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ARRA Investments in Autism Spectrum Disorders-1

Public Health Burden
Current estimates suggest that around 1 in 100 U.S. children have been diagnosed with an autism spectrum disorder, or ASD. These disorders are associated with a wide range of developmental issues, but the core symptoms are problems with social interactions and communication skills, as well as repetitive and stereotyped behaviors, such as hand flapping or twisting.

Early Detection
Early detection of ASD and intervention can greatly increase a child’s ability to learn new skills and improve overall quality of life. Early detection can also benefit ASD research, as demonstrated by these ARRA grants:
  • A two-site study is adapting the Autism Diagnostic Interview-Revised—the current gold standard for diagnosing autism—into a brief parent interview that can be done over the telephone. This new tool will help reduce research screening costs and help researchers to quickly identify potential participants for ASD studies.1
  • One project is using brain imaging to identify changes in infant brain structure and connectivity that may be early indicators of autism. Additional assessments of behavioral markers will significantly add to efforts to detect ASD at the earliest stages, which will allow earlier interventions to reduce lifelong disability.2
Possible Causes
The exact causes of ASD are still unknown, but research suggests that both a person’s genes and environment play a role. A number of ARRA funded studies will use advanced DNA sequencing technology that allows researchers to quickly study many genes at a time, while others will focus on a variety of other potential causes. For example:
  • One study is exploring the role of infection during pregnancy on raising risk of ASD in a mouse model. Research suggests that a mother’s immune response to infection may affect levels of immune molecules in the fetal brain, impacting brain development and possibly contributing to autism. This study will explore this possible link and may reveal new targets for treating ASD.3
  • A five-site collaborative network of large-scale DNA sequencing centers is assessing their combined study populations to provide unique insights on the biological roots of the disorder and reveal genes and pathways representing high priority targets for developing novel treatments.4
  • Another grant is focused on enhancing the Autism Genetic Resource Exchange (AGRE) database infrastructure so it can link to the National Database for Autism Research (NDAR), broadening access to comprehensive autism datasets and encouraging greater collaboration among ASD researchers.5
  • Some forms of ASD may be associated with defects in the function of mitochondria, components of cells critical for energy production. To better understand this relationship, an ARRA-funded study will search for mutations in mitochondrial genes and characterize mitochondrial defects in people with ASDs.6
Reports of increasing ASD prevalence present an urgent public health concern. As teens with ASD become adults, their health care and service needs change. Diverse populations affected by ASD may face additional issues specific to their culture, socioeconomic status, or access to care; and many professionals who provide ASD-related care and services need better training opportunities. Some ARRA funded projects that address these issues include:
  • A study exploring age-related changes in cognition and possible protective factors, as well as the changing service needs and quality of life concerns among adults and older people with ASD, which may reveal targets for intervention and inform public policy.7
  • A study focusing on how race, gender, socio-economic status, family culture, and communication during clinical encounters affect the health care experiences of African American children with ASD in an urban setting. Such research may help reduce the existing disparities in ASD diagnosis and service delivery for this and possibly other underserved populations.8
  • A project evaluating the effects of three types of professional development models on student and teacher outcomes, addressing the need to improve school-based services for children with autism.9
  • Another project testing the efficacy of an employment program designed to help teens and young adults with autism learn important skills necessary for holding a job.10
  • A project exploring whether a small molecule compound can mimic the actions of a natural brain protein that is deficient in animal models of Rett syndrome, a rare ASD. If effective, this compound may be useful as a new type of treatment for Rett syndrome and similar disorders.11
Disease mechanisms:
Although recognized as neurodevelopmental disorders, much remains unknown about the biological mechanisms underlying ASD and how they disrupt brain development and lead to clinical features. ARRA-funded research to better understand these mechanisms may inform new treatment strategies.
  • A number of ASD-associated genes encode proteins involved in the function of synapses, the communication points between neurons. Two ARRA-funded studies in mouse models focus on such proteins and their interactions in shared cellular pathways, which may suggest disease mechanisms common across ASDs, as well as broadly applicable treatment targets.12,13

  1. 1R01MH089390-01 -- 1/2 Development of a Screening Interview for Research in Autism Spectrum Disorders -- Lord, Catherine (MI)
  2. 3R01MH068398-06A1S1 -- Infants at Risk of Autism: A Longitudinal Study -- Ozonoff, Sally (CA)
  3. 1R01MH088879-01 -- Maternal immune activation, cytokines, and the pathogenesis of autism -- McAllister, A Kimberley (CA)
  4. 1R01MH089175-01, -- 1/5: Elucidating the Genetic Architecture of Autism by Deep Genomic Sequencing -- Gibbs, Richard A (TX); 1 R01 MH089208-01 -- 2/5: Elucidating the Genetic Architecture of Autism by Deep Genomic Sequencing -- Daly, Mark J (MA); 1 R01 MH089025-01 -- 3/5: Elucidating the Genetic Architecture of Autism by Deep Genomic Sequencing -- Buxbaum, Joseph D (NY); 1 R01 MH089004-01 -- 4/5: Elucidating the Genetic Architecture of Autism by Deep Genomic Sequencing -- Schellenberg, Gerard David (PA); 1 R01 MH089482-01 -- 5/5: Elucidating the Genetic Architecture of Autism by Deep Genomic Sequencing -- Sutcliffe, James S (TN)
  5. 1RC1MH089707-01 -- Linking Data Sources from the Autism Genetic Resource Exchange (AGRE) with NDAR -- Lajonchere, Clara M (NY)
  6. 1R01NS070298-01 -- A Mitochondrial Etiology of Autism -- Wallace, Douglas C (CA)
  7. 1R21MH089645-01 -- Autism in the second half of the lifespan: Behavior, daily living, service needs -- Carper, Ruth (CA)
  8. 1R01MH089474-01 -- Autism in urban context: linking heterogeneity with health and service disparities -- Solomon, Olga (CA)
  9. 1RC1MH089760-01 -- Randomized Study of Training in Autism -- Ruble, Lisa A (KY)
  10. 1RC1MH088812-01 -- JobTips: An Employment Preparation Program for Adolescents and Young Adults with ASD -- Strickland, Dorothy Cay (NC)
  11. 1R21MH089518-01 -- TrkB Agonist(s), a Potential Therapy for Autism Spectrum Disorders -- Sun, Yi Eve (CA)
  12. 1R01NS070301-01 -- Dynamic regulation of Shank3 and ASD -- Worley, Paul F (MD)
  13. 1R01NS070302-01 -- Elucidating the Roles of SHANK3 and FXR in the Autism Interactome -- Zoghbi, Huda Y (TX)

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