The overall UW ACE theme centers on a comprehensive developmental model of risk, risk processes, symptom emergence, and adaptation in autism spectrum disorder (ASD). According to this model, genetic risk factors influence brain development which leads to risk processes, namely altered patterns of interaction between the child and his/her environment, which further contribute to the abnormal development of neural circuitry and subsequent behavior. Project IV has two aims: (1) We seek to identify early manifestations of abnormal brain development in ASD: that is, variations in brain development that influence risk for the development of ASD. Twelve-month old infant siblings of children with autism, and comparison non-risk infants, will be studied using magnetic resonance imaging (MRI) and magnetic resonance spectroscopic imaging (MRSI), and relationships between brain measures and clinical course and symptom onset will be examined. Early detection of autism via biological risk markers offers the promise of presymptomatic diagnosis and, ultimately, of disease-modifying medications or behavioral intervention that can be used early in the disease process and during the presymptomatic period. (2) We plan to study children entering adolescence in order to identify brain developmental changes that may be related to onset seizure and behavioral decline during the adolescent period. We will conduct MRI and MRSI studies on a sample of 13- 14 yr old adolescents with ASD who have been previously imaged at 3-4 and 6 and 9-10 years of age, and matched comparison samples of children with developmental delay and typical development. This study will allow us to understand the relationship between variations in brain development and longer-term clinical outcome, focusing on adolescent seizure onset and cognitive decline. This project directly addresses goals outlined in the NIH Autism Research Matrix, including (1) identification of biological risk indices for the development of autism and autism-related symptoms in infants, and (2) developmental time course characterized for alterations in brain structures and connections in autism.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Specialized Center (P50)
Project #
1P50HD055782-01
Application #
7292337
Study Section
Special Emphasis Panel (ZHD1-MRG-C (16))
Project Start
2007-08-06
Project End
2012-07-31
Budget Start
2007-08-06
Budget End
2008-07-31
Support Year
1
Fiscal Year
2007
Total Cost
$469,152
Indirect Cost
Name
University of Washington
Department
Type
DUNS #
605799469
City
Seattle
State
WA
Country
United States
Zip Code
98195
Jones, E J H; Dawson, G; Webb, S J (2018) Sensory hypersensitivity predicts enhanced attention capture by faces in the early development of ASD. Dev Cogn Neurosci 29:11-20
Jones, Emily J H; Venema, Kaitlin; Earl, Rachel K et al. (2017) Infant social attention: an endophenotype of ASD-related traits? J Child Psychol Psychiatry 58:270-281
Jones, Emily J H; Dawson, Geraldine; Kelly, Jean et al. (2017) Parent-delivered early intervention in infants at risk for ASD: Effects on electrophysiological and habituation measures of social attention. Autism Res 10:961-972
Charman, Tony; Young, Gregory S; Brian, Jessica et al. (2017) Non-ASD outcomes at 36 months in siblings at familial risk for autism spectrum disorder (ASD): A baby siblings research consortium (BSRC) study. Autism Res 10:169-178
Webb, Sara Jane; Garrison, Michelle M; Bernier, Raphael et al. (2017) Severity of ASD symptoms and their correlation with the presence of copy number variations and exposure to first trimester ultrasound. Autism Res 10:472-484
Zhu, Zuobin; Lu, Xitong; Yuan, Dejian et al. (2017) Close genetic relationships between a spousal pair with autism-affected children and high minor allele content in cases in autism-associated SNPs. Genomics 109:9-15
Messinger, Daniel S; Young, Gregory S; Webb, Sara Jane et al. (2016) Commentary: sex difference differences? A reply to Constantino. Mol Autism 7:31
Jones, E J H; Venema, K; Earl, R et al. (2016) Reduced engagement with social stimuli in 6-month-old infants with later autism spectrum disorder: a longitudinal prospective study of infants at high familial risk. J Neurodev Disord 8:7
Neuhaus, Emily; Jones, Emily J H; Barnes, Karen et al. (2016) The Relationship Between Early Neural Responses to Emotional Faces at Age 3 and Later Autism and Anxiety Symptoms in Adolescents with Autism. J Autism Dev Disord 46:2450-63
Kleinhans, Natalia M; Reiter, Maya A; Neuhaus, Emily et al. (2016) Subregional differences in intrinsic amygdala hyperconnectivity and hypoconnectivity in autism spectrum disorder. Autism Res 9:760-72

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