Local molecular and global connectomic contributions to cross-disorder cortical abnormalities.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
10 08 2022
10 08 2022
Historique:
received:
24
01
2022
accepted:
28
07
2022
entrez:
10
8
2022
pubmed:
11
8
2022
medline:
13
8
2022
Statut:
epublish
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.
Identifiants
pubmed: 35948562
doi: 10.1038/s41467-022-32420-y
pii: 10.1038/s41467-022-32420-y
pmc: PMC9365855
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
4682Subventions
Organisme : NIMH NIH HHS
ID : U01 MH119736
Pays : United States
Organisme : NINDS NIH HHS
ID : R21 NS107739
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001863
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH116147
Pays : United States
Organisme : Medical Research Council
ID : MR/N026063/1
Pays : United Kingdom
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 202397/Z/16/Z
Pays : United Kingdom
Organisme : NIMH NIH HHS
ID : R21 MH116473
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH085953
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS122827
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS065838
Pays : United States
Organisme : NIBIB NIH HHS
ID : U54 EB020403
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH117601
Pays : United States
Informations de copyright
© 2022. The Author(s).
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