Abstract
Early detection and intervention are believed to be key to facilitating better outcomes in children with autism, yet the impact of age at treatment start on the outcome is poorly understood. While clinical traits such as language ability have been shown to predict treatment outcome, whether or not and how information at the genomic level can predict treatment outcome is unknown. Leveraging a cohort of toddlers with autism who all received the same standardized intervention at a very young age and provided a blood sample, here we find that very early treatment engagement (i.e., <24 months) leads to greater gains while controlling for time in treatment. Pre-treatment clinical behavioral measures predict 21% of the variance in the rate of skill growth during early intervention. Pre-treatment blood leukocyte gene expression patterns also predict the rate of skill growth, accounting for 13% of the variance in treatment slopes. Results indicated that 295 genes can be prioritized as driving this effect. These treatment-relevant genes highly interact at the protein level, are enriched for differentially histone acetylated genes in autism postmortem cortical tissue, and are normatively highly expressed in a variety of subcortical and cortical areas important for social communication and language development. This work suggests that pre-treatment biological and clinical behavioral characteristics are important for predicting developmental change in the context of early intervention and that individualized pre-treatment biology related to histone acetylation may be key.
Highlights
Detection and intervention in autism spectrum disorder (ASD) are topics of paramount importance because of the enormous potential to capitalize on the brain’s enhanced plasticity during early development as a mechanism to positively impact outcomes [1]
Understanding the ingredients that moderate and predict early intervention treatment response is of the utmost importance, especially given the current state of the field, where there is notably large heterogeneity in how children may respond to treatment [13]
We investigate whether pre-treatment standardized clinical behavioral measures and blood leukocyte gene expression patterns moderate how quickly a child will respond
Summary
Detection and intervention in autism spectrum disorder (ASD) are topics of paramount importance because of the enormous potential to capitalize on the brain’s enhanced plasticity during early development as a mechanism to positively impact outcomes [1]. Linear mixed-effect models were experienced in ASD, with oversight from two doctorate-level clinical psychologists with extensive experience in early behavioral intervention used to examine differences in the aSLP as a function of very early (
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