Biennial Report of the Director

Centers of Excellence
Autism Centers of Excellence

Establishment of the Autism Centers of Excellence

CDC’s Autism and Developmental Disabilities Monitoring (ADDM) Network estimates that about 1 in 88 children has an ASD. These estimates are based on data collected from health and special education records of children living in 14 areas of the U.S. during 2008.13 NIH is working to better understand the causes of autism spectrum disorder and develop treatments for this serious and disabling disorder.

To address this public health challenge, Congress passed the Combating Autism Act of 2006, which emphasized the need to expand research and improve coordination among NIH Centers of Excellence focused on autism spectrum disorder. In response to the Combating Autism Act, the NIH Autism Coordinating Committee formed the Autism Centers of Excellence (ACE) program by consolidating the aims of two previous autism spectrum disorder research programs into a single research effort. The previous programs were the Collaborative Programs of Excellence in Autism (CPEA, established in 1997) and Studies to Advance Autism Research and Treatment (STAART, established in 2002 and completed in 2008). The ACE program, funding of which began in FY 2007 and FY 2008, focuses on identifying the causes of autism spectrum disorder and developing new and improved treatments.

13Autism and Developmental Disabilities Monitoring Network (CDC). Prevalence of Autism Spectrum Disorders—Autism and Developmental Disabilities Monitoring Network, 14 Sites, United States 2008. MMWR. 2012/61(SS03);1–19. PMID: 22456193.

How the Autism Centers of Excellence Function within the NIH Framework

A key feature of the Combating Autism Act was expanding the scope of the Interagency Autism Coordinating Committee (IACC), initially established by the Children’s Health Act of 2000. The IACC includes federal agency representatives and members of the public appointed by the Secretary of HHS. In accordance with the 2006 law, and as re-authorized under the Combating Autism Reauthorization Act of 2011, the IACC develops and updates annually a strategic plan for autism spectrum disorder research and a summary of autism spectrum disorder research advances. The first edition of the plan was released in 2009, and annual updates were released in 2010 and 2011. Though the ACE program was initiated prior to completion of the first IACC Strategic Plan, ACE activities address many identified priority areas, including biomarkers, genetic susceptibility, pharmacological treatments, early intervention, and risk and protective factors.

The ACE program comprises five centers and six research networks. ACE centers foster multidisciplinary collaboration among teams of specialists at a single facility to address a particular research question in depth. Each center conducts interdependent sub-projects. ACE networks unite researchers at many different facilities throughout the country; working as a unit, each network addresses a particular research question in depth. Because networks encompass multiple sites, they are able to recruit large numbers of participants with autism spectrum disorder, achieving optimal design for treatment trials.

The goals of the ACE program were established by the NIH ACC—a working group composed of the seven NIH Institutes (NIMH, NICHD, NIDCD, NINDS, NIEHS, NINR, & NCCAM) that support autism spectrum disorder research and are tasked with enhancing the quality, pace, and coordination of research efforts at the NIH in order to find a cure for autism. Five of the ACC ICs provide funding to the ACE program (NIMH, NICHD, NIEHS, NINDS, & NIDCD), and these ICs share administrative and oversight responsibilities.

Description of Disease or Condition

Leo Kanner first described autism in 1943 as a disorder “characterized by extreme aloneness and a desire for the preservation of sameness, with a variety of behavioral (cognitive, affective) symptoms derived from them.”14 Over time, growing recognition of a broader range of related disorders led to the use of the term autism spectrum disorder, which includes several complex neurodevelopmental disorders of early childhood that vary in severity, share common clinical features, and usually persist throughout the lifetime of the individual. Common features include social impairments; verbal and nonverbal communication difficulties; and restricted, repetitive, and stereotyped behavior patterns. “Classic” autistic disorder is the most disabling; other forms of autism spectrum disorder, such as Aspergers disorder, have fewer or milder symptoms. Intellectual disabilities, seizures, and self-abusive behaviors are common among children at the more severe end of the spectrum.

A child’s primary caregivers often are the first to identify autism spectrum disorder symptoms. As early as infancy, a baby with autism spectrum disorder may be unresponsive to people or focus intently on one item to the exclusion of others for long periods. A child with autism spectrum disorder may appear to develop normally and then withdraw and become indifferent to social engagement. Clinicians can make a reliable autism spectrum disorder diagnosis for most children by age three. The current autism spectrum disorder diagnostic criteria and classifications represent progress in identifying a core set of developmental symptoms that, in the past, clinicians might have diagnosed differently because the criteria were more narrowly defined than they are today.

14 Kanner L. Nerv Child. 1943;2:217–50.

Burden of Illness

Autism spectrum disorder causes tremendous economic and social burdens for families and society at large. Although autism spectrum disorder varies greatly in character and severity, it occurs in all ethnic and socioeconomic groups and affects every age group. Currently, no coherent and comprehensive system of care is available for affected individuals. People with autism spectrum disorder might receive private and public services in special education settings, hospitals, university medical centers, or residential treatment facilities, among others.

Some scientists and economists have estimated that the combined direct and indirect costs of providing care for all Americans with autism spectrum disorder during their lifetimes exceed $34 billion. The estimated costs over a lifetime for each person total $3 million.15 Families often incur large debts for medical and education services that public programs or medical insurance do not cover. In addition, autism spectrum disorder often leads to profound emotional hardships for patients and their families. However, the Affordable Care Act will help ease the financial burden that often comes with treating and caring for people with autism spectrum disorder. The law requires new plans to cover autism screening and developmental assessments for children at no cost to parents and allows parents to keep their children on their family health insurance until they turn 26. Insurers will also no longer be allowed to deny children coverage for a pre-existing condition such as autism or to set arbitrary lifetime or annual limits on benefits.

Prevalence estimates—the number of affected individuals at a given point in time—have increased markedly since the early 1990s. CDC currently estimates that as many as 1 in 88 children has autism spectrum disorder.16 Boys are approximately four times as likely as girls are to have autism spectrum disorder. 17 However, it is unclear if incidence, the number of new cases across time in the same population, also has increased. It also is unclear whether the rise in prevalence is due to such factors as the use of different criteria to diagnose autism spectrum disorder, earlier and more accurate autism spectrum disorder diagnoses, or increases in biologic, environmental, or other risk factors. A similar increase in autism spectrum disorder prevalence has occurred in other countries.

15 Ganz ML. Arch Pediatr Adolesc Med. 2007;161(4):343–9. PMID: 17404130.
16 Autism and Developmental Disabilities Monitoring Network. MMWR Surveill Summ. 2012;61(3):1–19. PMID: 22456193.
17 Fombonne E. J Clin Psychiatry. 2005;66 Suppl 10:3–8. PMID: 16401144.

Scope of NIH Activities: Research and Programmatic

The six centers and five networks that compose the ACE program cover a broad range of autism spectrum disorder research areas, including early brain development and functioning, social interactions in infants, rare genetic variants and mutations, associations between autism-related genes and physical traits, possible environmental risk factors and biomarkers, and a potential new treatment.

In an effort to support and accelerate research in the prevention, cause, diagnosis, and treatment of research on autism spectrum disorder, NIH created the National Database for Autism Research (NDAR), an informatics system and central data repository. NDAR collects a wide range of data types, including phenotypic, clinical, and genomic, as well as de-identified medical images, derived from individuals who participate in autism spectrum disorder research, regardless of the source of funding. NDAR provides the infrastructure to store, search across, retrieve, and analyze these varied types of data.

While NDAR receives data from many public and privately funded research sources, all ACE centers and networks are required to contribute their data to NDAR. NDAR also coordinates data access with other federal databases, such as the NIMH Center for Collaborative Genetic Studies. The center is a national resource for researchers who study the genetics of complex mental disorders, including autism spectrum disorder, and stores human DNA, cell cultures, and clinical data. In 2011, NDAR received an HHSinnovates award, recognizing its outstanding efforts to accelerate research within the Department.

NIH Funding for FY 2010 and FY 2011

Five NIH ICs fund the ACE program: NICHD, NIDCD, NIEHS, NIMH, and NINDS. NIH funding for the ACE program, which includes centers (P50s), a cooperative agreement (U01), and networks (R01s), was $25.60 million in FY 2010 and $25.50 million in FY 2011.

FY 2010 and FY 2011 Progress Report

Programmatic and Research Activities and Outcomes

The activities and several accomplishments of the ACE program are highlighted briefly below.

Yale University: Researchers are searching for biomarkers of visual engagement and auditory perception in infants at risk for autism spectrum disorder. Their projects will build upon existing research on the behavioral, brain, and molecular aspects of autism spectrum disorder and may lead to new discoveries on the causes and best treatments for autism spectrum disorder.

University of Illinois at Chicago: Researchers are studying genetic factors as well as brain chemicals and brain functions that could account for repetitive behaviors in people with autism spectrum disorder. They also are testing whether genetic differences influence how individuals respond to certain medications intended to reduce the frequency of these behaviors.

University of Washington: Researchers are investigating genetic and other factors that might increase a person’s risk for autism spectrum disorder and factors that might protect people from developing autism spectrum disorder. Researchers at the University of Washington center conducted a randomized computerized training program for adults with autism spectrum disorder who showed initial impairment in their ability to recognize faces. Their findings suggest that adults with autism spectrum disorder who undergo the computerized training can gain expertise in facial recognition and processing skills.18

University of North Carolina at Chapel Hill: Investigators from the ACE network are studying abnormal processes in early brain development by examining brain images of very young children at risk for developing autism spectrum disorder. A study from the network found evidence of enlarged portions of the amygdala in 6- to 7-year-old children with autism spectrum disorder and that these differences were associated with deficits in social and communicative behavior.19

University of California, San Diego (UCSD): The UCSD ACE is using brain imaging methods to track brain development in children believed to be at risk for autism spectrum disorder. In a recent study, UCSD ACE investigators found that children with autism had 67 percent more neurons in the prefrontal cortex and heavier brains for their age compared to typically developing children. Since these neurons are produced before birth, the study’s findings suggest that differences in prenatal cell birth or maintenance may be involved in the development of autism.20

University of California, Los Angeles: Researchers at the ACE are studying the causes and treatments of social communication problems in people with autism spectrum disorder.

University of Pittsburgh: The University of Pittsburgh ACE is studying how people with autism spectrum disorder learn and understand information.

Drexel University: Researchers with the Drexel University network sites are studying possible risk factors and biological indicators of autism spectrum disorder before and soon after birth. This project is part of the Early Autism Risk Longitudinal Investigation (EARLI).

University of California, Davis: Researchers with the UC-Davis network sites are examining factors that might be useful for improving treatment outcomes in very young children with autism. They are comparing an intensive behavioral intervention to standard community-based treatment.

Wayne State University: Investigators with the Wayne State network sites will conduct a clinical trial to test the safety and efficacy of buspirone, a drug that increases the body’s production of serotonin—one of several neurotransmitters that brain cells use to communicate with each other—as an early intervention in children younger than six years with autism spectrum disorder. A pilot study by the Wayne State researchers showed that buspirone improves social interaction and reduces repetitive behaviors, sensory dysfunction (extreme sensitivity or lack of sensitivity to light, noise, and touch), and anxiety in children with autism.

University of California, Los Angeles: Researchers at the University of California, Los Angeles network sites are studying the relationship between genes related to autism and physical features. They also are investigating rare genetic variations, mutations, and abnormalities that affect a person’s risk for autism.

Several investigators across the ACE centers and networks (University of California – Los Angeles, University of Illinois at Chicago, University of Pittsburgh, University of North Carolina at Chapel Hill, Yale University, and University of Washington), contributed both genetic data and analytic expertise to study the genome-wide characteristics of rare copy number variations or genetic mutations that are strongly associated with the risk of autism spectrum disorder. This large study identified both inherited and de novo (i.e., spontaneous or induced, not inherited) copy number variations that implicated a number of genes associated with risk of the disorder.21

18 Faja S, et al. J Autism Dev Disord. 2012;42(2):278–93. PMID: 21484517.
19 Kim JE, et al. Arch Gen Psychiatry. 2010;67(11):1187–97. PMID: 21041620
20 Courchesne E, et al. JAMA. 2011;306(18):2001–10. PMID: 22068992.
21 Pinto D, et al. Nature. 2010;466(7304):368–72. PMID: 20531469.

Recommendations for Improving the Effectiveness, Efficiency, and Outcomes of the NIMHD COEs

Evaluation Plans

The Combating Autism Act of 2006 and the NIH Reform Act of 2006 require that NIH conduct periodic reviews of the ACE program. To implement this requirement, the NIH formed the Autism Evaluation Implementation Oversight (AEIO) working group, with membership comprising Planning and Evaluation Officers at the five NIH Institutes that provide financial support and scientific expertise to the ACE program (NIMH, NICHD, NINDS, NIEHS, and NIDCD). In 2008-2009, the group initiated a feasibility study to evaluate the ACE program. The objectives of the study were 1) to determine the availability of data and the feasibility of answering key questions about the ACE program, and 2) to obtain baseline data on the ACE program. The key study questions focused on the program’s implementation and scientific scope. This included describing the organization and staffing of the ACE centers and networks, the publication and grant history of the ACE investigators, areas of research addressed in the ACE program, leveraging of additional funding sources, and the role of NDAR in the ACE program. The study also collected data on initial outputs resulting from ACE program research, including research publications and science advances, as well as other information to guide plans for future ACE program evaluation activities. Overall, this initial study and future evaluation activities are intended to complement, but not duplicate, the NIH scientific peer review process, which remains the primary means to ensure the scientific excellence of NIH-funded research.

A report addressing the areas outlined above was developed in 2010. Based on the results of the feasibility study, the AEIO has outlined plans to periodically update the baseline data, including plans to update several elements in 2012.

Future Directions

In 2011, as in the prior year, the NIH ACC convened a two-day meeting at which the investigators presented progress towards the goals of their ACE and exchanged ideas for collaborations. Some sessions addressed data sharing options through the NDAR, with time allotted for a question-and-answer period with NDAR staff. ACE principal investigators and project principal investigators, as well as core directors and data managers, attended. Principal investigators were encouraged to invite K award (career development grant) recipients, fellows, and postdoctoral students from their laboratories.

In FY 2011, NIH re-issued the ACE funding announcements (RFA-HD-12-195; RFA-HD-12-196). Applicants were instructed that highest funding priority would be given to projects related to gaps identified by the 2011 IACC Strategic Plan.

Table 4-6. Autism Centers of Excellence (ACEs)
Institution and Location Year Established
University of California, Davis, CA 2007
University of California, Los Angeles, CA 2007
University of California, San Diego, CA 2007
University of Illinois, Chicago, IL 2007
University of North Carolina, Chapel Hill, NC 2007
University of Pittsburgh, Pittsburgh, PA 2007
University of Washington, Seattle, WA 2007
Yale University, New Haven, CT 2008
Wayne State University, Detroit, MI 2008
University of California, Los Angeles, CA 2008
Drexel University, Philadelphia, PA 2008