network continues to make considerable progress in autism research. The STAART Network was born out of the Children's Health Act of 2000, which called for NIH to establish at least five Centers of Excellence in Autism Research. In response to this charge, NIH implemented a program that meets and exceeds the specifications of the Act regarding the organization, scientific goals, and other characteristics of the program. The goal was to establish several research centers that would unite expertise, infrastructure, and resources focused on major questions about autism. In 2002, two centers were funded; one at the University of North Carolina (Chapel Hill) and the other at Yale University (New Haven). In 2003, six additional centers were funded by five participating NIH Institutes (NIMH, NINDS, NICHD, NIDCD, and NIEHS). The six centers are located at the University of Washington, Seattle; the University of California, Los Angeles; Boston University, Boston; the University of Rochester, Rochester; the Kennedy Krieger Institute, Baltimore; and Mt. Sinai Medical School, New York. In 2005, NIH spent approximately $9.5 million in total funds to support the STAART Network. NIH funding supports the eight centers, the data coordination center, and collaborative projects among the centers. The Steering Committee of the STAART Network determines the exact nature of the cooperative studies.

The STAART centers are contributing to the understanding of autism by investigating areas such as early detection through behavioral and/or biological markers, efficacy of early behavioral interventions, early course of core features, biological basis of the core deficits, and behavioral treatments for social deficits; efficacy trials for pharmacotherapy, genotypic and phenotypic response to treatment; and identification of susceptibility genes. As a requirement of participation in the STAART Network, each center has at least one treatment project. A collaborative, multisite psychopharmacology clinical trial was launched in 2004. A feasibility study for a second collaborative psychopharmacology trial is currently under way.

The STAART centers interact with the CPEA Network through a number of mechanisms, including a common brain imaging subcommittee and a combined common measures/data sharing subcommittee. In 2003, the NIH established a data-coordinating center (DCC), designed specifically to expedite and to maximize the analysis of data generated by both the CPEA research projects and the STAART Network. This DCC provides administrative support, project management support, and data management support, as well as customized system applications for both the CPEA and the STAART centers. The major focus of the DCC has been the formation of a warehouse for collecting data on common measures for both networks. This warehouse is now fully operational, with Centers collecting data on common measures from each site at regular intervals. The DCC also continues to provide project and data management support for the pharmacologic, multisite randomized control trials of the STAART Network. During the past year, scientific advisors requested that the CPEA and STAART Networks create a cross-network public Web site to provide an additional venue for research dissemination. The Web site was officially released at the joint CPEA and STAART annual meeting in November 2005 and may be viewed at http://www.autismresearchnetwork.org/an/.

The STAART and CPEA centers are fostering potential collaborations to combine data from their diverse samples in order to increase the ability to detect deviations in brain development in relationship to clinical features (e.g., gender, age, behavioral symptoms). For example, CPEA investigators initiated a collaborative project between the CPEA and STAART Networks to apply structural brain imaging to the study of autism. The goal of this project is to determine whether investigators can pool existing data from different sites to provide reliable, valid findings that address questions about the brain structures that are affected across the life span in autism.

Another example of a multisite STAART and CPEA collaboration is the Girls with Autism Study, which is examining phenotypic characteristics of 283 girls and women with autism whose data were contributed from the CPEA and STAART network sites. This sample may be the largest sample of females with autism ever studied for this purpose. Data from the females with autism will include characteristics such as age, IQ, autistic symptoms, and adaptive behavior. In addition, a sample of more than 800 comparable males with autism is available for comparison. The project will be able to identify relationships among phenotypic characteristics, which may differ according to sex. These results are expected to lead to further hypotheses that can be investigated in large scale studies using representative sampling methods.

With the expiration of the STAART and CPEA Networks in 2007 and 2008, the NIH has created a new, unified centers program in order to maximize coordination and cohesion of NIH-sponsored efforts. This will avoid duplication, allow the most efficient use of resources, and involve a larger number of investigators. In December 2005, the NIH issued a Request for Applications (RFA) to solicit applications for Autism Centers of Excellence (ACE) with an application deadline in August 2006. Research projects will focus on identifying causes and preventive interventions for autism, as well as improved pharmacological and behavioral treatment. Examples of projects may include identifying the biological and/or behavioral markers to develop indices of risk for the development of autism in infants; identifying environmental factors (e.g., viruses, medication, lifestyle factors, environmental chemicals) that contribute to the development of autism; multisite randomized clinical trials to identify moderators and effective ingredients (e.g., dose, intensity, mode of delivery, age of onset) of early intervention treatments; and identification of susceptibility genes and animal models of autism for further study of phenotypic characteristics of autism. Applications will be reviewed in November 2006, with the earliest anticipated award dates in the spring of 2007. The NIH plans to commit funds at least at the current funding level for the STAART and CPEA centers. The NIH Guide Notices for these RFAs may be viewed at:

http://grants.nih.gov/grants/guide/rfa-files/RFA-HD-06-016.html
http://grants.nih.gov/grants/guide/rfa-files/RFA-HD-06-004.html

c. Facilitation of Research

NIH facilitates research on autism spectrum disorders through a number of mechanisms, including soliciting research applications (i.e., RFAs and program announcements [PAs]), sponsoring meetings and workshops, funding investigator-initiated studies, and supporting research infrastructure. Examples of these efforts are described below.

The NICHD and the NIDCD continue to partner with Autism Speaks in support of the activities of the High Risk/Baby Sibling Research Consortium. The Consortium continues to hold monthly conference calls to facilitate exchange of research ideas, to establish core common measures, and to plan for annual meetings. Over the past year, the Consortium has made several significant accomplishments. First, a memorandum of agreement between collaborating investigators was developed in which a Consortium primary project was outlined. The aims of the primary project are to examine recurrence rates of ASDs and broader developmental outcomes in infant siblings of individuals with ASD and to identify factors that may influence recurrence rates among infant siblings of individuals with ASD. Data across Consortium sites will be combined to address these goals when outcome data at 36 months of age become available. This project is significant for the Consortium since it is highly unlikely that any one individual site will have sample size large enough to address recurrence risk. Second, the Consortium members published a paper entitled "Studying the Emergence of Autism Spectrum Disorders in High-Risk Infants: Methodological and Practical Issues" in the Journal of Autism and Developmental Disorders, addressing significant methodological, ethical, and practical issues such as the use of comparison groups and the needs of infants suspected of showing early signs. Finally, a prospective head circumference project, which is the first collaborative project of the Consortium, is also making progress., The main objective of this project is to assess head growth prospectively in high-risk infants, and correlate these data with diagnostic outcomes. Recruitment of sibling and comparison groups is on target; 790 siblings and 323 comparison participants have been recruited and data collection has begun. It is anticipated that database development and data analysis will begin in 2007.

NIH Institutes have continued to support brain tissue bank collections and tissue distribution resources at several sites. Researchers require brain tissue in order to uncover the underlying neuropathology of autism, and new molecular methodologies to study postmortem brain tissue provide researchers with a high-resolution window into the inner workings of the brain. Activities in 2006 continued to focus on a combined effort by NIMH and NIDCD to supplement the Harvard Brain Tissue Resource Center (whose principal funding comes from NINDS and NIMH) for the creation and maintenance of a National Autism Brain Bank. In addition to other federally funded efforts, this national resource will help collect, store, and disseminate postmortem human brain specimens for the study of autism. Other federally funded efforts include the NICHD's Brain and Tissue Bank, which collects, stores, and distributes brain and other tissues of individuals with autism and other developmental disorders for autism research as well as for control purposes.

Most training interventions have been tested with mothers of autistic children; few have been tested with fathers. NINR-supported investigators have demonstrated that fathers can be taught skills that they can use to increase the child's social interactive behaviors and vocalizations - two behavioral deficits in children with autism. In turn, it was also demonstrated that fathers can effectively train mothers to use these same skills. Current funding will support (a) the evaluation of this in-home training intervention on parental stress and family cohesion and (b) the development of a Web-based version of this parent training intervention.

The NIEHS worked cooperatively with the CDC to convene an external Expert Panel on May 4, 2006, in Research Triangle Park, North Carolina, for the purpose of discussing the feasibility and utility of new studies that could be conducted with the Vaccine Safety Datalink (VSD) to examine a possible association between risk of autism and exposure to thimerosal-preserved vaccines. The VSD was developed by CDC to enable continual monitoring of vaccine safety through record linkage of vaccine administration data with potential adverse events in several large populations served by Managed Care Organizations (MCOs). The collective expertise of the panel included clinical and epidemiologic research, biostatistics, neurotoxicology, and risk assessment. Representatives from the NIH Institutes that support autism research, the EPA and several major autism advocacy organizations were invited to attend this meeting. The meeting included opportunities for public comment. A final report of the Expert Panel is in preparation to be transmitted to Congress in November 2006. The Panel report noted that the proposed use of the VSD for an ecologic study to compare autism rates before and after the removal of thimerosal from most childhood vaccinations would be uninformative and potentially misleading due to the cumulative effect of several important limitations of the VSD. The Panel endorsed two additional types of studies using the VSD focused on siblings of individuals diagnosed with AD/ASD. The NIEHS will work with scientists at the CDC, scientists in the VSD network, and scientists at the California State Department of Developmental Services to determine the feasibility of the studies endorsed by the Panel.

Five NIH Institutes (NIMH, NINDS, NIDCD, NICHD, NIEHS), the National Alliance for Autism Research (NAAR), Cute Autism Now (CAN), and the Southwest Autism Research and Resource Center (SARRC) sponsored an RFA entitled "RFA MH-05-007: Identifying Autism Susceptibility Genes." The Canadian Institutes of Health Research and the Irish Health Research Board also were involved in the writing of this RFA. The goal of this effort was to solicit large-scale molecular genetic research projects to identify specific genes and gene variants in localized chromosomal regions that produce susceptibility to autism. Five grants (representing three projects) were awarded to researchers at the State University of New Jersey, Robert Wood Johnson Medical School, University of Iowa, Cold Spring Harbor Laboratory, and Emory University. The voluntary organizations and the NIH Institutes established a pool of funds that were used to make 5-year awards that totaled $10.8 million. These projects represent the current state of the art in human genetics tools and technologies for dissecting the genetic basis of common human diseases. The projects are expected to result in the identification of specific genetic variants that contribute to autism susceptibility. The NIH Guide Notice for this RFA can be found at https://grants.nih.gov/grants/guide/rfa-files/RFA-MH-05-007.html.

Fragile X syndrome (FXS) is the most common cause of genetically-inherited mental impairment, ranging from subtle learning disabilities to severe cognitive or intellectual challenges, such as autism. Approximately 15-25 percent of children with FXS also have autism, and about 2.5-6 percent of children with autistic features have FXS. Therefore, understanding the molecular basis of FXS offers exciting new insights into the etiology and pathophysiology of autism. NIMH, NINDS, and NICHD have entered into a public-private partnership with the Canadian Institutes of Health Research, the Irish Health Research Board, CAN, NAAR, Autism Speaks and the Fragile X Research Foundation (FRAXA) to jointly sponsor a PA entitled "PA-05-108: Shared Neurobiology of Fragile X and Autism." The goal of this PA was to solicit applications to characterize, understand and treat etiological and pathophysiological mechanisms common to both FXS and autism. The NIH Guide Notice for this PA can be found at http://grants.nih.gov/grants/guide/pa-files/PA-05-108.html.

NIMH issued PA-05-106, "Deep Sequencing and Haplotype Profiling of Mental Disorders." The goal of this PA is to solicit applications that implement large-scale studies and innovative analytical designs to identify and characterize the different gene variants that influence risk for a given mental disorder. These research developments, whether fundamentally new or evolutionary, may lead to paradigm shifts in the field. Applications written in response to this PA may propose new technologies for cost-effective, whole-genome analysis and in-depth sequencing of candidate genes in families with autism or in samples of unrelated individuals with autism (and other mental disorders). Results from research funded under this initiative will have direct implications for diagnosis, treatment, and ultimately, prevention of autism and other mental disorders. The NIH Guide Notice for this PA can be found at http://grants.nih.gov/grants/guide/pa-files/P A-05-106.html.

A large autism genetics project at Johns Hopkins University was funded by NIMH in 2005, employing state-of-the-art technology to study how genetic variation among individuals could influence the risk of developing autism. As mentioned earlier in this report, this project has already yielded important results that point to regions on chromosomes 7, 10, and 19 as potential areas of genetic variation in children with autism.

NINDS is supporting a 5-year, $13 million epidemiological study of a large Norwegian birth cohort to explore how various genetic and environmental factors contribute to the development of autism and other neurodevelopmental disorders. This project will evaluate 75,000 women and their infants who are enrolled in the Norwegian Mother and Child Cohort Study (also known as MOBA). The prospective study is examining multiple potential risk factors for autism and their interactions with genetic risk factors, such as infection history, very low birth weight, dietary and environmental exposure including methyl mercury, and vaccination history.

NINDS continues to support promising research on the genetics of autism, including support for the development and expansion of resources for research. NINDS currently funds an infrastructure development grant that enables research groups located in the United States, Canada, Europe, and Israel to collaborate on gene discovery for autism. This Autism Genetic Cooperative (AGC) has created a common genetic database, which will enable all AGC participants to pool data from their individual sample collections for more powerful analyses. The AGC also has launched a new Web-based network to help its participants function as a virtual laboratory. In conjunction with NAAR, AGC members convene an annual workshop to discuss new ideas and present various joint studies that have been carried out during the year. In addition, NINDS supports a number of studies aimed at identifying genes that contribute to autism. These studies are using a variety of approaches, from analyzing the genes and clinical characteristics of families with multiple affected members, families with sporadic cases, or a genetically isolated population, to applying new analysis techniques to the data in the AGRE and NIMH repositories.

The NIH/ACC is working with the NIH Center for Information Technology (CIT) to create and implement a National Database for Autism Research (NDAR). The NDAR is needed in order to achieve several of the goals of the IACC's Autism Research Matrix, such as "establish resources for genotype/phenotype studies (i.e., bioinformatics, genetic repository)." This database will allow researchers to share the raw materials of research and to make disparate databases available through a single source. NDAR will also assist scientists to reach consensus on common measures, data elements, and methodologies to enhance the comparison of data among various research centers.

NDAR will be used to facilitate data sharing in the Autism Centers of Excellence and will coordinate data with other Federal databases, such as the NIMH Autism Genetics Repository. To better serve the needs of researchers and to foster academic collaborations, NDAR will facilitate public-private partnerships, such as treatment studies conducted with privately funded networks, access to private registries, and other repositories for biological samples. NDAR will enhance communication between researchers and the public and will ensure the rapid dissemination of research findings into clinical practice. It is envisioned as a dynamic system with improvements and updates being added routinely to meet the most critical and valuable needs of the research community. The initial release of NDAR will form the foundation of subsequent releases that will provide an overall NDAR system with a focus on providing core clinical assessments and neuroimaging databases. It is anticipated that this initial release to ACE grantees will be in spring 2007.

d. Public Input

Parents and guardians of individuals with autism play a central role in the activities of the IACC and the NIH/ACC. As required by P.L. 106-310, parents are represented on the IACC and have collaborated on numerous NIH activities. Additionally, the biannual meetings of the IACC are open to the public and include time for public comment.

NIH maintains a close collaborative relationship with the autism advocacy community through numerous mechanisms. Advocacy groups representing parents and patients have co-funded research projects solicited through RFAs and PAs and have cosponsored numerous meetings and workshops. In general, NIH is committed to sharing information about NIH processes and research progress with the public and, in turn, is committed to incorporating public views into NIH activities, programs, and priority-setting. NIH offers many opportunities for public participation, such as participation in the NIH Director's Council of Public Representatives (COPR), individual Institute advisory councils and their meetings, and specially conducted public forums around the country. In addition, some Institutes, such as NIMH, involve public participants in the grant review process and Alliance for Research Progress meetings. The autism advocacy community has often been represented in these many venues.

Section 102: Developmental Disabilities Surveillance and Research Programs

a. National Autism and Pervasive Developmental Disabilities Surveillance Program

In 1998, CDC initiated the National Autism and Pervasive Developmental Disabilities Surveillance Program, one of the few programs in the world that conducts active, ongoing monitoring of the prevalence of ASDs in children. Data from the first year of monitoring were published in 2003, providing one of the most complete and comprehensive assessments of autism prevalence in a large U.S. metropolitan area (Atlanta, Georgia). The rate of autism found in this study (3.4 cases per 1,000 children) is higher than the rates found from studies conducted in the United States during the 1980s and early 1990s but is consistent with rates reported in more recent studies (mostly from Europe and Asia).

Since FY 2000, Congress has provided funding to enhance CDC's network of State-based autism surveillance programs. Collectively, these sites comprise the Autism and Developmental Disability Monitoring (ADDM) network. The ADDM network is the only collaborative project using similar methods to determine the prevalence of ASD based on the model methodology used by CDC's autism and developmental disabilities program in Atlanta. Investigators in CDC-funded ADDM Network programs are implementing active ASD surveillance systems that do not rely on professional or family reporting of children's recorded ASD classification. Rather, children's evaluation records are requested at various clinical and educational sources for review by study staff. Requests are based on a list of possible diagnostic codes in clinical settings or on special education eligibility classifications in educational settings. Children's records are screened for the presence of pre-defined behavioral triggers mentioned in clinical/educational evaluations. Those meeting initial screening criteria are abstracted in full to record all available evaluation data through the target study year. Evaluations from all data sources are compiled into one composite record for each child. When record abstraction is completed for the study year, these composite records are systematically reviewed by an independent team of clinicians in order to determine case status. Individual programs will maintain unique personal identifiers to enable data collection and management processes, generate estimates of data accuracy and completeness, and link abstracted data to vital records and other external datasets. However, prior to submitting surveillance data to CDC for pooling with other sites' data, all personal identifiers will be removed, and no linked study I.D. will be transmitted. Thus, the pooled surveillance dataset will contain no identifiers or identifiable data.

The ADDM Network seeks to develop or improve programs that track the number of children with ASDs in their States. The goal of the ADDM Network is to provide comparable, population-based estimates of the prevalence rates of autism and related disorders in different sites over time. The program has made significant strides in attaining its goal. From 1999 to 2006, up to 16 sites (including CDC) were collaborating via the ADDM Network to determine the prevalence and characteristics of children with ASDs in their study areas. Two prevalence reports and an ADDM Network evaluation paper will be released in February 2007 in the Morbidity and Mortality Weekly Report (MMWR) Surveillance Summaries. These joint summaries will detail the prevalence of ASDs in six areas of the United States for the year 2000 and 14 areas for the year 2002. Individual sites are currently working on site-specific analyses and reports. In addition, pooled datasets have been compiled for the study years 2000 and 2002, and several cross-site analyses are underway including reports on the prevalence of Cerebral Palsy and Mental Retardation. There are eight sites completing data collection and analysis for the study year 2004 with an expected report late in 2007.

In June 2006, 10 sites (Alabama, Arizona, Colorado, Florida, Maryland, Missouri, North Carolina, Pennsylvania, South Carolina, and Wisconsin) were awarded a 4-year cooperative agreement to further investigate the prevalence of autism and other developmental disabilities in study years 2006 and 2008. Data collection has begun for study year 2006 in all the sites.

The Memorandum of Agreement (MOA) that allowed the Atlanta program to access school records expired in December 2005. However, CDC and the Georgia Department of Education have entered into exploratory conversations to discuss other possible collection methods, with the hope of allowing the Atlanta program to continue.

b. Centers of Excellence in Autism and Pervasive Developmental Disabilities Epidemiology

In September 2001, CDC funded four Centers for Autism and Developmental Disabilities Research and Epidemiology (CADDRE) to conduct collaborative studies on the number, incidence, and causes of autism spectrum disorder and related developmental disabilities. In September 2002, CDC funded a fifth center. The five centers and their surveillance regions are: (1) Johns Hopkins University, which is identifying cases of autism in northeastern Maryland; (2) the University of Pennsylvania, which covers the Philadelphia metropolitan area; (3) the Colorado Department of Public Health, which concentrates on identifying cases in the Denver area; (4) the California Department of Health Services, which is ascertaining cases of autism statewide, with more intensive monitoring in the San Francisco Bay area; and (5) the University of North Carolina, which covers the Raleigh and Chapel Hill areas.

For the first funding cycle (2001-2006), each CADDRE grantee had three core objectives: to establish a multisite collaborative epidemiologic study focused on autism; to conduct surveillance of autism and other developmental disabilities; and to conduct site-specific investigator-initiated studies on autism. Significant accomplishments for CADDRE include establishing, implementing and completing the 2000 and 2002 surveillance study years; completing site-specific investigator-initiated studies, many of which contributed to the refinement of the National CADDRE Study; and sharing information on ASDs and findings from their special studies through mailings targeted to key audiences, news releases to the lay and professional media, and sponsored symposia on ASDs.

The activities for the second funding cycle (2006-2011) will focus on the multisite collaborative epidemiologic study on autism. The multisite collaborative epidemiologic study was designed by CADDRE during the first funding cycle to address critical gaps in our understanding of potential risk factors and causes of autism. Known as the National CADDRE Study: Child Development and Autism, the study will address features of the broad autism phenotype; primary risk factor domains, including infection or abnormal immune function, abnormal hormone function, genetic factors, and gastrointestinal function; substance use during pregnancy; sociodemographic factors; occupations; and specific mercury exposures.

A case-cohort study design has been adopted for the National CADDRE Study. Study participants will include children ages 2-5 years and their parents. All study children will be drawn from the cohort of children born among residents in the CADDRE site study areas in select birth years. Three groups of children will be selected: children identified with autism spectrum disorders, children identified with other developmental problems, and a random sample of all cohort children (most of whom are typically developing). Data collection will consist of six main components: primary caregiver interviews, medical record abstraction, primary caregiver self-administered questionnaires, child developmental evaluation, child physical exam, and bio-sampling from biological parents and child. Common data elements across all sites will be pooled for analysis.

Several steps in the development of the National CADDRE Study have already been completed. The protocol has been written and initial IRB approval obtained. In addition, site-specific advisory boards have been established to review the study materials and the study design and focus groups with parents of children with and without developmental disabilities were conducted to obtain additional feedback on the study design and feasibility of the study. The study instruments and materials have been pilot tested and field manuals, field staff training protocols, and quality control protocols for all aspects of the National CADDRE Study field work have been developed and train-the-trainer sessions for field implementation procedures have been held. Data sharing protocols and analysis plans have been developed, and the CADDRE Information System (Web-based subject tracking and data collection application) has been established.

c. Clearinghouse

As part of the Centers of Excellence in Autism and Pervasive Developmental Disabilities Epidemiology, CDC established a clearinghouse for the collection and storage of data and information in order to facilitate the establishment and operation of surveillance projects and epidemiological studies of autism and related pervasive developmental disabilities. Through the clearinghouse, CDC makes available any materials or information developed by the CDC-funded centers and States that may be useful for the CDC-funded researchers. Examples of material include publications of epidemiological studies; data management manuals; training materials; research protocols, including questionnaires and other instruments; information on privacy and confidentiality of data; community outreach strategies; and educational materials for professionals, families, schools, and the general public. In addition, the State surveillance programs have an Education and Outreach Committee, which has continued its efforts to increase awareness of autism in each State by assessing information needs. The goal of these programs is to increase knowledge and awareness among service providers, parents, and the general public. In addition to the larger group, each site also conducts local outreach activities. For example, the Education and Outreach Committee for the surveillance program based out of the Medical University of South Carolina has given more than 25 presentations to local audiences, has had multiple meetings with local stakeholders, and is holding an autism conference for the region.

In September 2002, CDC launched a Web-based Autism Information Center. The information center focuses on the activities of Federal and federally funded programs and the resources offered by these programs. The center includes information for the general public, families, and professionals. Current topics include general information about autism spectrum disorders; activities at CDC and other Federal agencies; State activities funded by CDC; education and services resources for families; resources for researchers; and activities to help children use the Internet to learn more about ASDs. The information center can be accessed from http://www.cdc.gov/autism.

In 2001, CDC completed and reported the results of a community-based prevalence study undertaken in response to parental concern regarding a possible elevated number of children with ASDs in Brick Township, New Jersey. The study found 6.7 cases of ASD per 1,000 children in the community, a rate similar to autism prevalence estimates from small investigations previously conducted in the United States and abroad. However, this was a small study conducted in just one community, making it difficult to generalize these findings to the larger population, further underscoring the need for dependable, large population-based autism prevalence data. In addition to providing information needed to answer questions about trends in autism, CDC's program and the eleven States that CDC supports to conduct autism monitoring in their regions will provide the vital background data necessary to evaluate other potential autism clusters.

Section 103: Information and Education

Under Title 1 of the Public Health Service (PHS) Act, Section 103 authorizes the Secretary to establish and implement a program to provide information and education on autism to health professionals and the general public, including information and education on advances in the diagnosis and treatment of autism and training and continuing education through programs for scientists, physicians, and other health professionals who provide care for patients with autism. Funds may be used to provide stipends for health professionals who are enrolled in training programs under this section.

In FY 2006, HRSA's Bureau of Health Professions supported the Quentin N. Burdick Program for Rural Interdisciplinary Training to enhance the interdisciplinary education and training of health professionals in rural communities and to address rural health care workforce problems. Projects under the Burdick Program have supported the interdisciplinary education and training of health professionals to address a variety of health care problems, including behavioral/mental health and developmental disabilities in children and adults. The Burdick Program funded the West Virginia University Center for Excellence in Disabilities, which addressed the interdisciplinary education and training of health professionals in developmental disabilities, including autism. The purpose of this project was to improve access to person-centered, quality home health care through the development of clinically competent health care professionals, and to support a diverse and culturally competent health professions workforce. The program provided interdisciplinary preservice training for a person-centered approach to home assessments for individuals with disabilities, including those with developmental disabilities and autism, chronic conditions, and the elderly. The Quentin N. Burdick Program for Rural Interdisciplinary Training ended in 2006.

HRSA's Maternal and Child Health Bureau (MCHB) has two long-standing programs that are relevant to the training of health professionals to serve persons with autism and other developmental disabilities. MCHB's Leadership Education in Neurodevelopmental Disabilities (LEND) Program funds 35 programs across the United States to train individuals from a wide variety of professional disciplines to assume leadership roles and to ensure high levels of clinical competence to improve the health of children who have, or are at risk of developing, neurodevelopmental or other related disabilities such as autism and mental retardation. Interdisciplinary faculty and trainees include audiologists, dentists, health administrators, nurses, nutritionists, occupational therapists, physical therapists, physicians, psychologists, social workers, special education professionals, and speech language pathologists. The Developmental-Behavioral Pediatrics Program funds nine programs, located in institutions of higher learning, to enhance the behavioral, psychosocial, and developmental aspects of general pediatric care. The programs support fellows in behavioral pediatrics to help prepare them for leadership roles as teachers, researchers, and clinicians.

In 2006, the MCHB's Division of Services for Children with Special Health Care Needs (DSCSHN) continues to support the development of comprehensive, coordinated, community-based service systems for children with autism and their families. The DSCSHN provides grant support to the University of Wisconsin-Madison for the Waisman Center, which also serves as a local and national service model for coordination of care through a primary care, and for the National Medical Home Autism Initiative to help promote early identification and intervention for children and youth with ASD. The grant also supports coordination of other community-based services that support persons with ASD. In other efforts, the DSCSHN used recommendations from the ASD Service Roadmap drafted by the IACC Service Subcommittee to begin the development of ASD Service Guidelines. These guidelines assist healthcare providers with service coordination across the agencies that provide health and related services to children with autism.

In FY 2003, CDC laid the groundwork for an autism awareness campaign, Learn the Signs. Act Early. The focus of the campaign is to encourage early screening and detection of autism and other developmental disabilities in order to help children develop and reach their full potential. Congressional appropriations in FY 2004 for autism included approximately $2.2 million to support autism awareness activities. These funds are being used to launch the campaign and to produce and disseminate materials to parents and providers stressing the importance of early screening and intervention for children with disabilities, especially autism. In addition to continuing to support the existing core components, FY 2005 funding supported outreach to another important audience-the child care and early education community, which spends considerable time with young children and is in an excellent position to notice the first indications of potential problems.

Section 104: lnteragency Autism Coordinating Committee

a. Establishment

Section 104 mandated the establishment of an interagency autism coordinating committee to coordinate research and other efforts with regard to autism within HHS. Secretary Tommy Thompson delegated the authority to establish the IACC to NIH in April 2001. NIMH at the NIH has been designated the lead for this activity. The Committee has held nine semiannual meetings.

b. Membership

The Committee's primary mission is to facilitate the effective and efficient exchange of information on autism activities among the member agencies and to coordinate autism-related activities.

P.L. 106-310 specifies that the Secretary may appoint parents or legal guardians of individuals with autism or other pervasive developmental disorders to the Committee. Such appointments have proven vital to the conduct of the Committee's mission. In particular, public members of the IACC bring to HHS the concerns and interests of families and care providers who struggle with this disorder each day. The IACC serves as a forum, helping to increase public understanding of the member agencies' activities, programs, policies, and research, and to assure that those agencies are continually aware of the issues and concerns affecting individuals with autism, their families and all those who care for them. The Secretary has appointed four public members.

Government agencies represented in the IACC include the following: NIH/ACC members (NIMH, NICHD, NIDCD, NIEHS, and NINDS), HRSA, CDC (specifically, the Agency for Toxic Substances and Disease Registry and the National Center on Birth Defects and Developmental Disabilities), the Substance Abuse and Mental Health Services Administration, the Administration for Children and Families (specifically, the Administration on Developmental Disabilities), the Food and Drug Administration (specifically, the Center for Biologics Evaluation and Research), the Centers for Medicare and Medicaid Services, the Agency for Healthcare Research and Quality, the Office on Disability, and the Department of Education (specifically, the Office of Special Education and Rehabilitative Services, and the Institute of Educational Sciences). A summary of each meeting is posted when available on the NIMH Web site (see http://www.nimh.nih.gov/autismiacc/index.cfm).

c. Activities

The IACC has established subcommittees on autism screening and the organization of autism services. Both subcommittees are now working to coordinate activities among IACC members and with the relevant stakeholders in the medical and services communities.

IACC Autism Research Matrix

The House and Senate conferees considering the FY 2003 appropriations for the Departments of Labor, Health and Human Services and Education, Conference Report 108-10, requested that the IACC "convene a panel of outstanding scientists to assess the field of autism research, and to identify roadblocks that may be hindering progress in understanding its causes and best treatment options." In response to this request, the IACC convened a panel of science experts to document the roadblocks to understanding causes and best treatment options for autism, as well as goals and activities to overcome these roadblocks. A list of roadblocks was created, and the autism research matrix was designed to include goals and activities for the next 10 years. Goals and activities that comprise the autism research matrix generally fall within the following categories: characterization of autism (i.e., phenotype), screening, early intervention, school and community interventions, specific treatments, neuroscience, and epidemiology. After the science panel suggested items for the matrix in July 2003, the membership of the IACC approved the final version of the matrix at a public meeting on November 21, 2003. The Congressional Appropriations Committee Report on the State of Autism Research, summarizing the autism research matrix and plans for implementation, was submitted in April 2004 and may be found at http://www.nimh.nih.gov/autismiacc/CongApprCommRep.pdf. The plan for implementing the matrix included the April 2004 reissue of the PA "Research on Autism and Autism Spectrum Disorders" and the funding of projects that will advance individual matrix items. In addition, NIH sponsored a meeting in May 2004 to specifically address the need to improve methodologies and outcome measures for treatment studies.

Throughout the past 3 years, the matrix has provided a resource for directing the expansion and intensification of autism research. At its May 2006 meeting, the IACC agreed that this was an opportune time to evaluate progress on the research matrix. The IACC decided that the original panel members, along with new participants selected to broaden the expertise represented on the panel, should be invited to review the state of autism research and to evaluate research progress using the matrix as a guide. This meeting was convened in September 2006, and a draft summary report was presented at the November 2006 meeting of the IACC.

Autism Spectrum Disorders Services Roadmap

The services subcommittee of the IACC developed a "services roadmap" for ASD. The ASD Services Roadmap is intended to provide a national blueprint to enhance existing systems; expand services for children, youth, and adults with ASD and their families; and coordinate services across systems. The Roadmap was developed within the context of the President's New Freedom Initiative (NFI) and was based on Executive Order No. 13217, "Community-Based Alternatives for Individuals with Disabilities." The Order calls upon the Federal Government to assist States and local jurisdictions to implement swiftly the decision of the U.S. Supreme Court in Olmstead v. L.C., which states that "the United States is committed to community-based alternatives for individuals with disabilities and recognizes that such services advance the best interests of the United States." Thus, national impetus exists, through NFI, to reduce barriers to community services and independent living for all individuals with disabilities, including those with ASD.

In summer 2004, the services subcommittee of the IACC established a panel of experts to review the state of the field and to provide recommendations for expanding and improving ASD services. This diverse group, called the Expert Working Group (EWG), consists of members with special ASD expertise - service providers, physicians, educators, community program coordinators, researchers, individuals with ASD, and family members of individuals with ASD. Representatives of the EWG presented a status report to the IACC at the November 19, 2004, IACC meeting, which can be found at http://www.nimh.nih.gov/autismiacc/asdroadmap.pdf. Members of the services subcommittee have presented progress toward the implementation of these recommendations at each subsequent IACC meeting.

Section 105: Report to Congress

Section 105 requires the Secretary of HHS to submit an annual report to Congress "concerning the implementation of this title and the amendments made by this title." This seventh annual report reflects HHS activities through October 2006.

View Archives