Stratifying the Heterogeneity of Autism Spectrum Disorder: Impact of Co-Occurring Anxiety and ADHD

ABSTRACT
The substantial heterogeneity in autism spectrum disorder (ASD) is a key barrier in early diagnosis and in developing
and evaluating effective treatments for the disorder. Although early behavioral intervention targeting social,
cognitive, and adaptive functioning improves outcomes for many children with ASD, there is significant variability in
treatment response within studies. Given this variation, stratifying the heterogeneity of ASD is essential for identifying
biomarkers to help providers systematically diagnose, tailor treatment, and monitor response. The proposed project
responds to this critical need by elucidating the impact of a potential key source of this heterogeneity: co-occurring
anxiety and ADHD. Little is known about the unique and additive impacts of co-occurring anxiety and ADHD on
individuals with autism in the early childhood period. Furthermore, the impact of these co-occurring disorders on
commonly used neural and behavioral biomarkers remains a gap in the current literature. To fill these gaps in the
literature, we propose a multimodal approach, using a combination of parent reports, observational assessments,
and neurophysiological assays, to carefully phenotype samples of young children from 4 groups: ASD alone,
ASD+Anxiety, ASD+ADHD, and ASD+Anxiety+ADHD. Our central hypothesis is that co-occurring anxiety or ADHD
will have both unique and additive effects on the clinical presentation, executive functioning, and biomarker
signatures of young children with ASD. To test this hypothesis, we have three aims: (1) Differentiate the impact of
co-occurring anxiety or ADHD on core and associated symptoms in young children with ASD. (2) Identify the
relationship between co-occurring anxiety or ADHD and executive function deficits in young children with ASD. (3)
Determine the relationship between co-occurring anxiety or ADHD and neural, attentional, and behavioral
biomarkers being used to characterize and monitor treatments in ASD. If successful, this project will provide a better
understanding of the impact of co-occurring ADHD and anxiety on the clinical presentation, functional outcomes,
and neurobiology of ASD. This in turn will improve our ability to stratify young children with ASD into meaningful
subgroups. This knowledge will support development of effective and biologically informed methods for early
detection and treatment, which can mitigate the negative effects of co-occurring ADHD and anxiety on long-term
outcomes of individuals with ASD.

Grant Number: 5R01HD101440-05
NIH Institute/Center: NIH
Principal Investigator: Kimberly Carpenter