Local molecular and global connectomic contributions to cross-disorder cortical abnormalities.
Journal: Nature communications
Volume: 13
Issue: 1
Year of Publication: 2022
Affiliated Institutions:
McConnell Brain Imaging Centre, Montréal Neurological Institute, McGill University, Montréal, QC, Canada.
Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Department of Radiology and Biomedical Imaging, Yale School of Medicine, New Haven, CT, , USA.
Departments of Psychiatry and Biobehavioral Sciences and Psychology, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, CA, USA.
Departments of Psychiatry and Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands.
Donders Institute for Brain, Cognition and Behavior, Radboud University, Nijmegen, The Netherlands.
Department of Psychiatry, University of California San Diego, La Jolla, CA, USA.
Department of Clinical and Experimental Epilepsy, UCL Queen Square Institute of Neurology, London, WCN BG, UK.
Centre for Youth Mental Health, The University of Melbourne, Melbourne, VIC, Australia.
Department of Psychiatry, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam Neuroscience, Amsterdam, The Netherlands.
SA MRC Unit on Risk & Resilience in Mental Disorders, Dept of Psychiatry & Neuroscience Institute, University of Cape Town, Cape Town, South Africa.
Clinical Translational Neuroscience Laboratory, Department of Psychiatry and Human Behavior, & Center for the Neurobiology of Leaning and Memory, University of California Irvine, Qureshey Research Lab, Irvine, CA, USA.
Keck School of Medicine, Imaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, University of Southern California, Los Angeles, CA, USA.
NORMENT Centre, Institute of Clinical Medicine, University of Oslo and Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.
Department of Psychiatry, Dalhousie University, Halifax, NS, Canada.
Institute of Translational Psychiatry, University of Münster, Münster, Germany & Department of Psychiatry, Jena University Hospital/Friedrich-Schiller-University Jena, Jena, Germany.
Department of Psychosis Studies & MRC Centre for Neurodevelopmental Disorders, King's College London, London, UK.
Department of Biomedical Sciences of Cells and Systems, University of Groningen, Groningen, The Netherlands.
Department of Anatomy & Neuroscience, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam Neuroscience, Amsterdam, the Netherlands.
McConnell Brain Imaging Centre, Montréal Neurological Institute, McGill University, Montréal, QC, Canada. bratislav.misic@mcgill.ca.
Abstract summary
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.
Authors & Co-authors:
Hansen Justine Y JY
Shafiei Golia G
Vogel Jacob W JW
Smart Kelly K
Bearden Carrie E CE
Hoogman Martine M
Franke Barbara B
van Rooij Daan D
Buitelaar Jan J
McDonald Carrie R CR
Sisodiya Sanjay M SM
Schmaal Lianne L
Veltman Dick J DJ
van den Heuvel Odile A OA
Stein Dan J DJ
van Erp Theo G M TGM
Ching Christopher R K CRK
Andreassen Ole A OA
Hajek Tomas T
Opel Nils N
Modinos Gemma G
Aleman André A
van der Werf Ysbrand Y
Jahanshad Neda N
Thomopoulos Sophia I SI
Thompson Paul M PM
Carson Richard E RE
Dagher Alain A
Misic Bratislav B
Study Outcome
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