Multiscale 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 A. van den Heuvel, Dan J. Stein, Ole A. Andreassen, Christopher R. K. Ching, Jessica A. Turner, Theo G. M. van Erp, Alan C. Evans, Alain Dagher, Sophia I. ThomopoulosPaul M. Thompson, Sofie L. Valk, Matthias Kirschner, Boris C. Bernhardt

Research output: Contribution to JournalArticleAcademicpeer-review

Abstract

It is increasingly recognized that multiple psychiatric conditions are underpinned by shared neural pathways, affecting similar brain systems. Here, we carried out a multiscale neural contextualization of shared alterations of cortical morphology across six major psychiatric conditions (autism spectrum disorder, attention deficit/hyperactivity disorder, major depression disorder, obsessive-compulsive disorder, bipolar disorder, and schizophrenia). Our framework cross-referenced shared morphological anomalies with respect to 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 identified a cortex-wide dimension of morphological changes that described a sensory-fugal pattern, with paralimbic regions showing the most consistent alterations across conditions. The shared disease dimension was closely related to cortical gradients of microstructure as well as neurotransmitter axes, specifically cortex-wide variations in serotonin and dopamine. Multiple sensitivity analyses confirmed robustness with respect to slight variations in analytical choices. Our findings embed shared effects of common psychiatric conditions on brain structure in multiple scales of brain organization, and may provide insights into neural mechanisms of transdiagnostic vulnerability.
Original languageEnglish
Article number1024
JournalCommunications biology
Volume5
Issue number1
DOIs
Publication statusPublished - 1 Dec 2022
Externally publishedYes

Funding

The authors would like to express their gratitude to the open science initiatives that made this work possible: (i) The ENIGMA-Epilepsy consortium and, in particular, the ASD, ADHD, MDD, OCD, BD, and SCZ working groups ( http://enigma.ini.usc.edu/ongoing/ ) and (ii) The Human Connectome Project (Principal Investigators: David Van Essen and Kamil Ugurbil; 1U54MH091657) funded by the 16 NIH Institutes and Centers that support the NIH Blueprint for Neuroscience Research; and by the McDonnell Center for Systems Neuroscience at Washington University. Bo-yong Park was funded by the National Research Foundation of Korea (NRF-2021R1F1A1052303 and NRF-2022R1A5A7033499), Institute for Information and Communications Technology Planning and Evaluation (IITP) funded by the Korean Government (MSIT) (No. 2022-0-00448, Deep Total Recall: Continual Learning for Human-Like Recall of Artificial Neural Networks; No. 2020-0-01389, Artificial Intelligence Convergence Research Center (Inha University); No. RS-2022-00155915, Artificial Intelligence Convergence Innovation Human Resources Development (Inha University); No. 2021-0-02068, Artificial Intelligence Innovation Hub), and Institute for Basic Science (IBS-R015-D1). Valeria Kebets was funded by the Quebec Autism Research Training Fellowship of the Transforming Autism Care Consortium (TACC). Sara Larivière was funded by the Canadian Institutes of Health Research (CIHR). Meike D. Hettwer was funded by the Max Planck Society and the German Federal Ministry of Education and Research (BMBF). Martine Hoogman is supported by a personal Veni grant from the Netherlands Organization for Scientific Research (NWO, grant number 91619115). Lianne Schmaal was funded by NHMRC Career Development Fellowship (1140764), National Institute of Mental Health of the National Institutes of Health R01MH117601. Ole A. Andreassen was funded by Research Council of Norway (#223273, #283798), KG Jebsen Stiftelsen. Dan J Stein is funded by the SA MRC. Dr. Matthias Kirschner acknowledges support from the National Bank Fellowship (McGill University) and the Swiss National Foundation (P2SKP3_178175). Jessica Turner was funded by the National Institutes of Health (NIH 5R01MH121246). Paul Thompson and Sophia Thomopoulos are funded in part by the US National Institutes of Health, under grants R01MH116147, R01MH111671, R01AG058854, RF1MH123163, and U54 EB020403. Boris C. Bernhardt acknowledges research support from the National Science and Engineering Research Council of Canada (NSERC Discovery-1304413), the CIHR (FDN-154298, PJT), SickKids Foundation (NI17-039), Azrieli Center for Autism Research (ACAR-TACC), BrainCanada, Fonds de la Recherche du Québec – Santé (FRQ-S), and the Tier-2 Canada Research Chairs program. Alan Evans, Boris C. Bernhardt, and Casey Paquola were funded in part by Helmholtz Association’s Initiative and Networking Fund under the Helmholtz International Lab grant agreement InterLabs-0015, and the Canada First Research Excellence Fund (CFREF Competition 2, 2015-2016) awarded to the Healthy Brains, Healthy Lives initiative at McGill University, through the Helmholtz International BigBrain Analytics and Learning Laboratory (HIBALL). 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. The remaining authors declare no competing interests.

FundersFunder number
ACAR-TACC
Artificial Intelligence Convergence Innovation Human Resources Development2021-0-02068
Artificial Intelligence Convergence Research Center
Artificial Intelligence Innovation Hub
CFREF Competition 2
Helmholtz International BigBrain Analytics and Learning Laboratory
Helmholtz International LabInterLabs-0015
Institute for Information and Communications Technology Planning and Evaluation
National Bank
SA MRC
SickKids FoundationNI17-039
Tier-2 Canada Research Chairs
National Institutes of HealthR01MH117601
National Institute of Mental HealthRF1MH123163
NIH Blueprint for Neuroscience Research
Biogen
McGill University
Fondation Brain Canada
McDonnell Center for Systems Neuroscience
Centre Azrieli de recherche sur l'autisme, Institut et Hôpital Neurologiques de Montréal
Canadian Institutes of Health Research
Natural Sciences and Engineering Research Council of CanadaFDN-154298
Fonds de Recherche du Québec - Santé
National Health and Medical Research Council1140764
Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen ForschungP2SKP3_178175, R01MH116147, R01AG058854, 5R01MH121246, U54 EB020403, R01MH111671
Bundesministerium für Bildung und Forschung
Inha UniversityRS-2022-00155915
Nederlandse Organisatie voor Wetenschappelijk Onderzoek91619115
Ministry of Science, ICT and Future Planning2022-0-00448, 2020-0-01389
Korea National Institute of Health
National Research Foundation of KoreaNRF-2021R1F1A1052303, NRF-2022R1A5A7033499
Max-Planck-Gesellschaft
Norges forskningsråd223273, 283798
Helmholtz Association
Institute for Information and Communications Technology Promotion
Institute for Basic ScienceIBS-R015-D1
Canada First Research Excellence Fund

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