Fractionating autism based on neuroanatomical normative modeling.
Journal
Translational psychiatry
ISSN: 2158-3188
Titre abrégé: Transl Psychiatry
Pays: United States
ID NLM: 101562664
Informations de publication
Date de publication:
06 11 2020
06 11 2020
Historique:
received:
08
06
2020
accepted:
19
10
2020
revised:
29
09
2020
pubmed:
8
11
2020
medline:
19
5
2021
entrez:
7
11
2020
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 33159037
doi: 10.1038/s41398-020-01057-0
pii: 10.1038/s41398-020-01057-0
pmc: PMC7648836
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
384Subventions
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/N026063/1
Pays : United Kingdom
Organisme : Nederlandse Organisatie voor Wetenschappelijk Onderzoek (Netherlands Organisation for Scientific Research)
ID : 864.12.003
Pays : International
Organisme : Nederlandse Organisatie voor Wetenschappelijk Onderzoek (Netherlands Organisation for Scientific Research)
ID : 016.156.415
Pays : International
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