A Longitudinal MRI Study of Infants at Risk for Autism

Univ Of North Carolina Chapel Hill, Chapel Hill NC

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Abstract

[unreadable] DESCRIPTION (provided by applicant): Multiple lines of converging evidence (MRI, postmortem, head circumference) document brain enlargement in autism. MRI studies have revealed generalized enlargement in cerebral cortical gray and white matter and selected subcortical structures by age two years. Longitudinal head circumference studies suggest the onset of brain overgrowth in the latter part of the first year. Behavioral studies of high risk (for autism spectrum disorder, or ASD) infant siblings of autistic individuals suggest that the defining features of ASD are not present at six months and first appear by 12 months. This application is a request for supplementary support of an Autism Centers of Excellence (ACE) Network entitled, "A Longitudinal MRI Study of Infants at Risk for Autism" (funded July 2007) which includes four clinical data collection sites (UNC, U Wash, CHOP, Wash U) and a Data Coordinating Center (DCC) (MNI). The original application provided funding to do neuroimaging and behavior assessment on 544 high risk (for ASD) infant sibs at six months and to follow longitudinally only a subset of the most symptomatic at-risk infants at 12 months and, at 24 months, to assess only those high risk infant sibs with ASD (total = 685 scans). By following this subset only (and typically-developing or TYP controls), the investigators will be able to address several important hypotheses about the trajectory of early postnatal brain overgrowth (regions, tissues, structures, and fiber tracts) in autism, as measured on MRI and DTI, and its potential relationship to clinical features. However, by excluding asymptomatic high risk sibs at 12 months and those who do not quite meet ASD criteria at 24 months, the investigators will be limiting the scientific questions that can be addressed in this unique study (e.g., whether brain changes are specific to ASD or they also occur in non-ASD sibs with genetic liability for ASD; to what extent subthreshold ASD features at 12 and 24 months, or a later onset (than 12 months as stipulated in the design of the parent program) of early ASD markers are associated with brain changes seen in autistic disorder). Thus, the overarching goal of this supplement is to collect longitudinal behavioral and neuroimaging data on all high risk infant siblings entering the ACE Network. This supplement specifically requests funding to support longitudinal data collection on high risk sibs who enter the study at six months, but are excluded from further participation in the parent project, at 12 months (N=201 scans) or 24 months (N=194 scans), for symptoms that are below criteria for continued inclusion. By longitudinally studying the entire sample of high risk sibs (from six to 24 months), the investigators will be able to identify behavioral, familial, and neurobiological features that characterize infants who develop an ASD across a range of symptom severity. In this way, they will take full advantage of this unique and important ACE Baby Sibs Imaging Network resource to substantially expand the research questions that can be posed regarding early brain and behavior development in ASD. [unreadable] [unreadable] [unreadable]