RT Journal Article
SR Electronic
T1 Molecular and connectomic vulnerability shape cross-disorder cortical abnormalities
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2022.01.21.476409
DO 10.1101/2022.01.21.476409
A1 Justine Y. Hansen
A1 Golia Shafiei
A1 Jacob W. Vogel
A1 Kelly Smart
A1 Carrie E. Bearden
A1 Martine Hoogman
A1 Barbara Franke
A1 Daan van Rooij
A1 Jan Buitelaar
A1 Carrie R. McDonald
A1 Sanjay M. Sisodiya
A1 Lianne Schmaal
A1 Dick J. Veltman
A1 Odile A. van den Heuvel
A1 Dan J. Stein
A1 Theo G. M. van Erp
A1 Christopher R. K. Ching
A1 Ole A. Andreassen
A1 Tomas Hajek
A1 Nils Opel
A1 Gemma Modinos
A1 André Aleman
A1 Ysbrand van der Werf
A1 Neda Jahanshad
A1 Sophia I. Thomopoulos
A1 Paul M. Thompson
A1 Richard E. Carson
A1 Alain Dagher
A1 Bratislav Misic
YR 2022
UL http://biorxiv.org/content/early/2022/01/21/2022.01.21.476409.abstract
AB 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 patients and N = 26 000 controls, collected using a harmonized 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 that regional molecular vulnerability and macroscale brain network architecture interact to drive the spatial patterning of cortical abnormalities in multiple disorders. 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, medial temporal lobe, precuneus, and superior parietal cortex. Collectively, our results highlight how local biological attributes and global connectivity jointly shape cross-disorder cortical abnormalities.Competing Interest StatementThe authors have declared no competing interest.