Résumé
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.
| Langue d'origine | English |
|---|---|
| Numéro d'article | 4682 |
| Journal | Nature Communications |
| Volume | 13 |
| Numéro de publication | 1 |
| DOI | |
| Statut de publication | Published - déc. 2022 |
Note bibliographique
Funding Information:C.R.K.C., N.J., P.M.T. received partial research support from Biogen, Inc., for research unrelated to this manuscript. J.B. has been in the past 3 years a consultant to/member of advisory board of/and/or speaker for Takeda/Shire, Roche, Medice, Angelini, Janssen, and Servier. He is not an employee of any of these companies, and not a stock shareholder of any of these companies. He has no other financial or material support, including expert testimony, patents, royalties. B.F. has received educational speaking fees from Medice GmbH. D.J.S. has received research grants and/or consultancy honoraria from Lundbeck and Sun. The remaining authors declare no competing interests.
Funding Information:
This research was undertaken thanks in part to funding from the Canada First Research Excellence Fund, awarded to McGill University for the Healthy Brains for Healthy Lives initiative. B.M. acknowledges support from the Natural Sciences and Engineering Research Council of Canada (NSERC Discovery Grant RGPIN #017-04265), the Canada Research Chairs Programme, the Brain Canada Future Leaders Fund and the Healthy Brains for Healthy Lives initiative. J.Y.H. acknowledges support from the Helmholtz International BigBrain Analytics & Learning Laboratory, the Natural Sciences and Engineering Research Council of Canada, and the Fonds de reserches de Québec. The research studies produced by the ENIGMA Working Groups would not be possible without the contributions of many researchers across the globe and the authors of this work thank all scientists who contribute to making this work possible. A full list of ENIGMA Consortium current and past members can be found here http://enigma.ini.usc.edu/ongoing/members/ . The authors acknowledge the NIH Big Data to Knowledge (BD2K) award for foundational support and consortium development (U54 EB020403 to P.M.T.) and support from NIMH R01MH116147 (P.M.T.), NIMH R01MH116147 (T.G.M.v.E.), NIMH R01 MH117601 (N.J., L.S.), NIMH R01MH085953 (C.E.B.), NIMH R21MH116473 (C.E.B.), NIMH 1U01MH119736 (C.E.B.). For a complete list of ENIGMA-related grant support please see here: http://enigma.ini.usc.edu/about-2/funding . J.B. has been supported by the EU-AIMS (European Autism Interventions) and AIMS-2-TRIALS programmes, which receive support from Innovative Medicines Initiative Joint Undertaking Grant No. 115300 and 777394, the resources of which are composed of financial contributions from the European Union’s FP7 and Horizon2020 Programmes, and from the European Federation of Pharmaceutical Industries and Associations (EFPIA) companies’ in-kind contributions, and AUTISM SPEAKS, Autistica and SFARI; and by the Horizon2020 supported programme CANDY Grant No. 847818). B.F. is supported by the European Community’s Horizon 2020 Programme (H2020/2014-2020) under grant agreements no. 667302 (CoCA), no. 728018 (Eat2beNICE), and no. 847879 (PRIME). This work was supported by a personal Veni grant to M.H. from the Netherlands Organisation for Scientific Research (NWO, grant number 91619115). C.R.M. is supported by NIH R01 NS065838; R21 NS107739. D.J.S. is supported by South African Medical Research Council. G.M. is funded by a Wellcome Trust & The Royal Society Sir Henry Dale Fellowship [202397/Z/16/Z]. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.
Publisher Copyright:
© 2022, The Author(s).
ASJC Scopus Subject Areas
- General Chemistry
- General Biochemistry,Genetics and Molecular Biology
- General
- General Physics and Astronomy
PubMed: MeSH publication types
- Journal Article
- Research Support, Non-U.S. Gov't
- Research Support, N.I.H., Extramural