Research on Autism/Autism Spectrum Disorders.

The purpose of this program announcement is to encourage grant applications for research to elucidate the diagnosis, epidemiology, etiology, genetics, treatment, and optimal means of service delivery in relation to autistic disorder ("autism") and autism spectrum disorders. These complex disorders are usually of lifelong duration and affect multiple aspects of development, learning, and adaptation in the community, and thus represent a pressing public health need. The etiologies of these disorders are poorly understood but are thought to include genetic, metabolic, immunologic, and infectious or other environmental influences.

Etiology research involving these disorders requires well-integrated, multidisciplinary, methodologically rigorous scientific approaches and access to a sufficient number of well-characterized patients with these disorders. Basic research into the pathophysiology of autism and autism spectrum disorders, including research on brain mechanisms and genetics, is of special interest. Also of interest are clinical and applied investigations that may lead to the development of diagnostic research instruments, treatments, and intervention strategies.

Areas of interest include but are not limited to 1) epidemiology: development of new screening tools; research on the expression of the full range of autism spectrum disorders; studies on their developmental course; studies that characterize the range of expression within families; research on co-occurring features; and studies to determine risk factors in the etiology of autism, including environmental exposures during pregnancy and early childhood; 2) early identification and diagnosis: key diagnostic features associated with various stages of development; assessment of comorbid features including hyperactivity, attentional dysfunctions, epilepsy, and obsessive-compulsive symptoms; assessment and further differentiation of subtypes of autism spectrum disorders including autism, Asperger disorder, Rett disorder, and childhood disintegrative disorder; and developmental factors relevant to reliable and valid diagnosis; 3) genetic studies: large-scale linkage studies of affected relative pairs or extended pedigrees to identify chromosomal regions harboring disease susceptibility genes; family-based association analysis and other linkage disequilibrium approaches to identify a specific susceptibility gene; high-resolution mapping and positional cloning studies; resolution of locus heterogeneity; analysis of the interaction of autism susceptibility gene(s) with environmental exposures and/or genes responsive to environmental insult; and testing for potential candidate genes; 4) studies of brain mechanisms: studies of brain mechanisms underlying development, regulation, and modulation of behaviors characteristic of autism and autism spectrum disorders, particularly mechanisms involving communication and social interaction; studies of brain mechanisms and biologic factors underlying autistic regression or the loss of previously acquired skills; studies of brain mechanisms involved in the development of abnormal electroencephalograms and epilepsy and studies to clarify the subtypes of seizures and seizure disorders in autism; studies to define the neurobiologic basis of neurologic abnormalities and neuropsychiatric symptoms, including motor stereotypes, gait abnormalities, akinesias, dyskinesias, obsessive-compulsive traits, and the exacerbation of these symptoms, including the role of neuroimmune/autoimmune factors; studies that seek to define basic processing deficits using neuropsychologic and cognitive neuroscience techniques; and studies to develop animal models of brain dysfunction in autism and autism spectrum disorders based on genetic or environmental factors or their interaction.

Also: 5) communication skills: longitudinal developmental studies of behaviors that are precursors to later communication and their emergence in children with autism and autism spectrum disorders; sensory, motor, and social-cognitive impairments that affect interaction and communication; predictors of loss of or regression in expressive language abilities; the nature of severe spoken language deficits when other areas of function (e.g., written language skills) are relatively preserved; and interventions designed to remediate communication and related deficits; 6) cognitive science: developmental studies of relevant behaviors during infancy including attention to social and nonsocial stimuli, affective behavior, gaze, vocalization, imitation, initiative, reciprocity, attachment, play, compliance, and self-recognition, and their emergence in children with autism and autism spectrum disorders; research on the delays and deviations in social behavior and cognition during preschool and middle school, including empathy, receptive social-cognitive deficits, and expressive difficulties; studies leading to more sophisticated tests of higher cognitive functioning, especially in social, communicative, reasoning, and problem-solving areas, as well as tests of basic attentional, emotional, and cognitive deficits that may underlie these deficits or be precursors to them; studies of theory of mind, unconventional verbal behaviors, and the sensory-motor factors involved in relevant social cognition; and the development, validation, and refinement of interventions designed to address deficits in complex social and cognitive abilities or their developmental precursors; 7) psychosocial interventions: studies developing new treatments and studies validating, refining, and comparing approaches to the treatment of autism and autism spectrum disorders, as well as studies that analyze and define the critical features of effective intervention; studies that relate characteristics of individuals or diagnostic subtypes to treatment outcomes; research on relevant contextual factors including physical environments, parent-child and sibling-child relationship factors, and peer-child interactions; and studies addressing generalization or the transfer of learning from one setting to another; and 8) pharmacologic/biologic intervention: studies aimed at developing and testing the efficacy and safety of pharmacologic agents that specifically target the core features of autism and autism spectrum disorders; studies of the efficacy and safety of pharmacologic and combined treatments for the most common and impairing psychopathology associated with autism; new approaches to treatment that build on advances in neuroscience, genetics, immunology, and other neurobiologic fields; focused interventions that test specific theories or hypotheses regarding possible neuropathogenesis; and studies that address the benefits of combined drug and psychosocial interventions.

Applications are to be submitted on the grant application form PHS 398 (rev. 4/98) and will be accepted at the following receipt dates: 1 July 2001 and 1 November 2001. Application kits are available at most institutional offices, of sponsored research and may be obtained from the Division of Extramural Outreach and Information Resources, NIH, 6701 Rockledge Drive, MSC 7910, Bethesda, MD 20892-7910 USA, 301-435-0714, e-mail: [e-mail]. Additional information is available on the Internet at http://grants. nih.gov/grants/guide/pa-files/PA-01-051.html.

Contact: Judith Cooper, Division of Extramural Research, National Institute on Deafness and Other Communication Disorders, Executive Plaza South, Room 400C-11, MSC 7180, Bethesda, MD 20892-7180 USA, 301-496-5061, fax: [phone], e-mail: Judith_Cooper@ nih.gov; Steve Foote, National Institute of Mental Health, NSC, 6100 Executive Boulevard, Room 7204, Bethesda, MD 20857 USA, 301-443-3563, fax: [phone], e-mail: [e-mail]; Marie Bristol-Power, National Institute of Child Health and Human Development, 6100 Executive Boulevard, Room 4B09E, MSC 7510, Bethesda, MD 20892-7510 USA, 301-496-1383, fax: [phone], e-mail: [e-mail]; Deborah Hirtz, National Institute of Neurological Disorders and Stroke, 6001 Executive Boulevard, Bethesda, MD 20892 USA, 301-496-5821, fax: [phone], e-mail: [e-mail]; Cindy P. Lawler, Division of Extramural Research and Training, NIEHS, PO Box 12233, MD EC-23, Research Triangle Park, NC 27709 USA, 919-316-4671, fax: [phone], e-mail: lawler@ niehs.nih.gov. Reference: PA No. PA-01-051