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Molecular Autism
Published in: Molecular Autism 1/2019

Open Access 01-12-2019 | Autism Spectrum Disorder | Research

Deviation from normative brain development is associated with symptom severity in autism spectrum disorder

Authors: Birkan Tunç, Lisa D. Yankowitz, Drew Parker, Jacob A. Alappatt, Juhi Pandey, Robert T. Schultz, Ragini Verma

Published in: Molecular Autism | Issue 1/2019

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Abstract

Background

Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental condition. The degree to which the brain development in ASD deviates from typical brain development, and how this deviation relates to observed behavioral outcomes at the individual level are not well-studied. We hypothesize that the degree of deviation from typical brain development of an individual with ASD would relate to observed symptom severity.

Methods

The developmental changes in anatomical (cortical thickness, surface area, and volume) and diffusion metrics (fractional anisotropy and apparent diffusion coefficient) were compared between a sample of ASD (n = 247) and typically developing children (TDC) (n = 220) aged 6–25. Machine learning was used to predict age (brain age) from these metrics in the TDC sample, to define a normative model of brain development. This model was then used to compute brain age in the ASD sample. The difference between chronological age and brain age was considered a developmental deviation index (DDI), which was then correlated with ASD symptom severity.

Results

Machine learning model trained on all five metrics accurately predicted age in the TDC (r = 0.88) and the ASD (r = 0.85) samples, with dominant contributions to the model from the diffusion metrics. Within the ASD group, the DDI derived from fractional anisotropy was correlated with ASD symptom severity (r = − 0.2), such that individuals with the most advanced brain age showing the lowest severity, and individuals with the most delayed brain age showing the highest severity.

Limitations

This work investigated only linear relationships between five specific brain metrics and only one measure of ASD symptom severity in a limited age range. Reported effect sizes are moderate. Further work is needed to investigate developmental differences in other age ranges, other aspects of behavior, other neurobiological measures, and in an independent sample before results can be clinically applicable.

Conclusions

Findings demonstrate that the degree of deviation from typical brain development relates to ASD symptom severity, partially accounting for the observed heterogeneity in ASD. Our approach enables characterization of each individual with reference to normative brain development and identification of distinct developmental subtypes, facilitating a better understanding of developmental heterogeneity in ASD.
Appendix
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Metadata
Title
Deviation from normative brain development is associated with symptom severity in autism spectrum disorder
Authors
Birkan Tunç
Lisa D. Yankowitz
Drew Parker
Jacob A. Alappatt
Juhi Pandey
Robert T. Schultz
Ragini Verma
Publication date
01-12-2019
Publisher
BioMed Central
Published in
Molecular Autism / Issue 1/2019
Electronic ISSN: 2040-2392
DOI
https://doi.org/10.1186/s13229-019-0301-5

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