Inter-individual differences in cortical thickness and their genomic underpinnings in autism spectrum disorder

Ecker, C. and Preztsch, C. and Jones, Emily J.H. and Leap Team, The and Murphy, D. (2022) Inter-individual differences in cortical thickness and their genomic underpinnings in autism spectrum disorder. American Journal of Psychiatry 179 (3), pp. 242-254. ISSN 0002-953X.

Abstract

Objective. Autism Spectrum Disorder (ASD) is accompanied by highly individualized neuroanatomical deviations that potentially map onto distinct genotypes and clinical phenotypes. However, the link between biological pathways and differences in brain anatomy, which may pave the way towards targeted therapeutic interventions, remains poorly understood. Methods. Our study examined neurodevelopmental differences in cortical thickness (CT) and their genomic underpinnings in a large and clinically diverse sample of 360 individuals with ASD and 270 typically developing controls (aged 6-30 years) within the EU-AIMS Longitudinal European Autism Project (LEAP). We also examined neurodevelopmental differences and their potential pathophysiological mechanisms between clinical ASD subgroups, which 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), we found that ASD individuals manifested as neuroanatomical outliers within the neurotypical CT 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 the higher polygenic scores for ASD, and other psychiatric conditions, and scaled with measures of symptom severity. Differences in CT deviations were also associated with distinct sensory subgroups, especially in brain regions expressing genes involved in excitatory rather than inhibitory neurotransmission. Conclusions. Our 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.

Metadata

Statistics

DownloadsShow export options

Export as XMLJSONCSV

Activity Overview

6 month trend

246Downloads

6 month trend

201Hits

Additional statistics are available via IRStats2.

Archive Staff Only (login required)

Edit/View Item