The neuroanatomical substrates of autism and ADHD and their link to putative genomic underpinnings

Lisa M. Berg*, Caroline Gurr, Johanna Leyhausen, Hanna Seelemeyer, Anke Bletsch, Tim Schaefer, Charlotte M. Pretzsch, Bethany Oakley, Eva Loth, Dorothea L. Floris, Jan K. Buitelaar, Christian F. Beckmann, Tobias Banaschewski, Tony Charman, Emily J.H. Jones, Julian Tillmann, Chris H. Chatham, Thomas Bourgeron, Jumana Ahmad, Sara AmbrosinoBonnie Auyeung, Simon Baron-Cohen, Sarah Baumeister, Sven Bölte, Carsten Bours, Michael Brammer, Daniel Brandeis, Claudia Brogna, Yvette de Bruijn, Bhismadev Chakrabarti, Ineke Cornelissen, Daisy Crawley, Flavio Dell’Acqua, Guillaume Dumas, Sarah Durston, Jessica Faulkner, Vincent Frouin, Pilar Garcés, David Goyard, Lindsay Ham, Hannah Hayward, Joerg Hipp, Rosemary Holt, Mark H. Johnson, Prantik Kundu, David J. Lythgoe, Luke Mason, Barbara Ruggeri, Emily Simonoff, Christine Ecker

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Autism spectrum disorders (ASD) are neurodevelopmental conditions accompanied by differences in brain development. Neuroanatomical differences in autism are variable across individuals and likely underpin distinct clinical phenotypes. To parse heterogeneity, it is essential to establish how the neurobiology of ASD is modulated by differences associated with co-occurring conditions, such as attention-deficit/hyperactivity disorder (ADHD). This study aimed to (1) investigate between-group differences in autistic individuals with and without co-occurring ADHD, and to (2) link these variances to putative genomic underpinnings. Methods: We examined differences in cortical thickness (CT) and surface area (SA) and their genomic associations in a sample of 533 individuals from the Longitudinal European Autism Project. Using a general linear model including main effects of autism and ADHD, and an ASD-by-ADHD interaction, we examined to which degree ADHD modulates the autism-related neuroanatomy. Further, leveraging the spatial gene expression data of the Allen Human Brain Atlas, we identified genes whose spatial expression patterns resemble our neuroimaging findings. Results: In addition to significant main effects for ASD and ADHD in fronto-temporal, limbic, and occipital regions, we observed a significant ASD-by-ADHD interaction in the left precentral gyrus and the right frontal gyrus for measures of CT and SA, respectively. Moreover, individuals with ASD + ADHD differed in CT to those without. Both main effects and the interaction were enriched for ASD—but not for ADHD-related genes. Limitations: Although we employed a multicenter design to overcome single-site recruitment limitations, our sample size of N = 25 individuals in the ADHD only group is relatively small compared to the other subgroups, which limits the generalizability of the results. Also, we assigned subjects into ADHD positive groupings according to the DSM-5 rating scale. While this is sufficient for obtaining a research diagnosis of ADHD, our approach did not take into account for how long the symptoms have been present, which is typically considered when assessing ADHD in the clinical setting. Conclusion: Thus, our findings suggest that the neuroanatomy of ASD is significantly modulated by ADHD, and that autistic individuals with co-occurring ADHD may have specific neuroanatomical underpinnings potentially mediated by atypical gene expression.

Original languageEnglish
Article number36
JournalMolecular Autism
Volume14
Issue number1
DOIs
Publication statusPublished - Dec 2023

Keywords

  • ADHD
  • ASD
  • Comorbidity
  • Imaging-genetics
  • Neurodevelopmental disorders
  • Structural MRI

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