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Interindividual Differences in Cortical Thickness and Their Genomic Underpinnings in Autism Spectrum Disorder. | LitMetric

Interindividual Differences in Cortical Thickness and Their Genomic Underpinnings in Autism Spectrum Disorder.

Am J Psychiatry

Department of Child and Adolescent Psychiatry, University Hospital, Goethe University, Frankfurt am Main, Germany (Ecker, Bletsch, Mann, Schaefer, Yousaf, Chiocchetti, Bast, Freitag); Department of Forensic and Neurodevelopmental Sciences (Ecker, Pretzsch, Dell'Acqua, Puts, Loth, Murphy) and Department of Psychology (Tillmann, Charman), Institute of Psychiatry, Psychology, and Neuroscience, King's College London; Department of Psychiatry, University Medical Center Utrecht Brain Center, Utrecht University, Utrecht, the Netherlands (Ambrosino, Durston); Laboratory for Autism and Neurodevelopmental Disorders, Center for Neuroscience and Cognitive Systems, University of Trento, Istituto Italiano di Tecnologia, Rovereto, Italy (Lombardo); Autism Research Centre, Department of Psychiatry, University of Cambridge, Cambridge, U.K. (Lombardo, Warrier, Baron-Cohen); Department of Psychiatry and Psychotherapy (Moessnang, Baumeister, Meyer-Lindenberg) and Department of Child and Adolescent Psychiatry (Moessnang, Baumeister, Banaschewski), Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany; Department of Cognitive Neuroscience, Donders Institute for Brain, Cognition, and Behavior, Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands (Floris, Zabihi, Marquand, Beckmann, Buitelaar); Human Genetics and Cognitive Functions Unit, Institut Pasteur, University of Paris, Paris (Cliquet, Leblond, Moreau, Dumas, Bourgeron); Centre for Brain and Cognitive Development, Birkbeck, University of London, London (Jones, Mason); Center for Neurodevelopmental Disorders (KIND), Center for Psychiatry Research, Department of Women's and Children's Health, Karolinska Institutet and Stockholm Health Care Services, and Department of Child and Adolescent Psychiatry, Stockholm Health Care Services, Region Stockholm, Sweden (Bölte); Department of Child and Adolescent Neuropsychiatry, Gaetano Martino University Hospital, University of Messina, Messina, Italy (Persico); Roche Pharmaceutical Research and Early Development, NORD Discovery and Translational Area, Roche Innovation Center Basel, Switzerland (Spooren).

Published: March 2022

AI Article Synopsis

  • - The study investigates the link between brain anatomy and genetics in individuals with autism spectrum disorder (ASD), focusing on differences in cortical thickness across a diverse group of participants.
  • - Results show significant differences in key brain regions between those with ASD and typically developing individuals, revealing neuroanatomical deviations that correlate with genetic predisposition and symptom severity.
  • - Findings support the connection between brain structure and the molecular mechanisms involved in ASD, suggesting pathways for tailored therapeutic interventions and better understanding of the disorder's complexity.

Article Abstract

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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Source
http://dx.doi.org/10.1176/appi.ajp.2021.20050630DOI Listing

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