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Multilevel neural gradients reflect transdiagnostic effects of major psychiatric conditions on cortical morphology

View ORCID ProfileBo-yong Park, Valeria Kebets, Sara Larivière, Meike D. Hettwer, Casey Paquola, View ORCID ProfileDaan van Rooij, Jan Buitelaar, Barbara Franke, Martine Hoogman, Lianne Schmaal, Dick J. Veltman, Odile van den Heuvel, Dan J. Stein, View ORCID ProfileOle A. Andreassen, Christopher R. K. Ching, Jessica Turner, Theo G. M. van Erp, Alan C. Evans, Alain Dagher, View ORCID ProfileSophia I. Thomopoulos, View ORCID ProfilePaul M. Thompson, View ORCID ProfileSofie L. Valk, View ORCID ProfileMatthias Kirschner, View ORCID ProfileBoris C. Bernhardt
doi: https://doi.org/10.1101/2021.10.29.466434
Bo-yong Park
1McConnell Brain Imaging Centre, Montreal Neurological Institute and Hospital, McGill University, Montreal, Quebec, Canada
2Department of Data Science, Inha University, Incheon, Republic of Korea
3Center for Neuroscience Imaging Research, Institute for Basic Science, Suwon, Republic of Korea
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  • ORCID record for Bo-yong Park
  • For correspondence: boyong.park@inha.ac.kr boris.bernhardt@mcgill.ca
Valeria Kebets
1McConnell Brain Imaging Centre, Montreal Neurological Institute and Hospital, McGill University, Montreal, Quebec, Canada
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Sara Larivière
1McConnell Brain Imaging Centre, Montreal Neurological Institute and Hospital, McGill University, Montreal, Quebec, Canada
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Meike D. Hettwer
4Forschungszentrum Julich, Germany
5Max Planck Institute for Cognitive and Brain Sciences, Leipzig, Germany
6Max Planck School of Cognition, Leipzig, Germany
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Casey Paquola
1McConnell Brain Imaging Centre, Montreal Neurological Institute and Hospital, McGill University, Montreal, Quebec, Canada
7INM-1, Forschungszentrum Julich, Germany
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Daan van Rooij
8Center for Cognitive Neuroimaging, Donders Institute for Brain, Cognition and Behavior, Radboud University, Nijmegen, The Netherlands
9Department of Psychiatry, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
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Jan Buitelaar
10Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, The Netherlands
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Barbara Franke
10Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, The Netherlands
11Department of Human Genetics & Psychiatry, Radboud university medical center, Nijmegen, The Netherlands
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Martine Hoogman
10Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, The Netherlands
11Department of Human Genetics & Psychiatry, Radboud university medical center, Nijmegen, The Netherlands
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Lianne Schmaal
12Centre for Youth Mental Health, The University of Melbourne, Melbourne, Australia
13Orygen, Parkville, Australia
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Dick J. Veltman
14Departments of Psychiatry and Anatomy and Neuroscience, Amsterdam University Medical Centers, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
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Odile van den Heuvel
14Departments of Psychiatry and Anatomy and Neuroscience, Amsterdam University Medical Centers, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
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Dan J. Stein
15SA Medical Research Council Unit on Risk & Resilience in Mental Disorders, Dept of Psychiatry and Mental Health, University of Cape Town, Cape Town, South Africa
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Ole A. Andreassen
16NORMENT Centre, Division of Mental Health and Addiction, Oslo University Hospital &Institute of Clinical Medicine, University of Oslo, Oslo, Norway
17KG Jebsen Centre for Neurodevelopment, Institute of Clinical Medicine, University of Oslo, Oslo, Norway
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Christopher R. K. Ching
18Imaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, USA
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Jessica Turner
19Department of Psychology, Georgia State University, USA
20Tri-institutional Center for Translational Research in Neuroimaging and Data Science (TReNDS), Georgia State University, Georgia Institute of Technology and Emory University, USA
21Neuroscience Institute, Georgia State University, USA
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Theo G. M. van Erp
22Clinical Translational Neuroscience Laboratory, Department of Psychiatry and Human Behavior, University of California Irvine, Irvine, California, USA
23Center for the Neurobiology of Learning and Memory, University of California Irvine, Irvine, California, USA
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Alan C. Evans
1McConnell Brain Imaging Centre, Montreal Neurological Institute and Hospital, McGill University, Montreal, Quebec, Canada
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Alain Dagher
1McConnell Brain Imaging Centre, Montreal Neurological Institute and Hospital, McGill University, Montreal, Quebec, Canada
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Sophia I. Thomopoulos
24Imaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, Los Angeles, California, United States of America
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Paul M. Thompson
24Imaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, Los Angeles, California, United States of America
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Sofie L. Valk
4Forschungszentrum Julich, Germany
5Max Planck Institute for Cognitive and Brain Sciences, Leipzig, Germany
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Matthias Kirschner
1McConnell Brain Imaging Centre, Montreal Neurological Institute and Hospital, McGill University, Montreal, Quebec, Canada
25Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zurich, Switzerland
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Boris C. Bernhardt
1McConnell Brain Imaging Centre, Montreal Neurological Institute and Hospital, McGill University, Montreal, Quebec, Canada
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  • ORCID record for Boris C. Bernhardt
  • For correspondence: boyong.park@inha.ac.kr boris.bernhardt@mcgill.ca
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Abstract

It is increasingly recognized that multiple psychiatric conditions are underpinned by shared neural pathways, affecting similar brain systems. Here, we assessed i) shared dimensions of alterations in cortical morphology across six major psychiatric conditions (autism spectrum disorder, attention deficit/hyperactivity disorder, major depression, obsessive-compulsive disorder, bipolar disorder, schizophrenia) and ii) carried out a multiscale neural contextualization, by cross-referencing shared anomalies against cortical myeloarchitecture and cytoarchitecture, as well as connectome and neurotransmitter organization. Pooling disease-related effects on MRI-based cortical thickness measures across six ENIGMA working groups, including a total of 28,546 participants (12,876 patients and 15,670 controls), we computed a shared disease dimension on cortical morphology using principal component analysis that described a sensory-fugal pattern with paralimbic regions showing the most consistent abnormalities across conditions. The shared disease dimension was closely related to cortical gradients of microstructure and intrinsic connectivity, as well as neurotransmitter systems, specifically serotonin and dopamine. Our findings embed the shared effects of major psychiatric conditions on brain structure in multiple scales of brain organization and may provide novel insights into neural mechanisms into transdiagnostic vulnerability.

Competing Interest Statement

Ole A. Andreassen received speaker's honorarium from Lundbeck and Sunovion, Consultant to HealthLytix. Paul M. Thompson received grant support from Biogen, Inc., and consulting payments from Kairos Venture Capital, for work unrelated to the current manuscript. Other authors declare no conflicts of interest.

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-NC-ND 4.0 International license.
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Posted November 02, 2021.
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Multilevel neural gradients reflect transdiagnostic effects of major psychiatric conditions on cortical morphology
Bo-yong Park, Valeria Kebets, Sara Larivière, Meike D. Hettwer, Casey Paquola, Daan van Rooij, Jan Buitelaar, Barbara Franke, Martine Hoogman, Lianne Schmaal, Dick J. Veltman, Odile van den Heuvel, Dan J. Stein, Ole A. Andreassen, Christopher R. K. Ching, Jessica Turner, Theo G. M. van Erp, Alan C. Evans, Alain Dagher, Sophia I. Thomopoulos, Paul M. Thompson, Sofie L. Valk, Matthias Kirschner, Boris C. Bernhardt
bioRxiv 2021.10.29.466434; doi: https://doi.org/10.1101/2021.10.29.466434
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Multilevel neural gradients reflect transdiagnostic effects of major psychiatric conditions on cortical morphology
Bo-yong Park, Valeria Kebets, Sara Larivière, Meike D. Hettwer, Casey Paquola, Daan van Rooij, Jan Buitelaar, Barbara Franke, Martine Hoogman, Lianne Schmaal, Dick J. Veltman, Odile van den Heuvel, Dan J. Stein, Ole A. Andreassen, Christopher R. K. Ching, Jessica Turner, Theo G. M. van Erp, Alan C. Evans, Alain Dagher, Sophia I. Thomopoulos, Paul M. Thompson, Sofie L. Valk, Matthias Kirschner, Boris C. Bernhardt
bioRxiv 2021.10.29.466434; doi: https://doi.org/10.1101/2021.10.29.466434

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