Local molecular and global connectomic contributions to cross-disorder cortical abnormalities

Justine Y. Hansen, Golia Shafiei, Jacob W. Vogel, Kelly Smart, Carrie E. Bearden, Martine Hoogman, Barbara Franke, Daan Rooij, Jan Buitelaar, Carrie R. McDonald, Sanjay M. Sisodiya, Lianne Schmaal, Dick J. Veltman, Odile A. Heuvel, Dan J. Stein, Theo G. M. Erp, Christopher R. K. Ching, Ole A. Andreassen, Tomas Hajek, Nils Opel, Gemma Modinos, André Aleman, Ysbrand Werf, Neda Jahanshad, Sophia I. Thomopoulos, Paul M. Thompson, Richard E. Carson, Alain Dagher and Bratislav Misic ()
Additional contact information
Justine Y. Hansen: McGill University
Golia Shafiei: McGill University
Jacob W. Vogel: University of Pennsylvania
Kelly Smart: Yale School of Medicine
Carrie E. Bearden: University of California
Martine Hoogman: Radboud University Medical Center
Barbara Franke: Radboud University Medical Center
Daan Rooij: Radboud University
Jan Buitelaar: Radboud University
Carrie R. McDonald: University of California San Diego
Sanjay M. Sisodiya: UCL Queen Square Institute of Neurology
Lianne Schmaal: The University of Melbourne
Dick J. Veltman: Vrije Universiteit Amsterdam, Amsterdam Neuroscience
Odile A. Heuvel: Vrije Universiteit Amsterdam, Amsterdam Neuroscience
Dan J. Stein: University of Cape Town
Theo G. M. Erp: University of California Irvine, 309 Qureshey Research Lab
Christopher R. K. Ching: University of Southern California
Ole A. Andreassen: University of Oslo and Division of Mental Health and Addiction, Oslo University Hospital
Tomas Hajek: Dalhousie University
Nils Opel: Jena University Hospital/Friedrich-Schiller-University Jena
Gemma Modinos: King’s College London
André Aleman: University of Groningen
Ysbrand Werf: Vrije Universiteit Amsterdam, Amsterdam Neuroscience
Neda Jahanshad: University of Southern California
Sophia I. Thomopoulos: University of Southern California
Paul M. Thompson: University of Southern California
Richard E. Carson: Yale School of Medicine
Alain Dagher: McGill University
Bratislav Misic: McGill University

Nature Communications, 2022, vol. 13, issue 1, 1-17

Abstract: Abstract Numerous brain disorders demonstrate structural brain abnormalities, which are thought to arise from molecular perturbations or connectome miswiring. The unique and shared contributions of these molecular and connectomic vulnerabilities to brain disorders remain unknown, and has yet to be studied in a single multi-disorder framework. Using MRI morphometry from the ENIGMA consortium, we construct maps of cortical abnormalities for thirteen neurodevelopmental, neurological, and psychiatric disorders from N = 21,000 participants and N = 26,000 controls, collected using a harmonised processing protocol. We systematically compare cortical maps to multiple micro-architectural measures, including gene expression, neurotransmitter density, metabolism, and myelination (molecular vulnerability), as well as global connectomic measures including number of connections, centrality, and connection diversity (connectomic vulnerability). We find a relationship between molecular vulnerability and white-matter architecture that drives cortical disorder profiles. Local attributes, particularly neurotransmitter receptor profiles, constitute the best predictors of both disorder-specific cortical morphology and cross-disorder similarity. Finally, we find that cross-disorder abnormalities are consistently subtended by a small subset of network epicentres in bilateral sensory-motor, inferior temporal lobe, precuneus, and superior parietal cortex. Collectively, our results highlight how local molecular attributes and global connectivity jointly shape cross-disorder cortical abnormalities.

Date: 2022
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DOI: 10.1038/s41467-022-32420-y

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