Mr. Chairman, I am Dr. Deborah Hirtz of the National Institute of Neurological Disorders and Stroke (NINDS) at the National Institutes of Health (NIH). I have been asked to appear before you today to give the Committee and the families of autistic individuals a sense of the NIH's ongoing and planned research and other activities related to autism. As a representative of the NIH, and more directly, of the member institutes of the NIH Autism Coordinating Committee, I want to explain that we share the sense of urgency that autistic individuals and their families and advocates feel with regard to unlocking the mysteries of this devastating disorder. I will try to convey to you the strong commitment of the NIH to increasing our knowledge about autism - what causes it, how best to diagnose and treat it, and we hope not too far in the future, perhaps even how to prevent this dread disorder.
CHARACTERISTICS OF AUTISM
Autism is a complex, life-long, developmental disability that results in difficulty with social interactions, problems in communication, and restrictive or repetitive interests and behaviors. There is considerable variability in the severity of the symptoms, and intellectual function can range from profound mental retardation to above average performance on IQ tests. Epilepsy also occurs in about 30 percent of autistic individuals. Approximately 20 percent of children with autism reportedly experience a "regression;" that is, they have apparently normal early development, but then lose their ability to communicate and lose their social skills, usually sometime in the second year of life. Boys are three-to-four times more likely to be affected by autism than girls. Autism occurs in all racial, ethnic, and social groups.
NIH AUTISM COORDINATING COMMITTEE
I would like to briefly discuss the role of the NIH Autism Coordinating Committee (NIH/ACC). The NIH/ACC was established in response to a 1996 Congressional request that NIH establish a mechanism to coordinate its autism research activities and assure the most effective use of its resources. Its members include the Directors of the National Institute of Child Health and Human Development (NICHD), the National Institute of Mental Health (NIMH), the National Institute on Deafness and Other Communication Disorders (NIDCD), and the NINDS, as well as the program staff who manage the autism research portfolios of these institutes. The committee was recently expanded to include advisory representatives from the National Institute of Environmental Health Sciences (NIEHS), National Institute of Allergy and Infectious Diseases (NIAID), and the National Center for Complementary and Alternative Medicine (NCCAM). Representatives from the Food and Drug Administration, the Centers for Disease Control and Prevention (CDC), and the U.S. Department of Education have also been invited to participate in specific topic-focused meetings of the NIH/ACC. The full committee meets at least three times a year to coincide with meetings of the institute national advisory councils, and meets annually with representatives of autism research advocacy organizations.
NIH AUTISM RESEARCH
NIH supports research on brain anatomy and development in autism, language impairment, co-morbid conditions such as epilepsy, and attentionality and behavior, as well as possible genetic causes and mechanisms. Over the last five years, the total NIH funding for autism research has nearly quadrupled—from $10.5 million in Fiscal Year 1995 to $40 million in Fiscal Year 1999.
Unfortunately, we do not have a definitive answer to the question of what the true incidence of autism is. Estimates vary widely, but recent studies suggest that as many as one in 500 persons may be affected by some form of autism. Recent reports suggest that the incidence of autism may be substantially increasing. It is not clear that the reported increases can be accounted for by improved or expanded diagnosis, or by the increasing availability of educational and other support services, although these are surely factors. Appropriate large-scale studies, though time-intensive and expensive, must be done in order to develop definitive estimates of incidence. NIH recognizes the pressing need to do the work that will give us essential knowledge of the true prevalence of autism and the trends of that prevalence over time, and is actively working with the CDC to design studies that could yield this knowledge.
SCREENING AND DIAGNOSIS
Accurate and consistent early diagnosis of autism is difficult. To address this problem and in response to the requests of concerned parents, the NIH/ACC institutes, working with the American Academy of Neurology, sponsored a 1998 conference on the State of the Science in Autism: Screening and Diagnosis. The conference included representatives of 12 major medical and other professional academies and societies, six parent advocacy groups, and representatives of the CDC and U.S. Department of Education. Attendees reviewed the existing research evidence for autism screening and diagnosis criteria. Current evidence suggests that symptoms of autism are measurable by 18 months of age, and autism can be reliably diagnosed by or before age three. Parents and expert clinicians can often detect symptoms during infancy, although a formal diagnosis is generally not made until the child fails to develop functional language by age two or later. Research is seeking to determine whether studies of home video observations of subtle motor and social behaviors may lead to behavioral diagnosis in the first year.
This research review became the evidence base for a subsequent meeting in January 1999, sponsored by the Child Neurology Society and the American Academy of Neurology. Based on the assembled research evidence, a consensus statement is being developed as a practice parameter, which is a professional guideline for recommended procedures, criteria, and timing for screening and diagnosis in autism. This will the first time that such a multidisciplinary group has reached consensus on screening and diagnostic procedures in autism. A summary of the literature review was published in a special issue on diagnosis in the Journal of Autism and Developmental Disorders (JADD), Vol. 29, (6), 1999, pp. 439-484). The specific practice parameter or clinical recommendations, once approved by the Boards of the professional societies, will be published in Neurology, and the Journal of Child and Adolescent Psychiatry, and are also expected to be published in each of the other professional journals representing medical or professional specialties that participated in the meetings. In endorsing these clinical guidelines, each of the participating organizations officially adopts these recommendations as the standard for autism screening and diagnosis.
Autism is not a disease, but rather a disorder in which there may be a number of different causal pathways. In the vast majority of cases, no specific underlying cause of autism can be identified. A variety of genetic, metabolic, infectious, and environmental factors may be important. A working group convened by NIH in 1995 reached a consensus that, for at least a significant subgroup of persons with autism, there appears to be a genetic susceptibility that most likely involves multiple genes. To date, genetic causes for Fragile X, the most common genetically inherited form of mental retardation that in some children produces many of the same behaviors and symptoms as autism, and the gene for Rett Syndrome, an autism-spectrum disorder, have been identified. In addition, genetic "hotspots," that is, potential chromosomal locations, for more classic forms of autism have been identified. NIH has conducted two major meetings on the genetics of autism, and supported an international meeting last month to develop plans to combine autism genotyping information being developed in centers around the world. NINDS, NICHD and NIMH are supporting a major pediatric brain imaging initiative to learn how the brain develops in normal infants, children, and adolescents which will provide potential control data for studies of developmental disorders such as autism. A data sharing plan will be implemented to make this resource available to the medical and research communities. However, much remains to be done. This includes more research into molecular genetics, normal immune system development, and the "regression" that occurs in some cases of autism. The NICHD- and NIDCD-funded network of Collaborative Programs of Excellence in Autism, in collaboration with CDC, is planning to launch a series of studies of persons diagnosed with autism who regressed after apparently normal development, as well as matched comparison groups, which should yield valuable insights into potential risk factors and causes of autism.
Although there is currently no known cure, nor treatment which can reverse all the symptoms of autism, interventions designed to alleviate specific symptoms are available. The best-studied therapies include educational, behavioral, and pharmacological interventions, and many children who receive intensive, individualized, behavioral interventions show progress in social and language skills.
In November 1999, NIH held a workshop in conjunction with the Department of Education on "Treatments for People with Autism and Other Pervasive Developmental Disorders: Research Perspectives" to evaluate the current biological, behavioral, psychopharmacological, and biomedical treatments in autism, and to identify critical research needs in autism treatment. The written reports and recommendations from the working groups at this meeting have only recently been assembled, and are currently being reviewed by the members of the NIH/ACC and representatives of autism advocacy groups to consider the next steps for incorporating these into the NIH autism research agenda.
Six rapid-turnaround, multi-site, double blind, placebo-controlled studies of secretin have been supported through the NICHD- and NIDCD-funded Collaborative Programs of Excellence in Autism. The results of one study have already been published in the New England Journal of Medicine, and the others are expected to be completed and published in the near future. In addition, NIMH-supported Research Units in Pediatric Psycho-pharmacology are conducting studies of risperidone, a drug which is used to treat autism.
The NIH/ACC institutes have conducted or supported a number of other activities related to autism research:
- Issuing a joint Program Announcement to solicit and encourage grant applications for research designed to increase our knowledge of the diagnosis, epidemiology, causes, genetics, and treatment of autism and autism spectrum disorders;
- Developing an overall autism information dissemination plan by the NIH/ACC public information officers, with input from the national autism parent organizations, to reach broader parent and health professional audiences, particularly with regard to research validated procedures for autism early screening and diagnosis;
- Conducting a workshop entitled "Building Animal Models for Autism Through Translational Neuroscience Research;"
- Supporting the creation of the Autism Tissue Program and its outreach activities under the auspices of the National Alliance for Autism Research and the Autism Society of America, and supporting inclusion of autism materials by other NIH-funded brain and tissue Banks across the country;
- Initiating the planning of a pilot study for a large-scale, longitudinal, multi-agency, multi-institute, prospective, population-based study to establish or rule out causal links between a variety of environmental events and normal or abnormal development, including autism. If funded, this would be the largest prospective study ever undertaken, and would take several years to design and pilot study, before the full-scale study could be undertaken.
I have very briefly described some of the NIH autism research activities. Autism research is a major priority for the NIH. We clearly recognize that much remains to be accomplished, and we are committed to continuing to work to expand our efforts.
Mr. Chairman, this concludes my prepared statement. I would be pleased to respond to questions you and the members of the Committee may have.