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Christine Ecker, Charlotte M. Pretzsch, Anke Bletsch, Caroline Mann, Tim Schaefer, Sara Ambrosino, Julian Tillmann, Afsheen Yousaf, et al.
(2022).
Interindividual Differences in Cortical Thickness and Their Genomic Underpinnings in Autism Spectrum Disorder.
American Journal of Psychiatry, 179(3), 242-254.
American Psychiatric Association Publishing.
- Date de publication
-
01/03/2022
- Identifiant
-
10.1176/appi.ajp.2021.20050630
- Auteurs
-
Christine Ecker,
Charlotte M. Pretzsch,
Anke Bletsch,
Caroline Mann,
Tim Schaefer,
Sara Ambrosino,
Julian Tillmann,
Afsheen Yousaf,
Andreas Chiocchetti,
Michael V. Lombardo,
Varun Warrier,
Nico Bast,
Carolin Moessnang,
Sarah Baumeister,
Flavio Dell’Acqua,
Dorothea L. Floris,
Mariam Zabihi,
Andre Marquand,
Freddy Cliquet,
Claire Leblond,
Clara Moreau,
Nick Puts,
Tobias Banaschewski,
Emily J.H. Jones,
Luke Mason,
Sven Bölte,
Andreas Meyer-Lindenberg,
Antonio M. Persico,
Sarah Durston,
Simon Baron-Cohen,
Will Spooren,
Eva Loth,
Christine M. Freitag,
Tony Charman,
Guillaume Dumas,
Thomas Bourgeron,
Christian F. Beckmann,
Jan K. Buitelaar,
Declan G.M. Murphy
- Source
- American Journal of Psychiatry
- Détails
- 179(3), 242-254
- Type de référence
- article
- Éditeur
- American Psychiatric Association Publishing
- Source de métadonnées
- crossref
Résumé
OBJECTIVE: Autism spectrum disorder (ASD) is accompanied by highly individualized neuroanatomical deviations that potentially map onto distinct genotypes and clinical phenotypes. This study aimed to link differences in brain anatomy to specific biological pathways to pave the way toward targeted therapeutic interventions. METHODS: The authors examined neurodevelopmental differences in cortical thickness and their genomic underpinnings in a large and clinically diverse sample of 360 individuals with ASD and 279 typically developing control subjects (ages 6-30 years) within the EU-AIMS Longitudinal European Autism Project (LEAP). The authors also examined neurodevelopmental differences and their potential pathophysiological mechanisms between clinical ASD subgroups that differed in the severity and pattern of sensory features. RESULTS: In addition to significant between-group differences in "core" ASD brain regions (i.e., fronto-temporal and cingulate regions), individuals with ASD manifested as neuroanatomical outliers within the neurotypical cortical thickness range in a wider neural system, which was enriched for genes known to be implicated in ASD on the genetic and/or transcriptomic level. Within these regions, the individuals' total (i.e., accumulated) degree of neuroanatomical atypicality was significantly correlated with higher polygenic scores for ASD and other psychiatric conditions, and it scaled with measures of symptom severity. Differences in cortical thickness deviations were also associated with distinct sensory subgroups, especially in brain regions expressing genes involved in excitatory rather than inhibitory neurotransmission. CONCLUSIONS: The study findings corroborate the link between macroscopic differences in brain anatomy and the molecular mechanisms underpinning heterogeneity in ASD, and provide future targets for stratification and subtyping.
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