Fractionating autism based on neuroanatomical normative modeling

Mariam Zabihi (1, 2) , Dorothea L. Floris (1, 2) , Seyed Mostafa Kia (1, 2) , Thomas Wolfers (1, 3, 4) , Julian Tillmann (5, 6) , Alberto Llera Arenas (1, 2) , Carolin Moessnang (7) , Tobias Banaschewski (8, 7) , Rosemary Holt (9) , Simon Baron-Cohen (9) , Eva Loth (5) , Tony Charman (5) , Thomas Bourgeron (10) , Declan Murphy (5) , Christine Ecker (5, 11) , Jan K. Buitelaar (1, 2, 12) , Christian F. Beckmann (1, 2, 13) , Andre Marquand (1, 2, 5) , Eu-Aims Leap Group

1 Donders Institute for Brain, Cognition and Behaviour
2 Radboud University Medical Center [Nijmegen]
3 UiO - University of Oslo
4 Oslo University Hospital [Oslo]
5 King‘s College London
6 University of Vienna [Vienna]
7 Universität Heidelberg [Heidelberg] = Heidelberg University
8 University Hospital Mannheim | Universitätsmedizin Mannheim
9 CAM - University of Cambridge [UK]
10 GHFC (UMR_3571 / U-Pasteur_1) - Génétique humaine et fonctions cognitives - Human Genetics and Cognitive Functions
11 Goethe-Universität Frankfurt am Main
12 Karakter Child and Adolescent Psychiatry University Centre [Nijmegen]
13 University of Oxford

Autism is a complex neurodevelopmental condition with substantial phenotypic, biological, and etiologic heterogeneity. It remains a challenge to identify biomarkers to stratify autism into replicable cognitive or biological subtypes. Here, we aim to introduce a novel methodological framework for parsing neuroanatomical subtypes within a large cohort of individuals with autism. We used cortical thickness (CT) in a large and well-characterized sample of 316 participants with autism (88 female, age mean: 17.2 ± 5.7) and 206 with neurotypical development (79 female, age mean: 17.5 ± 6.1) aged 6–31 years across six sites from the EU-AIMS multi-center Longitudinal European Autism Project. Five biologically based putative subtypes were derived using normative modeling of CT and spectral clustering. Three of these clusters showed relatively widespread decreased CT and two showed relatively increased CT. These subtypes showed morphometric differences from one another, providing a potential explanation for inconsistent case–control findings in autism, and loaded differentially and more strongly onto symptoms and polygenic risk, indicating a dilution of clinical effects across heterogeneous cohorts. Our results provide an important step towards parsing the heterogeneous neurobiology of autism.

Domaines: Neurosciences

Mariam Zabihi, Dorothea L. Floris, Seyed Mostafa Kia, Thomas Wolfers, Julian Tillmann, et al.. Fractionating autism based on neuroanatomical normative modeling. Translational Psychiatry, 2020, 10 (1), pp.384. ⟨10.1038/s41398-020-01057-0⟩. ⟨pasteur-03325386⟩