Header

UZH-Logo

Maintenance Infos

Atypical Brain Asymmetry in Autism-A Candidate for Clinically Meaningful Stratification


Abstract

BACKGROUND

Autism spectrum disorder ("autism") is a highly heterogeneous neurodevelopmental condition with few effective treatments for core and associated features. To make progress we need to both identify and validate neural markers that help to parse heterogeneity to tailor therapies to specific neurobiological profiles. Atypical hemispheric lateralization is a stable feature across studies in autism, but its potential as a neural stratification marker has not been widely examined.

METHODS

In order to dissect heterogeneity in lateralization in autism, we used the large EU-AIMS (European Autism Interventions-A Multicentre Study for Developing New Medications) Longitudinal European Autism Project dataset comprising 352 individuals with autism and 233 neurotypical control subjects as well as a replication dataset from ABIDE (Autism Brain Imaging Data Exchange) (513 individuals with autism, 691 neurotypical subjects) using a promising approach that moves beyond mean group comparisons. We derived gray matter voxelwise laterality values for each subject and modeled individual deviations from the normative pattern of brain laterality across age using normative modeling.

RESULTS

Individuals with autism had highly individualized patterns of both extreme right- and leftward deviations, particularly in language, motor, and visuospatial regions, associated with symptom severity. Language delay explained most variance in extreme rightward patterns, whereas core autism symptom severity explained most variance in extreme leftward patterns. Follow-up analyses showed that a stepwise pattern emerged, with individuals with autism with language delay showing more pronounced rightward deviations than individuals with autism without language delay.

CONCLUSIONS

Our analyses corroborate the need for novel (dimensional) approaches to delineate the heterogeneous neuroanatomy in autism and indicate that atypical lateralization may constitute a neurophenotype for clinically meaningful stratification in autism.

Abstract

BACKGROUND

Autism spectrum disorder ("autism") is a highly heterogeneous neurodevelopmental condition with few effective treatments for core and associated features. To make progress we need to both identify and validate neural markers that help to parse heterogeneity to tailor therapies to specific neurobiological profiles. Atypical hemispheric lateralization is a stable feature across studies in autism, but its potential as a neural stratification marker has not been widely examined.

METHODS

In order to dissect heterogeneity in lateralization in autism, we used the large EU-AIMS (European Autism Interventions-A Multicentre Study for Developing New Medications) Longitudinal European Autism Project dataset comprising 352 individuals with autism and 233 neurotypical control subjects as well as a replication dataset from ABIDE (Autism Brain Imaging Data Exchange) (513 individuals with autism, 691 neurotypical subjects) using a promising approach that moves beyond mean group comparisons. We derived gray matter voxelwise laterality values for each subject and modeled individual deviations from the normative pattern of brain laterality across age using normative modeling.

RESULTS

Individuals with autism had highly individualized patterns of both extreme right- and leftward deviations, particularly in language, motor, and visuospatial regions, associated with symptom severity. Language delay explained most variance in extreme rightward patterns, whereas core autism symptom severity explained most variance in extreme leftward patterns. Follow-up analyses showed that a stepwise pattern emerged, with individuals with autism with language delay showing more pronounced rightward deviations than individuals with autism without language delay.

CONCLUSIONS

Our analyses corroborate the need for novel (dimensional) approaches to delineate the heterogeneous neuroanatomy in autism and indicate that atypical lateralization may constitute a neurophenotype for clinically meaningful stratification in autism.

Statistics

Citations

Dimensions.ai Metrics

Altmetrics

Downloads

14 downloads since deposited on 16 Dec 2020
14 downloads since 12 months
Detailed statistics

Additional indexing

Contributors:Brandeis, Daniel, et al.
Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Psychiatric University Hospital Zurich > Department of Child and Adolescent Psychiatry
Dewey Decimal Classification:610 Medicine & health
Scopus Subject Areas:Health Sciences > Radiology, Nuclear Medicine and Imaging
Life Sciences > Cognitive Neuroscience
Health Sciences > Neurology (clinical)
Life Sciences > Biological Psychiatry
Language:English
Date:25 August 2020
Deposited On:16 Dec 2020 09:18
Last Modified:17 Dec 2020 21:24
Publisher:Elsevier
ISSN:2451-9022
OA Status:Hybrid
Publisher DOI:https://doi.org/10.1016/j.bpsc.2020.08.008
PubMed ID:33097470

Download

Hybrid Open Access

Download PDF  'Atypical Brain Asymmetry in Autism-A Candidate for Clinically Meaningful Stratification'.
Preview
Content: Published Version
Language: English
Filetype: PDF
Size: 1MB
View at publisher
Licence: Creative Commons: Attribution 4.0 International (CC BY 4.0)