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Dissecting the Heterogeneous Cortical Anatomy of Autism Spectrum Disorder Using Normative Models

BACKGROUND: The neuroanatomical basis of autism spectrum disorder (ASD) has remained elusive, mostly owing to high biological and clinical heterogeneity among diagnosed individuals. Despite considerable effort toward understanding ASD using neuroimaging biomarkers, heterogeneity remains a barrier, p...

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Autores principales: Zabihi, Mariam, Oldehinkel, Marianne, Wolfers, Thomas, Frouin, Vincent, Goyard, David, Loth, Eva, Charman, Tony, Tillmann, Julian, Banaschewski, Tobias, Dumas, Guillaume, Holt, Rosemary, Baron-Cohen, Simon, Durston, Sarah, Bölte, Sven, Murphy, Declan, Ecker, Christine, Buitelaar, Jan K., Beckmann, Christian F., Marquand, Andre F.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier, Inc 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6551348/
https://www.ncbi.nlm.nih.gov/pubmed/30799285
http://dx.doi.org/10.1016/j.bpsc.2018.11.013
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author Zabihi, Mariam
Oldehinkel, Marianne
Wolfers, Thomas
Frouin, Vincent
Goyard, David
Loth, Eva
Charman, Tony
Tillmann, Julian
Banaschewski, Tobias
Dumas, Guillaume
Holt, Rosemary
Baron-Cohen, Simon
Durston, Sarah
Bölte, Sven
Murphy, Declan
Ecker, Christine
Buitelaar, Jan K.
Beckmann, Christian F.
Marquand, Andre F.
author_facet Zabihi, Mariam
Oldehinkel, Marianne
Wolfers, Thomas
Frouin, Vincent
Goyard, David
Loth, Eva
Charman, Tony
Tillmann, Julian
Banaschewski, Tobias
Dumas, Guillaume
Holt, Rosemary
Baron-Cohen, Simon
Durston, Sarah
Bölte, Sven
Murphy, Declan
Ecker, Christine
Buitelaar, Jan K.
Beckmann, Christian F.
Marquand, Andre F.
author_sort Zabihi, Mariam
collection PubMed
description BACKGROUND: The neuroanatomical basis of autism spectrum disorder (ASD) has remained elusive, mostly owing to high biological and clinical heterogeneity among diagnosed individuals. Despite considerable effort toward understanding ASD using neuroimaging biomarkers, heterogeneity remains a barrier, partly because studies mostly employ case-control approaches, which assume that the clinical group is homogeneous. METHODS: Here, we used an innovative normative modeling approach to parse biological heterogeneity in ASD. We aimed to dissect the neuroanatomy of ASD by mapping the deviations from a typical pattern of neuroanatomical development at the level of the individual and to show the necessity to look beyond the case-control paradigm to understand the neurobiology of ASD. We first estimated a vertexwise normative model of cortical thickness development using Gaussian process regression, then mapped the deviation of each participant from the typical pattern. For this, we employed a heterogeneous cross-sectional sample of 206 typically developing individuals (127 males) and 321 individuals with ASD (232 males) (6–31 years of age). RESULTS: We found few case-control differences, but the ASD cohort showed highly individualized patterns of deviations in cortical thickness that were widespread across the brain. These deviations correlated with severity of repetitive behaviors and social communicative symptoms, although only repetitive behaviors survived corrections for multiple testing. CONCLUSIONS: Our results 1) reinforce the notion that individuals with ASD show distinct, highly individualized trajectories of brain development and 2) show that by focusing on common effects (i.e., the “average ASD participant”), the case-control approach disguises considerable interindividual variation crucial for precision medicine.
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spelling pubmed-65513482019-06-10 Dissecting the Heterogeneous Cortical Anatomy of Autism Spectrum Disorder Using Normative Models Zabihi, Mariam Oldehinkel, Marianne Wolfers, Thomas Frouin, Vincent Goyard, David Loth, Eva Charman, Tony Tillmann, Julian Banaschewski, Tobias Dumas, Guillaume Holt, Rosemary Baron-Cohen, Simon Durston, Sarah Bölte, Sven Murphy, Declan Ecker, Christine Buitelaar, Jan K. Beckmann, Christian F. Marquand, Andre F. Biol Psychiatry Cogn Neurosci Neuroimaging Article BACKGROUND: The neuroanatomical basis of autism spectrum disorder (ASD) has remained elusive, mostly owing to high biological and clinical heterogeneity among diagnosed individuals. Despite considerable effort toward understanding ASD using neuroimaging biomarkers, heterogeneity remains a barrier, partly because studies mostly employ case-control approaches, which assume that the clinical group is homogeneous. METHODS: Here, we used an innovative normative modeling approach to parse biological heterogeneity in ASD. We aimed to dissect the neuroanatomy of ASD by mapping the deviations from a typical pattern of neuroanatomical development at the level of the individual and to show the necessity to look beyond the case-control paradigm to understand the neurobiology of ASD. We first estimated a vertexwise normative model of cortical thickness development using Gaussian process regression, then mapped the deviation of each participant from the typical pattern. For this, we employed a heterogeneous cross-sectional sample of 206 typically developing individuals (127 males) and 321 individuals with ASD (232 males) (6–31 years of age). RESULTS: We found few case-control differences, but the ASD cohort showed highly individualized patterns of deviations in cortical thickness that were widespread across the brain. These deviations correlated with severity of repetitive behaviors and social communicative symptoms, although only repetitive behaviors survived corrections for multiple testing. CONCLUSIONS: Our results 1) reinforce the notion that individuals with ASD show distinct, highly individualized trajectories of brain development and 2) show that by focusing on common effects (i.e., the “average ASD participant”), the case-control approach disguises considerable interindividual variation crucial for precision medicine. Elsevier, Inc 2019-06 /pmc/articles/PMC6551348/ /pubmed/30799285 http://dx.doi.org/10.1016/j.bpsc.2018.11.013 Text en © 2019 Society of Biological Psychiatry. Elsevier Inc. All rights reserved. http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Zabihi, Mariam
Oldehinkel, Marianne
Wolfers, Thomas
Frouin, Vincent
Goyard, David
Loth, Eva
Charman, Tony
Tillmann, Julian
Banaschewski, Tobias
Dumas, Guillaume
Holt, Rosemary
Baron-Cohen, Simon
Durston, Sarah
Bölte, Sven
Murphy, Declan
Ecker, Christine
Buitelaar, Jan K.
Beckmann, Christian F.
Marquand, Andre F.
Dissecting the Heterogeneous Cortical Anatomy of Autism Spectrum Disorder Using Normative Models
title Dissecting the Heterogeneous Cortical Anatomy of Autism Spectrum Disorder Using Normative Models
title_full Dissecting the Heterogeneous Cortical Anatomy of Autism Spectrum Disorder Using Normative Models
title_fullStr Dissecting the Heterogeneous Cortical Anatomy of Autism Spectrum Disorder Using Normative Models
title_full_unstemmed Dissecting the Heterogeneous Cortical Anatomy of Autism Spectrum Disorder Using Normative Models
title_short Dissecting the Heterogeneous Cortical Anatomy of Autism Spectrum Disorder Using Normative Models
title_sort dissecting the heterogeneous cortical anatomy of autism spectrum disorder using normative models
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6551348/
https://www.ncbi.nlm.nih.gov/pubmed/30799285
http://dx.doi.org/10.1016/j.bpsc.2018.11.013
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