Converging data suggest that autism spectrum disorder (ASD), a neurodevelopmental syndrome characterized by deficits in attention, communication and social interaction, represents a disorder of connectivity, in which the environment may interact with the genome. Recent studies address both microstructural and functional connectivity in ASD populations ranging from preschool through young adulthood and demonstrate both increases and reductions in connectivity in ASD subjects compared to age- matched controls. The frontal, temporal and parietal regions are most affected, and longitudinal studies suggest that ASD alters the trajectory of neural networks in the developing brain, but the systems involved and the timing of these changes are just beginning to be explored. The recent explosive growth in high-resolution imaging now makes the entirety of the developing human fetal brain accessible at the functional level at serial key developmental milestones during gestation, all non-invasively and safe to mother and fetus. Our overarching goal is to identify early MR imaging biomarkers of the impact of high familial risk for ASD on the dynamic functional development of the human fetal brain. Our strategy is to employ advanced static and longitudinal regression and growth curve analyses to identify stress- related changes in sophisticated MRI signals across the 3rd trimester of gestation and associate specific ASD risk-related fetal brain changes to early neurobehavioral signs in neonates. These findings will inform specific targets and timing of future neuroprotective strategies, advance clinical practices, and improve neurobehavioral outcomes.

Public Health Relevance

Converging data suggest that autism spectrum disorder (ASD), a neurodevelopmental syndrome characterized by deficits in attention, communication and social interaction, represents a disorder of connectivity, in which the environment may interact with the genome. There are almost 46,00 children newly diagnosed with ASD each year in the United States, and the long-term medical and educational costs for children with ASD approach $13 billion annually. If successful, this proposal will begin to identify critical fetal neurodevelopmental variables by which high familial risk for ASD influences neonates and their future risk of neuropsychiatric illness.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Specialized Center (P50)
Project #
1P50HD093078-01
Application #
9388745
Study Section
Special Emphasis Panel (ZRG1)
Project Start
Project End
Budget Start
2017-07-01
Budget End
2018-06-30
Support Year
1
Fiscal Year
2017
Total Cost
Indirect Cost
Name
Yale University
Department
Type
DUNS #
043207562
City
New Haven
State
CT
Country
United States
Zip Code
06520