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Molecular and connectomic vulnerability shape cross-disorder cortical abnormalities

View ORCID ProfileJustine Y. Hansen, View ORCID ProfileGolia Shafiei, View ORCID ProfileJacob W. Vogel, View ORCID ProfileKelly Smart, Carrie E. Bearden, View ORCID ProfileMartine Hoogman, View ORCID ProfileBarbara Franke, View ORCID ProfileDaan van Rooij, View ORCID ProfileJan Buitelaar, Carrie R. McDonald, View ORCID ProfileSanjay M. Sisodiya, View ORCID ProfileLianne Schmaal, View ORCID ProfileDick J. Veltman, View ORCID ProfileOdile A. van den Heuvel, View ORCID ProfileDan J. Stein, View ORCID ProfileTheo G. M. van Erp, View ORCID ProfileChristopher R. K. Ching, View ORCID ProfileOle A. Andreassen, View ORCID ProfileTomas Hajek, View ORCID ProfileNils Opel, View ORCID ProfileGemma Modinos, View ORCID ProfileAndré Aleman, View ORCID ProfileYsbrand van der Werf, View ORCID ProfileNeda Jahanshad, View ORCID ProfileSophia I. Thomopoulos, View ORCID ProfilePaul M. Thompson, Richard E. Carson, View ORCID ProfileAlain Dagher, View ORCID ProfileBratislav Misic
doi: https://doi.org/10.1101/2022.01.21.476409
Justine Y. Hansen
1McConnell Brain Imaging Centre, Montréal Neurological Institute, McGill University, Montréal, Canada
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Golia Shafiei
1McConnell Brain Imaging Centre, Montréal Neurological Institute, McGill University, Montréal, Canada
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Jacob W. Vogel
2Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
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Kelly Smart
3Department of Radiology and Biomedical Imaging, Yale School of Medicine, New Haven, CT 06520, USA
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Carrie E. Bearden
4Departments of Psychiatry and Biobehavioral Sciences and Psychology, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, CA, USA
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Martine Hoogman
5Departments of Psychiatry and Human Genetics, Radboud University Medical Center, Nijmegen, the Netherlands
6Donders Institute for Brain, Cognition and Behavior, Radboud University, Nijmegen, The Netherlands
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Barbara Franke
5Departments of Psychiatry and Human Genetics, Radboud University Medical Center, Nijmegen, the Netherlands
6Donders Institute for Brain, Cognition and Behavior, Radboud University, Nijmegen, The Netherlands
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Daan van Rooij
6Donders Institute for Brain, Cognition and Behavior, Radboud University, Nijmegen, The Netherlands
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Jan Buitelaar
6Donders Institute for Brain, Cognition and Behavior, Radboud University, Nijmegen, The Netherlands
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Carrie R. McDonald
7Department of Psychiatry, University of California San Diego, La Jolla, CA, USA
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Sanjay M. Sisodiya
8Department of Clinical and Experimental Epilepsy, UCL Queen Square Institute of Neurology, London, UK
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Lianne Schmaal
9Centre for Youth Mental Health, The University of Melbourne, Melbourne, Australia
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Dick J. Veltman
10Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam Neuroscience, Amsterdam, the Netherlands
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Odile A. van den Heuvel
10Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam Neuroscience, Amsterdam, the Netherlands
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Dan J. Stein
11SA MRC Unit on Risk & Resilience in Mental Disorders, Dept of Psychiatry & Neuroscience Institute, University of Cape Town, Cape Town, South Africa
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Theo G. M. van Erp
12Clinical Translational Neuroscience Laboratory, Department of Psychiatry and Human Behavior, & Center for the Neurobiology of Leaning and Memory, University of California Irvine, 309 Qureshey Research Lab, Irvine, CA, USA
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Christopher R. K. Ching
13Keck School of Medicine, Imaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, University of Southern California, Los Angeles, CA, USA
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Ole A. Andreassen
14NORMENT Centre, Institute of Clinical Medicine, University of Oslo and Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway
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Tomas Hajek
15Department of Psychiatry, Dalhousie University, Halifax, NS, Canada
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Nils Opel
16Institute of Translational Psychiatry, University of Münster, Münster, Germany & Department of Psychiatry, Jena University Hospital/Friedrich-Schiller-University Jena, Jena, Germany
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Gemma Modinos
17Department of Psychosis Studies & MRC Centre for Neurodevelopmental Disorders, King’s College London, London, UK
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André Aleman
18Department of Biomedical Sciences of Cells and Systems, University of Groningen, Groningen, the Netherlands
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Ysbrand van der Werf
10Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam Neuroscience, Amsterdam, the Netherlands
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Neda Jahanshad
13Keck School of Medicine, Imaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, University of Southern California, Los Angeles, CA, USA
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Sophia I. Thomopoulos
13Keck School of Medicine, Imaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, University of Southern California, Los Angeles, CA, USA
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Paul M. Thompson
13Keck School of Medicine, Imaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, University of Southern California, Los Angeles, CA, USA
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Richard E. Carson
3Department of Radiology and Biomedical Imaging, Yale School of Medicine, New Haven, CT 06520, USA
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Alain Dagher
1McConnell Brain Imaging Centre, Montréal Neurological Institute, McGill University, Montréal, Canada
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Bratislav Misic
1McConnell Brain Imaging Centre, Montréal Neurological Institute, McGill University, Montréal, Canada
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  • For correspondence: bratislav.misic@mcgill.ca
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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 patients and N = 26 000 controls, collected using a harmonized 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 that regional molecular vulnerability and macroscale brain network architecture interact to drive the spatial patterning of cortical abnormalities in multiple disorders. 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, medial temporal lobe, precuneus, and superior parietal cortex. Collectively, our results highlight how local biological attributes and global connectivity jointly shape cross-disorder cortical abnormalities.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • ↵* bratislav.misic{at}mcgill.ca

  • https://github.com/netneurolab/hansen_crossdisorder_vulnerability

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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Molecular and connectomic vulnerability shape cross-disorder cortical abnormalities
Justine Y. Hansen, Golia Shafiei, Jacob W. Vogel, Kelly Smart, Carrie E. Bearden, Martine Hoogman, Barbara Franke, Daan van Rooij, Jan Buitelaar, Carrie R. McDonald, Sanjay M. Sisodiya, Lianne Schmaal, Dick J. Veltman, Odile A. van den Heuvel, Dan J. Stein, Theo G. M. van Erp, Christopher R. K. Ching, Ole A. Andreassen, Tomas Hajek, Nils Opel, Gemma Modinos, André Aleman, Ysbrand van der Werf, Neda Jahanshad, Sophia I. Thomopoulos, Paul M. Thompson, Richard E. Carson, Alain Dagher, Bratislav Misic
bioRxiv 2022.01.21.476409; doi: https://doi.org/10.1101/2022.01.21.476409
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Molecular and connectomic vulnerability shape cross-disorder cortical abnormalities
Justine Y. Hansen, Golia Shafiei, Jacob W. Vogel, Kelly Smart, Carrie E. Bearden, Martine Hoogman, Barbara Franke, Daan van Rooij, Jan Buitelaar, Carrie R. McDonald, Sanjay M. Sisodiya, Lianne Schmaal, Dick J. Veltman, Odile A. van den Heuvel, Dan J. Stein, Theo G. M. van Erp, Christopher R. K. Ching, Ole A. Andreassen, Tomas Hajek, Nils Opel, Gemma Modinos, André Aleman, Ysbrand van der Werf, Neda Jahanshad, Sophia I. Thomopoulos, Paul M. Thompson, Richard E. Carson, Alain Dagher, Bratislav Misic
bioRxiv 2022.01.21.476409; doi: https://doi.org/10.1101/2022.01.21.476409

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