Cross-sectional and longitudinal neuroanatomical profiles of distinct clinical (adaptive) outcomes in autism

Charlotte Pretzsch; Dorothea Floris; Tim Schäfer; Anke Bletsch; Caroline Gurr; Michael V. Lombardo; Christopher H. Chatham; Julian Tillmann; Tony Charman; Martina Arenella; Emily Jones; Sara Ambrosino; Thomas Bourgeron; Guillaume Dumas; Freddy Cliquet; Claire S. Leblond; Eva Loth; Beth Oakley; Jan Buitelaar; Simon Baron-Cohen; Christian F. Beckmann; Antonio M. Persico; Tobias Banaschewski; Sarah Durston; Christine Freitag; Declan Murphy; Christine Ecker

doi:10.1038/s41380-023-02016-z

Cross-sectional and longitudinal neuroanatomical profiles of distinct clinical (adaptive) outcomes in autism

Charlotte Pretzsch
, Dorothea Floris
, Tim Schäfer
, Anke Bletsch
, Caroline Gurr
, Michael V. Lombardo
, Christopher H. Chatham
, Julian Tillmann
, Tony Charman
, Martina Arenella
, Emily Jones
, Sara Ambrosino
, Thomas Bourgeron
, Guillaume Dumas
, Freddy Cliquet
, Claire S. Leblond
, Eva Loth
, Beth Oakley
, Jan Buitelaar
, Simon Baron-Cohen

Christian F. Beckmann, Antonio M. Persico, Tobias Banaschewski, Sarah Durston, Christine Freitag, Declan Murphy, Christine Ecker

Utrecht University
Donders Institute for Brain, Cognition and Behaviour
Goethe University Frankfurt Hospital
Goethe University Frankfurt
University of Cambridge
King's College London
Institute of Social Psychiatry
Autism Research Centre
University of Cyprus
Istituto Italiano di Tecnologia
Roche Innovation Centre Basel
Birkbeck, University of London
Unité de Biologie du Développement, Institut Pasteur, Paris, France.
University of Paris VII - Denis Diderot University
Université Paris Diderot
Université de Paris
University Paris Descartes
CNRS Centre National de la Recerche Scientifique
University of Paris XI - University of Paris-Sud
University of Montreal
McGill University
Cambridgeshire and Peterborough NHS Foundation Trust
Department of Neurology
Karakter Child and Adolescent Psychiatry University Centre
University of Oxford
Radboud University Nijmegen
Radboud University Medical Center
Policlinico Universitario
Mafalda Luce Center for Pervasive Developmental Disorders
University Campus Bio-Medico
SEAM, University of Messina
Azienda Ospedaliero - Universitaria di Modena Policlinico
Universitatsklinikum Mannheim
Tel Aviv University
Universidade de Sao Paulo - USP

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

12 Citations (Scopus)

191 Downloads (Pure)

Abstract

Individuals with autism spectrum disorder (henceforth referred to as autism) display significant variation in clinical outcome. For instance, across age, some individuals’ adaptive skills naturally improve or remain stable, while others’ decrease. To pave the way for ‘precision-medicine’ approaches, it is crucial to identify the cross-sectional and, given the developmental nature of autism, longitudinal neurobiological (including neuroanatomical and linked genetic) correlates of this variation. We conducted a longitudinal follow-up study of 333 individuals (161 autistic and 172 neurotypical individuals, aged 6–30 years), with two assessment time points separated by ~12–24 months. We collected behavioural (Vineland Adaptive Behaviour Scale-II, VABS-II) and neuroanatomical (structural magnetic resonance imaging) data. Autistic participants were grouped into clinically meaningful “Increasers”, “No-changers”, and “Decreasers” in adaptive behaviour (based on VABS-II scores). We compared each clinical subgroup’s neuroanatomy (surface area and cortical thickness at T1, ∆T (intra-individual change) and T2) to that of the neurotypicals. Next, we explored the neuroanatomical differences’ potential genomic associates using the Allen Human Brain Atlas. Clinical subgroups had distinct neuroanatomical profiles in surface area and cortical thickness at baseline, neuroanatomical development, and follow-up. These profiles were enriched for genes previously associated with autism and for genes previously linked to neurobiological pathways implicated in autism (e.g. excitation-inhibition systems). Our findings suggest that distinct clinical outcomes (i.e. intra-individual change in clinical profiles) linked to autism core symptoms are associated with atypical cross-sectional and longitudinal, i.e. developmental, neurobiological profiles. If validated, our findings may advance the development of interventions, e.g. targeting mechanisms linked to relatively poorer outcomes.

Original language	English
Pages (from-to)	2158-2169
Number of pages	12
Journal	Molecular Psychiatry
Volume	28
Issue number	5
Early online date	29 Mar 2023
DOIs	https://doi.org/10.1038/s41380-023-02016-z
Publication status	Published - May 2023

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Pretzsch, C., Floris, D., Schäfer, T., Bletsch, A., Gurr, C., Lombardo, M. V., Chatham, C. H., Tillmann, J., Charman, T., Arenella, M., Jones, E., Ambrosino, S., Bourgeron, T., Dumas, G., Cliquet, F., Leblond, C. S., Loth, E., Oakley, B., Buitelaar, J., ... Ecker, C. (2023). Cross-sectional and longitudinal neuroanatomical profiles of distinct clinical (adaptive) outcomes in autism. Molecular Psychiatry, 28(5), 2158-2169. https://doi.org/10.1038/s41380-023-02016-z

@article{2fd891b238574820a33af8f232ea57b3,

title = "Cross-sectional and longitudinal neuroanatomical profiles of distinct clinical (adaptive) outcomes in autism",

abstract = "Individuals with autism spectrum disorder (henceforth referred to as autism) display significant variation in clinical outcome. For instance, across age, some individuals{\textquoteright} adaptive skills naturally improve or remain stable, while others{\textquoteright} decrease. To pave the way for {\textquoteleft}precision-medicine{\textquoteright} approaches, it is crucial to identify the cross-sectional and, given the developmental nature of autism, longitudinal neurobiological (including neuroanatomical and linked genetic) correlates of this variation. We conducted a longitudinal follow-up study of 333 individuals (161 autistic and 172 neurotypical individuals, aged 6–30 years), with two assessment time points separated by \textasciitilde{}12–24 months. We collected behavioural (Vineland Adaptive Behaviour Scale-II, VABS-II) and neuroanatomical (structural magnetic resonance imaging) data. Autistic participants were grouped into clinically meaningful “Increasers”, “No-changers”, and “Decreasers” in adaptive behaviour (based on VABS-II scores). We compared each clinical subgroup{\textquoteright}s neuroanatomy (surface area and cortical thickness at T1, ∆T (intra-individual change) and T2) to that of the neurotypicals. Next, we explored the neuroanatomical differences{\textquoteright} potential genomic associates using the Allen Human Brain Atlas. Clinical subgroups had distinct neuroanatomical profiles in surface area and cortical thickness at baseline, neuroanatomical development, and follow-up. These profiles were enriched for genes previously associated with autism and for genes previously linked to neurobiological pathways implicated in autism (e.g. excitation-inhibition systems). Our findings suggest that distinct clinical outcomes (i.e. intra-individual change in clinical profiles) linked to autism core symptoms are associated with atypical cross-sectional and longitudinal, i.e. developmental, neurobiological profiles. If validated, our findings may advance the development of interventions, e.g. targeting mechanisms linked to relatively poorer outcomes.",

author = "Charlotte Pretzsch and Dorothea Floris and Tim Sch{\"a}fer and Anke Bletsch and Caroline Gurr and Lombardo, \{Michael V.\} and Chatham, \{Christopher H.\} and Julian Tillmann and Tony Charman and Martina Arenella and Emily Jones and Sara Ambrosino and Thomas Bourgeron and Guillaume Dumas and Freddy Cliquet and Leblond, \{Claire S.\} and Eva Loth and Beth Oakley and Jan Buitelaar and Simon Baron-Cohen and Beckmann, \{Christian F.\} and Persico, \{Antonio M.\} and Tobias Banaschewski and Sarah Durston and Christine Freitag and Declan Murphy and Christine Ecker",

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{\textquoteright}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 (IHI-JU2). This work was further supported by the European Union Horizon-2020 programme CANDY (Grant Agreement No. 847818). CMF acknowledges support from the European Union and the German Research Association (DFG). DGM acknowledges support from the NIHR Maudsley Biomedical Research Centre. We thank all participants of the LEAP study. Many thanks also to ABI for his support and the best coffee in London. 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{\textquoteright}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 (IHI-JU2). This work was further supported by the European Union Horizon-2020 programme CANDY (Grant Agreement No. 847818). CMF acknowledges support from the European Union and the German Research Association (DFG). DGM acknowledges support from the NIHR Maudsley Biomedical Research Centre. We thank all participants of the LEAP study. Many thanks also to ABI for his support and the best coffee in London. Publisher Copyright: {\textcopyright} 2023, The Author(s).",

year = "2023",

month = may,

doi = "10.1038/s41380-023-02016-z",

language = "English",

volume = "28",

pages = "2158--2169",

journal = "Molecular Psychiatry",

issn = "1359-4184",

publisher = "Springer Nature [academic journals on nature.com]",

number = "5",

}

Pretzsch, C, Floris, D, Schäfer, T, Bletsch, A, Gurr, C, Lombardo, MV, Chatham, CH, Tillmann, J , Charman, T , Arenella, M, Jones, E, Ambrosino, S, Bourgeron, T, Dumas, G, Cliquet, F, Leblond, CS, Loth, E , Oakley, B, Buitelaar, J, Baron-Cohen, S, Beckmann, CF, Persico, AM, Banaschewski, T, Durston, S, Freitag, C , Murphy, D & Ecker, C 2023, 'Cross-sectional and longitudinal neuroanatomical profiles of distinct clinical (adaptive) outcomes in autism', Molecular Psychiatry, vol. 28, no. 5, pp. 2158-2169. https://doi.org/10.1038/s41380-023-02016-z

TY - JOUR

T1 - Cross-sectional and longitudinal neuroanatomical profiles of distinct clinical (adaptive) outcomes in autism

AU - Pretzsch, Charlotte

AU - Floris, Dorothea

AU - Schäfer, Tim

AU - Bletsch, Anke

AU - Gurr, Caroline

AU - Lombardo, Michael V.

AU - Chatham, Christopher H.

AU - Tillmann, Julian

AU - Charman, Tony

AU - Arenella, Martina

AU - Jones, Emily

AU - Ambrosino, Sara

AU - Bourgeron, Thomas

AU - Dumas, Guillaume

AU - Cliquet, Freddy

AU - Leblond, Claire S.

AU - Loth, Eva

AU - Oakley, Beth

AU - Buitelaar, Jan

AU - Baron-Cohen, Simon

AU - Beckmann, Christian F.

AU - Persico, Antonio M.

AU - Banaschewski, Tobias

AU - Durston, Sarah

AU - Freitag, Christine

AU - Murphy, Declan

AU - Ecker, Christine

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 (IHI-JU2). This work was further supported by the European Union Horizon-2020 programme CANDY (Grant Agreement No. 847818). CMF acknowledges support from the European Union and the German Research Association (DFG). DGM acknowledges support from the NIHR Maudsley Biomedical Research Centre. We thank all participants of the LEAP study. Many thanks also to ABI for his support and the best coffee in London. 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 (IHI-JU2). This work was further supported by the European Union Horizon-2020 programme CANDY (Grant Agreement No. 847818). CMF acknowledges support from the European Union and the German Research Association (DFG). DGM acknowledges support from the NIHR Maudsley Biomedical Research Centre. We thank all participants of the LEAP study. Many thanks also to ABI for his support and the best coffee in London. Publisher Copyright: © 2023, The Author(s).

PY - 2023/5

Y1 - 2023/5

N2 - Individuals with autism spectrum disorder (henceforth referred to as autism) display significant variation in clinical outcome. For instance, across age, some individuals’ adaptive skills naturally improve or remain stable, while others’ decrease. To pave the way for ‘precision-medicine’ approaches, it is crucial to identify the cross-sectional and, given the developmental nature of autism, longitudinal neurobiological (including neuroanatomical and linked genetic) correlates of this variation. We conducted a longitudinal follow-up study of 333 individuals (161 autistic and 172 neurotypical individuals, aged 6–30 years), with two assessment time points separated by ~12–24 months. We collected behavioural (Vineland Adaptive Behaviour Scale-II, VABS-II) and neuroanatomical (structural magnetic resonance imaging) data. Autistic participants were grouped into clinically meaningful “Increasers”, “No-changers”, and “Decreasers” in adaptive behaviour (based on VABS-II scores). We compared each clinical subgroup’s neuroanatomy (surface area and cortical thickness at T1, ∆T (intra-individual change) and T2) to that of the neurotypicals. Next, we explored the neuroanatomical differences’ potential genomic associates using the Allen Human Brain Atlas. Clinical subgroups had distinct neuroanatomical profiles in surface area and cortical thickness at baseline, neuroanatomical development, and follow-up. These profiles were enriched for genes previously associated with autism and for genes previously linked to neurobiological pathways implicated in autism (e.g. excitation-inhibition systems). Our findings suggest that distinct clinical outcomes (i.e. intra-individual change in clinical profiles) linked to autism core symptoms are associated with atypical cross-sectional and longitudinal, i.e. developmental, neurobiological profiles. If validated, our findings may advance the development of interventions, e.g. targeting mechanisms linked to relatively poorer outcomes.

AB - Individuals with autism spectrum disorder (henceforth referred to as autism) display significant variation in clinical outcome. For instance, across age, some individuals’ adaptive skills naturally improve or remain stable, while others’ decrease. To pave the way for ‘precision-medicine’ approaches, it is crucial to identify the cross-sectional and, given the developmental nature of autism, longitudinal neurobiological (including neuroanatomical and linked genetic) correlates of this variation. We conducted a longitudinal follow-up study of 333 individuals (161 autistic and 172 neurotypical individuals, aged 6–30 years), with two assessment time points separated by ~12–24 months. We collected behavioural (Vineland Adaptive Behaviour Scale-II, VABS-II) and neuroanatomical (structural magnetic resonance imaging) data. Autistic participants were grouped into clinically meaningful “Increasers”, “No-changers”, and “Decreasers” in adaptive behaviour (based on VABS-II scores). We compared each clinical subgroup’s neuroanatomy (surface area and cortical thickness at T1, ∆T (intra-individual change) and T2) to that of the neurotypicals. Next, we explored the neuroanatomical differences’ potential genomic associates using the Allen Human Brain Atlas. Clinical subgroups had distinct neuroanatomical profiles in surface area and cortical thickness at baseline, neuroanatomical development, and follow-up. These profiles were enriched for genes previously associated with autism and for genes previously linked to neurobiological pathways implicated in autism (e.g. excitation-inhibition systems). Our findings suggest that distinct clinical outcomes (i.e. intra-individual change in clinical profiles) linked to autism core symptoms are associated with atypical cross-sectional and longitudinal, i.e. developmental, neurobiological profiles. If validated, our findings may advance the development of interventions, e.g. targeting mechanisms linked to relatively poorer outcomes.

UR - https://www.scopus.com/pages/publications/85151399815

U2 - 10.1038/s41380-023-02016-z

DO - 10.1038/s41380-023-02016-z

M3 - Article

C2 - 36991132

AN - SCOPUS:85151399815

SN - 1359-4184

VL - 28

SP - 2158

EP - 2169

JO - Molecular Psychiatry

JF - Molecular Psychiatry

IS - 5

ER -

Cross-sectional and longitudinal neuroanatomical profiles of distinct clinical (adaptive) outcomes in autism

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