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 - http://www.scopus.com/inward/record.url?scp=85151399815&partnerID=8YFLogxK
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 -
