TY - JOUR
T1 - Atypical Brain Asymmetry in Autism—A Candidate for Clinically Meaningful Stratification
AU - EU-AIMS Longitudinal European Autism Project Group
AU - Floris, Dorothea L.
AU - Wolfers, Thomas
AU - Zabihi, Mariam
AU - Holz, Nathalie E.
AU - Zwiers, Marcel P.
AU - Charman, Tony
AU - Tillmann, Julian
AU - Ecker, Christine
AU - Dell'Acqua, Flavio
AU - Banaschewski, Tobias
AU - Moessnang, Carolin
AU - Baron-Cohen, Simon
AU - Holt, Rosemary
AU - Durston, Sarah
AU - Loth, Eva
AU - Murphy, Declan G.M.
AU - Marquand, Andre
AU - Buitelaar, Jan K.
AU - Beckmann, Christian F.
AU - Ahmad, Jumana
AU - Ambrosino, Sara
AU - Auyeung, Bonnie
AU - Baumeister, Sarah
AU - Bölte, Sven
AU - Bourgeron, Thomas
AU - Bours, Carsten
AU - Brammer, Michael
AU - Brandeis, Daniel
AU - Brogna, Claudia
AU - de Bruijn, Yvette
AU - Chakrabarti, Bhismadev
AU - Cornelissen, Ineke
AU - Crawley, Daisy
AU - Dumas, Guillaume
AU - Faulkner, Jessica
AU - Frouin, Vincent
AU - Garcés, Pilar
AU - Goyard, David
AU - Ham, Lindsay
AU - Hayward, Hannah
AU - Hipp, Joerg
AU - Johnson, Mark H.
AU - Jones, Emily J.H.
AU - Kundu, Prantik
AU - Lythgoe, David J.
AU - Oakley, Bethany
AU - Ruggeri, Barbara
AU - San José Cáceres, Antonia
AU - Simonoff, Emily
AU - Williams, Steve C.R.
PY - 2020
Y1 - 2020
N2 - 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.
AB - 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.
KW - Autism spectrum disorder
KW - Brain asymmetry
KW - Hemispheric specialization
KW - Heterogeneity
KW - Language delay
KW - Normative modeling
UR - http://www.scopus.com/inward/record.url?scp=85093673855&partnerID=8YFLogxK
U2 - 10.1016/j.bpsc.2020.08.008
DO - 10.1016/j.bpsc.2020.08.008
M3 - Article
AN - SCOPUS:85093673855
SN - 2451-9022
JO - Biological Psychiatry: Cognitive Neuroscience and Neuroimaging
JF - Biological Psychiatry: Cognitive Neuroscience and Neuroimaging
ER -