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Novel Gyrification Networks Reveal Links with Psychiatric Risk Factors in Early Illness

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Rachele Sanfelici, Anne Ruef, Linda A. Antonucci, Nora Penzel, Aristeidis Sotiras, Mark Sen Dong, Maria Urquijo-Castro, Julian Wenzel, Lana Kambeitz-Ilankovic, Meike D. Hettwer, Stephan Ruhrmann, Katharine Chisholm, Anita Riecher-Rössler, Peter Falkai, Christos Pantelis, Raimo K.R. Salokangas, Rebekka Lencer, Alessandro Bertolino, Joseph Kambeitz, Eva Meisenzahl & 7 more Stefan Borgwardt, Paolo Brambilla, Stephen J. Wood, Rachel Upthegrove, Frauke Schultze-Lutter, Nikolaos Koutsouleris, Dominic B. Dwyer

Original languageEnglish
Pages (from-to)1625-1636
Number of pages12
JournalCerebral Cortex
Issue number8
Early online date14 Sep 2021
Accepted/In press13 Jul 2021
E-pub ahead of print14 Sep 2021
Published15 Apr 2022

Bibliographical note

Publisher Copyright: © 2021 The Author(s) 2021. Published by Oxford University Press. All rights reserved.

King's Authors


Adult gyrification provides a window into coordinated early neurodevelopment when disruptions predispose individuals to psychiatric illness. We hypothesized that the echoes of such disruptions should be observed within structural gyrification networks in early psychiatric illness that would demonstrate associations with developmentally relevant variables rather than specific psychiatric symptoms. We employed a new data-driven method (Orthogonal Projective Non-Negative Matrix Factorization) to delineate novel gyrification-based networks of structural covariance in 308 healthy controls. Gyrification within the networks was then compared to 713 patients with recent onset psychosis or depression, and at clinical high-risk. Associations with diagnosis, symptoms, cognition, and functioning were investigated using linear models. Results demonstrated 18 novel gyrification networks in controls as verified by internal and external validation. Gyrification was reduced in patients in temporal-insular, lateral occipital, and lateral fronto-parietal networks (pFDR < 0.01) and was not moderated by illness group. Higher gyrification was associated with better cognitive performance and lifetime role functioning, but not with symptoms. The findings demonstrated that gyrification can be parsed into novel brain networks that highlight generalized illness effects linked to developmental vulnerability. When combined, our study widens the window into the etiology of psychiatric risk and its expression in adulthood.

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