This program project aims to discover the biological bases of and environmental influences on the social communication deficits in autism. The first two projects propose experimental interventions and longitudinal follow-ups to test the extent to which joint attention, symbolic play, and language can be modified. Based on results showing that particular caregiver behaviors lead to gains in language skills over a 15-year period of development, Project I will test an experimental approach to modifying caregiver behaviors and measuring the consequences. Project II will follow a group of children whose nonverbal communication and play skills were improved through intervention, and will also attempt to generalize the intervention from skilled clinicians to paraprofessionals with a new sample of children. In order to understand the basis for the deficits associated with autism, Project III aims to explicate the role that duplication of chromosome 15q plays in autism by assessing the phenotypic sequelae in probands with known duplications. The proposed project also plans to define the autism critical region by detailed examination of rearrangements in probands with unusual breakpoints or imprinting errors. Lastly, the extent of cryptic duplication in the population of idiopathic autism will be investigated with newly developed mapping techniques. Project IV focuses on the neuroanatomical bases of social communication deficits in autism. The proposed project will use fMRI to investigate fundamental aspects of information processing: imitation, joint attention, and referencing. These studies will test the hypothesis that deficits in the response properties of specific neural populations, such as mirror neurons, and deficits in the brain's reward systems underlie impairments in perception of referencing and joint attention, which give rise to the social communication deficits in autism.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Program--Cooperative Agreements (U19)
Project #
5U19HD035470-07
Application #
6663883
Study Section
Special Emphasis Panel (ZHD1-MRG-C (10))
Program Officer
Kau, Alice S
Project Start
1997-06-01
Project End
2007-05-31
Budget Start
2003-06-01
Budget End
2004-05-31
Support Year
7
Fiscal Year
2003
Total Cost
$916,833
Indirect Cost
Name
University of California Los Angeles
Department
Pediatrics
Type
Schools of Medicine
DUNS #
092530369
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
Wegiel, Jerzy; Flory, Michael; Schanen, N Carolyn et al. (2015) Significant neuronal soma volume deficit in the limbic system in subjects with 15q11.2-q13 duplications. Acta Neuropathol Commun 3:63
Freeman, Stephanny F N; Gulsrud, Amanda; Kasari, Connie (2015) Brief Report: Linking Early Joint Attention and Play Abilities to Later Reports of Friendships for Children with ASD. J Autism Dev Disord 45:2259-66
Gulsrud, Amanda C; Hellemann, Gerhard S; Freeman, Stephanny F N et al. (2014) Two to ten years: developmental trajectories of joint attention in children with ASD who received targeted social communication interventions. Autism Res 7:207-15
Weintraub, William S; Mandel, Leonid; Weiss, Sandra A (2013) Antiplatelet therapy in patients undergoing percutaneous coronary intervention: economic considerations. Pharmacoeconomics 31:959-70
Siller, Michael; Hutman, Ted; Sigman, Marian (2013) A parent-mediated intervention to increase responsive parental behaviors and child communication in children with ASD: a randomized clinical trial. J Autism Dev Disord 43:540-55
Wegiel, Jerzy; Schanen, N Carolyn; Cook, Edwin H et al. (2012) Differences between the pattern of developmental abnormalities in autism associated with duplications 15q11.2-q13 and idiopathic autism. J Neuropathol Exp Neurol 71:382-97
Wegiel, Jerzy; Frackowiak, Janusz; Mazur-Kolecka, Bozena et al. (2012) Abnormal intracellular accumulation and extracellular A? deposition in idiopathic and Dup15q11.2-q13 autism spectrum disorders. PLoS One 7:e35414
Hogart, A; Leung, K N; Wang, N J et al. (2009) Chromosome 15q11-13 duplication syndrome brain reveals epigenetic alterations in gene expression not predicted from copy number. J Med Genet 46:86-93
Wang, Nicholas J; Parokonny, Alexander S; Thatcher, Karen N et al. (2008) Multiple forms of atypical rearrangements generating supernumerary derivative chromosome 15. BMC Genet 9:2
Bookheimer, Susan Y; Wang, A Ting; Scott, Ashley et al. (2008) Frontal contributions to face processing differences in autism: evidence from fMRI of inverted face processing. J Int Neuropsychol Soc 14:922-32

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