In-depth characterization of neuroradiological findings in a large sample of individuals with autism spectrum disorder and controls

The EU-AIMS LEAP Group

doi:10.1016/j.nicl.2022.103118

In-depth characterization of neuroradiological findings in a large sample of individuals with autism spectrum disorder and controls

The EU-AIMS LEAP Group

Research output: Contribution to journal › Article › peer-review

5 Citations (Scopus)

Abstract

Background: Autism spectrum disorder (ASD) is a group of neurodevelopmental conditions associated with quantitative differences in cortical and subcortical brain morphometry. Qualitative assessment of brain morphology provides complementary information on the possible underlying neurobiology. Studies of neuroradiological findings in ASD have rendered mixed results, and await robust replication in a sizable and independent sample. Methods: We systematically and comprehensively assessed neuroradiological findings in a large cohort of participants with ASD and age-matched controls (total N = 620, 348 ASD and 272 controls), including 70 participants with intellectual disability (47 ASD, 23 controls). We developed a comprehensive scoring system, augmented by standardized biometric measures. Results: There was a higher incidence of neuroradiological findings in individuals with ASD (89.4 %) compared to controls (83.8 %, p = .042). Certain findings were also more common in ASD, in particular opercular abnormalities (OR 1.9, 95 % CI 1.3–3.6) and mega cisterna magna (OR 2.4, 95 % CI 1.4–4.0) reached significance when using FDR, whereas increases in macrocephaly (OR 2.0, 95 % CI 1.2–3.2), cranial deformities (OR 2.4, 95 % CI: 1.0–5.8), calvarian / dural thickening (OR 1.5, 95 % CI 1.0–2.3), ventriculomegaly (OR 3.4, 95 % CI 1.3–9.2), and hypoplasia of the corpus callosum (OR 2.7, 95 % CI 1.1–6.3) did not survive this correction. Furthermore, neuroradiological findings were more likely to occur in isolation in controls, whereas they clustered more frequently in ASD. The incidence of neuroradiological findings was higher in individuals with mild intellectual disability (95.7 %), irrespective of ASD diagnosis. Conclusion: There was a subtly higher prevalence of neuroradiological findings in ASD, which did not appear to be specific to the condition. Individual findings or clusters of findings may point towards the neurodevelopmental mechanisms involved in individual cases. As such, clinical MRI assessments may be useful to guide further etiopathological (genetic) investigations, and are potentially valuable to fundamental ASD research.

Original language	English
Article number	103118
Journal	NeuroImage: Clinical
Volume	35
Early online date	19 Jul 2022
DOIs	https://doi.org/10.1016/j.nicl.2022.103118
Publication status	E-pub ahead of print - 19 Jul 2022

Keywords

ASD
Brain structural MRI
Radiological assessment

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10.1016/j.nicl.2022.103118Licence: CC BY

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@article{6136b6feefe1426b90fba932588672b4,

title = "In-depth characterization of neuroradiological findings in a large sample of individuals with autism spectrum disorder and controls",

abstract = "Background: Autism spectrum disorder (ASD) is a group of neurodevelopmental conditions associated with quantitative differences in cortical and subcortical brain morphometry. Qualitative assessment of brain morphology provides complementary information on the possible underlying neurobiology. Studies of neuroradiological findings in ASD have rendered mixed results, and await robust replication in a sizable and independent sample. Methods: We systematically and comprehensively assessed neuroradiological findings in a large cohort of participants with ASD and age-matched controls (total N = 620, 348 ASD and 272 controls), including 70 participants with intellectual disability (47 ASD, 23 controls). We developed a comprehensive scoring system, augmented by standardized biometric measures. Results: There was a higher incidence of neuroradiological findings in individuals with ASD (89.4 %) compared to controls (83.8 %, p = .042). Certain findings were also more common in ASD, in particular opercular abnormalities (OR 1.9, 95 % CI 1.3–3.6) and mega cisterna magna (OR 2.4, 95 % CI 1.4–4.0) reached significance when using FDR, whereas increases in macrocephaly (OR 2.0, 95 % CI 1.2–3.2), cranial deformities (OR 2.4, 95 % CI: 1.0–5.8), calvarian / dural thickening (OR 1.5, 95 % CI 1.0–2.3), ventriculomegaly (OR 3.4, 95 % CI 1.3–9.2), and hypoplasia of the corpus callosum (OR 2.7, 95 % CI 1.1–6.3) did not survive this correction. Furthermore, neuroradiological findings were more likely to occur in isolation in controls, whereas they clustered more frequently in ASD. The incidence of neuroradiological findings was higher in individuals with mild intellectual disability (95.7 %), irrespective of ASD diagnosis. Conclusion: There was a subtly higher prevalence of neuroradiological findings in ASD, which did not appear to be specific to the condition. Individual findings or clusters of findings may point towards the neurodevelopmental mechanisms involved in individual cases. As such, clinical MRI assessments may be useful to guide further etiopathological (genetic) investigations, and are potentially valuable to fundamental ASD research.",

keywords = "ASD, Brain structural MRI, Radiological assessment",

author = "{The EU-AIMS LEAP Group} and Sara Ambrosino and Hasnaa Elbendary and Maarten Lequin and Dominique Rijkelijkhuizen and Tobias Banaschewski and Simon Baron-Cohen and Nico Bast and Sarah Baumeister and Jan Buitelaar and Tony Charman and Daisy Crawley and Flavio Dell'Acqua and Hannah Hayward and Rosemary Holt and Carolin Moessnang and Persico, {Antonio M.} and Roberto Sacco and {San Jos{\'e} C{\'a}ceres}, Antonia and Julian Tillmann and Eva Loth and Christine Ecker and Bob Oranje and Declan Murphy and Sarah Durston",

note = "Funding Information: The results leading to this publication have received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No 777394 for the project AIMS-2-TRIALS. This Joint Undertaking receives support from the European Union's Horizon 2020 research and innovation programme and EFPIA and AUTISM SPEAKS, Autistica, SFARI. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results. Any views expressed are those of the author(s) and not necessarily those of the funders. Funding Information: We would like to thank all participants and their families for participating in this study. We further wish to thank Miriam Douma, Tabitha Koops, Sara Post, Iris Selten, Alyssia Spaan, Maarten Steffers, and Anna Ver Loren van Themaat for their assistance with subject recruitment and acquisition of MRI scans throughout the running time of this study. We gratefully acknowledge the contributions of the EU-AIMS LEAP Group: Jumana Ahmad, Sara Ambrosino, Bonnie Auyeung, Tobias Banaschewski, Simon Baron-Cohen, Sarah Baumeister, Christian F. Beckmann, Sven B{\"o}lte, Thomas Bourgeron, Carsten Bours, Michael Brammer, Daniel Brandeis, Claudia Brogna, Yvette de Bruijn, Jan K. Buitelaar, Bhismadev Chakrabarti, Tony Charman, Mario Cirillo, Ineke Cornelissen, Daisy Crawley, Flavio Dell'Acqua, Francesco Di Salle, Guillaume Dumas, Sarah Durston, Christine Ecker, Fabrizio Esposito, Jessica Faulkner, Vincent Frouin, Pilar Garc{\'e}s, David Goyard, Lindsay Ham, Hannah Hayward, Joerg Hipp, Rosemary Holt, Mark H. Johnson, Emily J.H. Jones, Prantik Kundu, Meng-Chuan Lai, Xavier Liogier D'ardhuy, Michael V. Lombardo, Eva Loth, David J. Lythgoe, Ren{\'e} Mandl, Andre Marquand, Luke Mason, Maarten Mennes, Andreas Meyer-Lindenberg, Carolin Moessnang, Nico Mueller, Declan G.M. Murphy, Bethany Oakley, Laurence O'Dwyer, Marianne Oldehinkel, Bob Oranje, Gahan Pandina, Antonio M. Persico, Barbara Ruggeri, Annika Rausch, Amber Ruigrok, Jessica Sabet, Roberto Sacco, Antonia San Jos{\'e} C{\'a}ceres, Emily Simonoff, Will Spooren, Giacchino Tedeschi, Julian Tillmann, Roberto Toro, Heike Tost, Jack Waldman, Steve C.R. Williams, Caroline Wooldridge, and Marcel P. Zwiers. The primary contact for the EU-AIMS LEAP Group is Declan G. Murphy (Email: [email protected]). The results leading to this publication have received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No 777394 for the project AIMS-2-TRIALS. This Joint Undertaking receives support from the European Union's Horizon 2020 research and innovation programme and EFPIA and AUTISM SPEAKS, Autistica, SFARI. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results. Any views expressed are those of the author(s) and not necessarily those of the funders. Publisher Copyright: {\textcopyright} 2022 The Author(s)",

year = "2022",

month = jul,

day = "19",

doi = "10.1016/j.nicl.2022.103118",

language = "English",

volume = "35",

journal = "NeuroImage: Clinical",

issn = "2213-1582",

}

TY - JOUR

T1 - In-depth characterization of neuroradiological findings in a large sample of individuals with autism spectrum disorder and controls

AU - The EU-AIMS LEAP Group

AU - Ambrosino, Sara

AU - Elbendary, Hasnaa

AU - Lequin, Maarten

AU - Rijkelijkhuizen, Dominique

AU - Banaschewski, Tobias

AU - Baron-Cohen, Simon

AU - Bast, Nico

AU - Baumeister, Sarah

AU - Buitelaar, Jan

AU - Charman, Tony

AU - Crawley, Daisy

AU - Dell'Acqua, Flavio

AU - Hayward, Hannah

AU - Holt, Rosemary

AU - Moessnang, Carolin

AU - Persico, Antonio M.

AU - Sacco, Roberto

AU - San José Cáceres, Antonia

AU - Tillmann, Julian

AU - Loth, Eva

AU - Ecker, Christine

AU - Oranje, Bob

AU - Murphy, Declan

AU - Durston, Sarah

N1 - Funding Information: The results leading to this publication have received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No 777394 for the project AIMS-2-TRIALS. This Joint Undertaking receives support from the European Union's Horizon 2020 research and innovation programme and EFPIA and AUTISM SPEAKS, Autistica, SFARI. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results. Any views expressed are those of the author(s) and not necessarily those of the funders. Funding Information: We would like to thank all participants and their families for participating in this study. We further wish to thank Miriam Douma, Tabitha Koops, Sara Post, Iris Selten, Alyssia Spaan, Maarten Steffers, and Anna Ver Loren van Themaat for their assistance with subject recruitment and acquisition of MRI scans throughout the running time of this study. We gratefully acknowledge the contributions of the EU-AIMS LEAP Group: Jumana Ahmad, Sara Ambrosino, Bonnie Auyeung, Tobias Banaschewski, Simon Baron-Cohen, Sarah Baumeister, Christian F. Beckmann, Sven Bölte, Thomas Bourgeron, Carsten Bours, Michael Brammer, Daniel Brandeis, Claudia Brogna, Yvette de Bruijn, Jan K. Buitelaar, Bhismadev Chakrabarti, Tony Charman, Mario Cirillo, Ineke Cornelissen, Daisy Crawley, Flavio Dell'Acqua, Francesco Di Salle, Guillaume Dumas, Sarah Durston, Christine Ecker, Fabrizio Esposito, Jessica Faulkner, Vincent Frouin, Pilar Garcés, David Goyard, Lindsay Ham, Hannah Hayward, Joerg Hipp, Rosemary Holt, Mark H. Johnson, Emily J.H. Jones, Prantik Kundu, Meng-Chuan Lai, Xavier Liogier D'ardhuy, Michael V. Lombardo, Eva Loth, David J. Lythgoe, René Mandl, Andre Marquand, Luke Mason, Maarten Mennes, Andreas Meyer-Lindenberg, Carolin Moessnang, Nico Mueller, Declan G.M. Murphy, Bethany Oakley, Laurence O'Dwyer, Marianne Oldehinkel, Bob Oranje, Gahan Pandina, Antonio M. Persico, Barbara Ruggeri, Annika Rausch, Amber Ruigrok, Jessica Sabet, Roberto Sacco, Antonia San José Cáceres, Emily Simonoff, Will Spooren, Giacchino Tedeschi, Julian Tillmann, Roberto Toro, Heike Tost, Jack Waldman, Steve C.R. Williams, Caroline Wooldridge, and Marcel P. Zwiers. The primary contact for the EU-AIMS LEAP Group is Declan G. Murphy (Email: [email protected]). The results leading to this publication have received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No 777394 for the project AIMS-2-TRIALS. This Joint Undertaking receives support from the European Union's Horizon 2020 research and innovation programme and EFPIA and AUTISM SPEAKS, Autistica, SFARI. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results. Any views expressed are those of the author(s) and not necessarily those of the funders. Publisher Copyright: © 2022 The Author(s)

PY - 2022/7/19

Y1 - 2022/7/19

N2 - Background: Autism spectrum disorder (ASD) is a group of neurodevelopmental conditions associated with quantitative differences in cortical and subcortical brain morphometry. Qualitative assessment of brain morphology provides complementary information on the possible underlying neurobiology. Studies of neuroradiological findings in ASD have rendered mixed results, and await robust replication in a sizable and independent sample. Methods: We systematically and comprehensively assessed neuroradiological findings in a large cohort of participants with ASD and age-matched controls (total N = 620, 348 ASD and 272 controls), including 70 participants with intellectual disability (47 ASD, 23 controls). We developed a comprehensive scoring system, augmented by standardized biometric measures. Results: There was a higher incidence of neuroradiological findings in individuals with ASD (89.4 %) compared to controls (83.8 %, p = .042). Certain findings were also more common in ASD, in particular opercular abnormalities (OR 1.9, 95 % CI 1.3–3.6) and mega cisterna magna (OR 2.4, 95 % CI 1.4–4.0) reached significance when using FDR, whereas increases in macrocephaly (OR 2.0, 95 % CI 1.2–3.2), cranial deformities (OR 2.4, 95 % CI: 1.0–5.8), calvarian / dural thickening (OR 1.5, 95 % CI 1.0–2.3), ventriculomegaly (OR 3.4, 95 % CI 1.3–9.2), and hypoplasia of the corpus callosum (OR 2.7, 95 % CI 1.1–6.3) did not survive this correction. Furthermore, neuroradiological findings were more likely to occur in isolation in controls, whereas they clustered more frequently in ASD. The incidence of neuroradiological findings was higher in individuals with mild intellectual disability (95.7 %), irrespective of ASD diagnosis. Conclusion: There was a subtly higher prevalence of neuroradiological findings in ASD, which did not appear to be specific to the condition. Individual findings or clusters of findings may point towards the neurodevelopmental mechanisms involved in individual cases. As such, clinical MRI assessments may be useful to guide further etiopathological (genetic) investigations, and are potentially valuable to fundamental ASD research.

AB - Background: Autism spectrum disorder (ASD) is a group of neurodevelopmental conditions associated with quantitative differences in cortical and subcortical brain morphometry. Qualitative assessment of brain morphology provides complementary information on the possible underlying neurobiology. Studies of neuroradiological findings in ASD have rendered mixed results, and await robust replication in a sizable and independent sample. Methods: We systematically and comprehensively assessed neuroradiological findings in a large cohort of participants with ASD and age-matched controls (total N = 620, 348 ASD and 272 controls), including 70 participants with intellectual disability (47 ASD, 23 controls). We developed a comprehensive scoring system, augmented by standardized biometric measures. Results: There was a higher incidence of neuroradiological findings in individuals with ASD (89.4 %) compared to controls (83.8 %, p = .042). Certain findings were also more common in ASD, in particular opercular abnormalities (OR 1.9, 95 % CI 1.3–3.6) and mega cisterna magna (OR 2.4, 95 % CI 1.4–4.0) reached significance when using FDR, whereas increases in macrocephaly (OR 2.0, 95 % CI 1.2–3.2), cranial deformities (OR 2.4, 95 % CI: 1.0–5.8), calvarian / dural thickening (OR 1.5, 95 % CI 1.0–2.3), ventriculomegaly (OR 3.4, 95 % CI 1.3–9.2), and hypoplasia of the corpus callosum (OR 2.7, 95 % CI 1.1–6.3) did not survive this correction. Furthermore, neuroradiological findings were more likely to occur in isolation in controls, whereas they clustered more frequently in ASD. The incidence of neuroradiological findings was higher in individuals with mild intellectual disability (95.7 %), irrespective of ASD diagnosis. Conclusion: There was a subtly higher prevalence of neuroradiological findings in ASD, which did not appear to be specific to the condition. Individual findings or clusters of findings may point towards the neurodevelopmental mechanisms involved in individual cases. As such, clinical MRI assessments may be useful to guide further etiopathological (genetic) investigations, and are potentially valuable to fundamental ASD research.

KW - ASD

KW - Brain structural MRI

KW - Radiological assessment

UR - http://www.scopus.com/inward/record.url?scp=85134691838&partnerID=8YFLogxK

U2 - 10.1016/j.nicl.2022.103118

DO - 10.1016/j.nicl.2022.103118

M3 - Article

AN - SCOPUS:85134691838

SN - 2213-1582

VL - 35

JO - NeuroImage: Clinical

JF - NeuroImage: Clinical

M1 - 103118

ER -

In-depth characterization of neuroradiological findings in a large sample of individuals with autism spectrum disorder and controls

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Keywords

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