Pre-treatment clinical behavioral and blood leukocyte gene expression patterns predict rate of change in response to early intervention in autism

Abstract

AbstractEarly 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 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 predicts 21% of the variance in the rate of skill growth during early intervention. Pre-treatment blood leukocyte gene expression patterns also predicts rate of skill growth, accounting for 13% of the variance 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 post-mortem cortical tissue, and are normatively highly expressed in variety of subcortical and cortical areas important for social-communication and language development. This work indicates for the first time that gene expression can predict the rate of early intervention response and that a key biological factor linked to treatment outcome could be the susceptibility for epigenetic change via mechanisms such as histone acetylation.