Mol Psychiatry. 2021 Aug 02; doi: 10.1038/s41380-021-01239-2. Epub 2021 Aug 02.

Pre-treatment clinical and gene expression patterns predict developmental change in early intervention in autism.

Molecular psychiatry

Michael V Lombardo, Elena Maria Busuoli, Laura Schreibman, Aubyn C Stahmer, Tiziano Pramparo, Isotta Landi, Veronica Mandelli, Natasha Bertelsen, Cynthia Carter Barnes, Vahid Gazestani, Linda Lopez, Elizabeth C Bacon, Eric Courchesne, Karen Pierce

PMID: 34341515 DOI: 10.1038/s41380-021-01239-2

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.

© 2021. The Author(s).

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Publication Types

• Journal Article

Grant support

• 755816/ERC_/European Research Council/International
• 755816/EC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 European Research Council (H2020 Excellent Science - European Research Council)
• P50-MH081755/U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH)