Neurophenotypic Trajectories and Behavioral Outcomes in Autism Spectrum Disorder

Investigator: Fumiko Hoeft, MD, PhD
Sponsor: University of California Davis

Location(s): United States


Autism spectrum disorder (ASD) has a common set of diagnostic features that nonetheless vary substantially in severity in different individuals. There are also many co-morbid features ranging from developmental delay to epilepsy to gastrointestinal disturbances that further complicate the phenotypes of ASD. To discover and integrate multilevel phenotypic information that would allow definition of biological subtypes and potentially predict and facilitate optimal outcomes, the MIND Institute initiated the Autism Phenome Project (APP) in 2006. To date, behavioral, medical, immunological and magnetic resonance imaging (MRI) data have been acquired on 279 children (189 ASD, 90 typically developing controls - TD) at 2-3.5 years of age. Of these, 210 (134 ASD, 76 TD) have received a second MRI scan one year later and thus far 142 (83 ASD, 59 TD) have received a third scan at 5-6.5 years of age. This program of research has identified a number of neurophenotypes of ASD related to abnormal amygdala growth and abnormal brain enlargement. But, do these brain differences really matter? An overarching goal of the proposed research is to determine whether identified neural phenotypes persist into middle childhood and are associated with the quality and severity of core and co-morbid behavioral impairments. A unifying hypothesis is that different morphometric patterns will be associated with clinical features and with the quality of behavioral outcome. We are particularly interested in whether there are different patterns of brain organization that may predict optimal behavioral outcomes in ASD. Using recently developed behavioral modification procedures that yield high quality MRI images from children at all severity levels of ASD, we propose to obtain an additional MRI time point and conduct extensive behavioral assessment of children enrolled in the APP when they reach 9-11 years of age. Based on previous return rates, we estimate that 195 children will participate. We will also recruit 100 new subjects into the APP program.

This research would allow an unprecedented exploration of the relationship between brain development, behavioral abnormalities, and cognitive and functional outcome in children transitioning from early to middle childhood. We propose:

1. To evaluate brain and behavioral consequences of three patterns of early amygdala growth;

2. To evaluate brain and behavioral consequences of abnormal brain enlargement in early childhood; and

3. To identify a pattern of brain organization that is associated with optimal behavioral outcome.

These projects are consistent with Objectives 1 and 2 of the NIMH Strategic plan and address the 2009 IACC Strategic Plan crosscutting themes of Heterogeneity and Lifespan Perspective. They also contribute to the still unmet research opportunity for Multi-disciplinary, longitudinal, biobehavioral studies of children, youths, and adults beginning during infancy that characterize neurodevelopmental and medical developmental trajectories across the multiple axes of ASD phenotype.... An important goal is to identify children who will need additional or specialized help to achieve the highest quality of life.