Decomposing the Brain in Autism: Linking Behavioral Domains to Neuroanatomical Variation and Genomic Underpinnings

Hanna Seelemeyer; Caroline Gurr; Johanna Leyhausen; Lisa M Berg; Charlotte M Pretzsch; Tim Schäfer; Bassem Hermila; Christine M Freitag; Eva Loth; Bethany Oakley; Luke Mason; Jan K Buitelaar; Christian F Beckmann; Dorothea L Floris; Tony Charman; Tobias Banaschewski; Emily Jones; Thomas Bourgeron; EU-AIMS LEAP Group; Declan Murphy; Christine Ecker

doi:10.1016/j.bpsc.2024.12.003

Decomposing the Brain in Autism: Linking Behavioral Domains to Neuroanatomical Variation and Genomic Underpinnings

Biol Psychiatry Cogn Neurosci Neuroimaging. 2024 Dec 17:S2451-9022(24)00379-3. doi: 10.1016/j.bpsc.2024.12.003. Online ahead of print.

Authors

Hanna Seelemeyer¹, Caroline Gurr², Johanna Leyhausen³, Lisa M Berg³, Charlotte M Pretzsch⁴, Tim Schäfer⁵, Bassem Hermila², Christine M Freitag⁶, Eva Loth⁴, Bethany Oakley⁴, Luke Mason⁴, Jan K Buitelaar⁷, Christian F Beckmann⁷, Dorothea L Floris⁸, Tony Charman⁹, Tobias Banaschewski¹⁰, Emily Jones¹¹, Thomas Bourgeron¹²; EU-AIMS LEAP Group; Declan Murphy⁴, Christine Ecker¹³

Collaborators

EU-AIMS LEAP Group:
Jumana Ahmad, Sara Ambrosino, Bonnie Auyeung, Tobias Banaschewski, Simon Baron-Cohen, Sarah Baumeister, Christian F Beckmann, Sven Bölte, Thomas Bourgeron, Carsten Bours, Michael Brammer, Daniel Brandeis, Claudia Brogna, Yvette de Bruijn, Jan K Buitelaar, Bhismadev Chakrabarti, Tony Charman, Ineke Cornelissen, Daisy Crawley, Flavio Dell'Acqua, Guillaume Dumas, Sarah Durston, Christine Ecker, Jessica Faulkner, Vincent Frouin, Pilar Garcés, David Goyard, Lindsay Ham, Hannah Hayward, Joerg Hipp, Rosemary Holt, Mark H Johnson, Emily J H Jones, Prantik Kundu, Meng-Chuan Lai, Xavier Liogier D'ardhuy, Michael V Lombardo, Eva Loth, David J Lythgoe, René Mandl, Andre Marquand, Luke Mason, Maarten Mennes, Andreas Meyer-Lindenberg, Carolin Moessnang, Nico Bast, Declan G M Murphy, Bethany Oakley, Laurence O'Dwyer, Marianne Oldehinkel, Bob Oranje, Gahan Pandina, Antonio M Persico, Barbara Ruggeri, Amber Ruigrok, Jessica Sabet, Roberto Sacco, Antonia San José Cáceres, Emily Simonoff, Will Spooren, Julian Tillmann, Roberto Toro, Heike Tost, Jack Waldman, Steve C R Williams, Caroline Wooldridge, Marcel P Zwiers

Affiliations

¹ Department of Child and Adolescent Psychiatry, University Hospital, Goethe University, 60528 Frankfurt am Main, Germany; Brain Imaging Center, Goethe-University, 60528 Frankfurt am Main, Germany. Electronic address: [email protected].
² Department of Child and Adolescent Psychiatry, University Hospital, Goethe University, 60528 Frankfurt am Main, Germany; Brain Imaging Center, Goethe-University, 60528 Frankfurt am Main, Germany.
³ Department of Child and Adolescent Psychiatry, University Hospital, Goethe University, 60528 Frankfurt am Main, Germany; Brain Imaging Center, Goethe-University, 60528 Frankfurt am Main, Germany; Department of Biosciences, Goethe University Frankfurt, 60438 Frankfurt am Main, Germany.
⁴ Department of Forensic and Neurodevelopmental Sciences, Institute of Psychiatry, Psychology and Neuroscience, King's College, London, SE5 8AF, UK.
⁵ Fries Lab, Ernst Strüngmann Institut (ESI) for Neuroscience in Cooperation with Max Planck Society, 60528 Frankfurt, Germany.
⁶ Department of Child and Adolescent Psychiatry, University Hospital, Goethe University, 60528 Frankfurt am Main, Germany.
⁷ Department of Cognitive Neuroscience, Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen Medical Center, 6525 EN Nijmegen, The Netherlands.
⁸ Department of Cognitive Neuroscience, Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen Medical Center, 6525 EN Nijmegen, The Netherlands; Methods of Plasticity Research, Department of Psychology, University of Zurich, Zurich, Switzerland.
⁹ Department of Psychology, Institute of Psychiatry, Psychology and Neuroscience, King's College London, De Crespigny Park, Denmark Hill, London SE5 8AF, UK.
¹⁰ Child and Adolescent Psychiatry, Central Institute of Mental Health, University of Heidelberg, Medical Faculty Mannheim, J5, 68159 Mannheim, Germany; German Center for Mental Health (DZPG), partner site Mannheim-Heidelberg-Ulm, 68159 Mannheim, Germany.
¹¹ Centre for Brain and Cognitive Development, Birkbeck, University of London, 32 Torrington Square, London WC1E 7JL, UK.
¹² Institut Pasteur, Human Genetics and Cognitive Functions Unit, 25 Rue du Docteur Roux, Paris Cedex 15, France.
¹³ Department of Child and Adolescent Psychiatry, University Hospital, Goethe University, 60528 Frankfurt am Main, Germany; Brain Imaging Center, Goethe-University, 60528 Frankfurt am Main, Germany; Department of Forensic and Neurodevelopmental Sciences, Institute of Psychiatry, Psychology and Neuroscience, King's College, London, SE5 8AF, UK.

PMID: 39701384
DOI: 10.1016/j.bpsc.2024.12.003

Abstract

Background: Autism is accompanied by highly individualized patterns of neurodevelopmental differences in brain anatomy. This variability makes the neuroanatomy of autism inherently difficult to describe at the group level. Here, we examined inter-individual neuroanatomical differences using a dimensional approach that decomposed the domains of social communication and interaction (SCI), restricted and repetitive behaviors (RRB), and atypical sensory processing (ASP) within a neurodiverse study population. Moreover, we aimed to link the resulting neuroanatomical patterns to specific molecular underpinnings.

Methods: Neurodevelopmental differences in cortical thickness and surface area were correlated with SCI, RRB and ASP domain scores by regression of a General Linear Model in a large neurodiverse sample of N=288 autistic and N=140 non-autistic individuals, aged 6-30, recruited within the EU-AIMS Longitudinal European Autism Project (LEAP). The domain-specific patterns of neuroanatomical variability were subsequently correlated with cortical gene expression profiles via the Allan Human Brain Atlas.

Results: Across groups, behavioral variations in SCI, RRB and ASP were associated with interindividual differences in CT and SA in partially non-overlapping fronto-parietal, temporal, and occipital networks. These domain-specific imaging patterns were enriched for genes (i) differentially expressed in autism, (ii) mediating typical brain development, and that are (iii) associated with specific cortical cell types. Many of these genes were implicated in pathways governing synaptic structure and function.

Conclusions: Our study corroborates the close relationship between neuroanatomical variation and interindividual differences in autism-related symptoms and traits within the general framework of neurodiversity, and links domain-specific patterns of neuroanatomical differences to putative molecular underpinnings.

Keywords: MRI; autism spectrum disorder; autism symptomatology; brain structure.