A voxel-wise assessment of growth differences in infants developing autism spectrum disorder

A Cárdenas-De-La-Parra,J.D Lewis,V.S Fonov,K.N Botteron,R.C Mckinstry,G Gerig,J.R Pruett,S.R Dager,J.T Elison,M.A Styner,A.C Evans,J Piven,D.L Collins

doi:10.1016/j.nicl.2020.102551

Abstract

Autism Spectrum Disorder (ASD) is a phenotypically and etiologically heterogeneous developmental disorder typically diagnosed around 4 years of age. The development of biomarkers to help in earlier, presymptomatic diagnosis could facilitate earlier identification and therefore earlier intervention and may lead to better outcomes, as well as providing information to help better understand the underlying mechanisms of ASD. In this study, magnetic resonance imaging (MRI) scans of infants at high familial risk, from the Infant Brain Imaging Study (IBIS), at 6, 12 and 24 months of age were included in a morphological analysis, fitting a mixed-effects model to Tensor Based Morphometry (TBM) results to obtain voxel-wise growth trajectories. Subjects were grouped by familial risk and clinical diagnosis at 2 years of age. Several regions, including the posterior cingulate gyrus, the cingulum, the fusiform gyrus, and the precentral gyrus, showed a significant effect for the interaction of group and age associated with ASD, either as an increased or a decreased growth rate of the cerebrum. In general, our results showed increased growth rate within white matter with decreased growth rate found mostly in grey matter. Overall, the regions showing increased growth rate were larger and more numerous than those with decreased growth rate. These results detail, at the voxel level, differences in brain growth trajectories in ASD during the first years of life, previously reported in terms of overall brain volume and surface area.

Highlights

Autism Spectrum Disorder (ASD) is a complex neurodevelopmental disorder that is typically diagnosed around 4 years of age (Maenner et al, 2020)
In this study infants were defined as high risk (HR) if they have an older sibling with a community-based, ASD diagnosis confirmed by the Social Communication Questionnaire (SCQ)(Rutter et al, 2003b) and the Autism Diagnostic Interview-Revised (ADI-R)(Rutter et al, 2003a)
Of particular interest to this study are the voxels found to be statistically significant for the interaction between age and group, since it signifies a region that is affected differently by age in each group and may be associated with a group-specific growth trajectory, indicating an increase or decrease in growth rate in the HR+ group compared to the HR- and LRgroups

Summary

Introduction

Autism Spectrum Disorder (ASD) is a complex neurodevelopmental disorder that is typically diagnosed around 4 years of age (Maenner et al, 2020). There continues to be no clear understanding of its underlying causes (Buxbaum and Hof, 2013). ASD is characterized by impaired social communication and interaction, as well as repetitive patterns of behavior, and restricted interests and activities (American Psychiatric Association, 2013) and a characteristic course. Inherent to ASD is the presence of wide phenotypic heterogeneity, which may be one of the factors complicating early identification. A central effort in the field is to improve identification prior to manifestation of behavioral symptoms to facilitate entry into early intervention services (Zwai genbaum et al, 2015).

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