The goal of the proposed project is to determine how individual variation in brain development from childhood to adulthood is associated with variation in clinical course and outcome in autism. We will achieve this goal in three steps. We will first quantify individual whole and regional brain development from imaging data across six time points collected over 15 years using magnetic resonance imaging (volume, cortical thickness, functional connectivity, white matter microstructure) and concurrent clinical and neuropsychological evaluations. The six time points will include the four time points from our existing 10-year longitudinal study (140 male participants with autism and 75 age-matched typically developing participants) plus two more collected over the next five years by the same multisite interdisciplinary team. These extended cohort sequential longitudinal data will span 3-53 years of age. We will analyze age-period-cohort effects across our wide age range. More data will provide enough power to test existence of linear and curvilinear developmental arcs at individual, cohort, and group levels. We will investigate the specificity to autism by comparison to a reading disorder group. Second, we will identify mediating and modulating factors within brain development that help explain why some individuals continue to have severe autism while others improve. Third, we will analyze associations between longitudinal brain functional development and clinical outcome by evaluating the mechanism by which impairment in long- range connectivity and inhibition may ultimately impact adult prognosis. Finally, we explore how trajectories of late brain development may interact with the loss of secondary school services. Our findings will elucidate how brain changes modulate the severity of core autism symptoms and in the cognitive profile of individuals with the disorder. Understanding the paths of late brain development and the relation between brain maturation and cognitive/behavioral changes is essential to identify biological mechanisms involved and to understand how they interact with contextual factors.

Public Health Relevance

The goal of the research is to determine how variation in brain development and maturation from childhood to mid-adulthood is associated with variation in clinical course and outcome in autism. Autism remains a severely impairing lifelong disorder in most cases. Understanding the longitudinal trajectory of late brain development in autism is essential to identify biological mechanisms involved, find more individualized and clinically relevant predictors of future course, and develop secondary and tertiary preventive interventions to improve outcome.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH080826-07
Application #
9309084
Study Section
Developmental Brain Disorders Study Section (DBD)
Program Officer
Gilotty, Lisa
Project Start
2007-08-01
Project End
2021-04-30
Budget Start
2017-05-01
Budget End
2018-04-30
Support Year
7
Fiscal Year
2017
Total Cost
Indirect Cost
Name
University of Wisconsin Madison
Department
Psychiatry
Type
Schools of Medicine
DUNS #
161202122
City
Madison
State
WI
Country
United States
Zip Code
53715
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