Familial risk of autism alters subcortical and cerebellar brain anatomy in infants and predicts the emergence of repetitive behaviors in early childhood

Abstract

Autism spectrum disorder (ASD) is a common neurodevelopmental condition, and infant siblings of children with ASD are at a higher risk of developing autistic traits or an ASD diagnosis, when compared to those with typically developing siblings. Reports of differences in brain anatomy and function in high‐risk infants which predict later autistic behaviors are emerging, but although cerebellar and subcortical brain regions have been frequently implicated in ASD, no high‐risk study has examined these regions. Therefore, in this study, we compared regional MRI volumes across the whole brain in 4–6‐month‐old infants with (high‐risk, n = 24) and without (low‐risk, n = 26) a sibling with ASD. Within the high‐risk group, we also examined whether any regional differences observed were associated with autistic behaviors at 36 months. We found that high‐risk infants had significantly larger cerebellar and subcortical volumes at 4–6‐months of age, relative to low‐risk infants; and that larger volumes in high‐risk infants were linked to more repetitive behaviors at 36 months. Our preliminary observations require replication in longitudinal studies of larger samples. If correct, they suggest that the early subcortex and cerebellum volumes may be predictive biomarkers for childhood repetitive behaviors. Autism Res 2019, 12: 614–627 . © 2019 The Authors. Autism Research published by International Society for Autism Research published byWiley Periodicals, Inc. Lay Summary Individuals with a family history of autism spectrum disorder (ASD) are at risk of ASD and related developmental difficulties. This study revealed that 4–6‐month‐old infants at high‐risk of ASD have larger cerebellum and subcortical volumes than low‐risk infants, and that larger volumes in high‐risk infants are associated with more repetitive behaviors in childhood.

Emerging behavioral and neuroimaging biomarkers for early and accurate characterization of autism spectrum disorders: a systematic review

“…Hippocampus is responsible for memory; and amygdala for the regulation of emotions. The amygdala is relatively enlarged in ASD compared to healthy controls by 2 years of age while demonstrating a growth regression in magnitude between 2 and 4 years of age 65 . The amygdala volume in 2–5-year-old pre-school children with ASD has reported significantly larger than age-matched typically developing children.…”

The Value of Brain Imaging and Electrophysiological Testing for Early Screening of Autism Spectrum Disorder: A Systematic Review

“…More recent research builds upon the findings from Hazlett et al (2017) and delineates significant relationships between abnormal brain volumes and ASD symptomology. Infants between 4 and 6 months old were found to have significantly larger cerebellar and subcortical volumes, which were associated with core repetitive behaviors at 36 months (Pote et al, 2019). Subcortical volumes at 12 months have been associated with language skills at 24 months (Swanson et al, 2017).…”

The Neurodevelopment of Autism from Infancy Through Toddlerhood

“…In a study of boys ages 18 to 42 months, several subcortical structures were found to have increased volume compared to typically-developing controls including the amygdala (20% larger), caudate nucleus, globus pallidus, and putamen 66 . More recently, Qui and colleagues 67 reported bilateral caudate enlargement from 2 to 4 years of age compared to children with developmental delay, and Pote and colleagues reported an overall enlargement of subcortical regions in 4-to 6-month-old infants at high familial risk for ASD (including infants who did and did not develop ASD, n = 26 total, n = 4 with ASD), with greater volumes associated with increased restricted and repetitive behaviors at 36 months 68 . A study of infants at elevated familial risk for ASD found differential associations between amygdala, thalamus, and caudate volumes at age 1 and language abilities at age 2 in infants who were later diagnosed with ASD versus those with language delay only 69 , the authors suggest this is reflective of distinct neural mechanisms, and likely genetic and environmental risk factors, governing language development in infants with ASD.…”