RT Journal Article
SR Electronic
T1 Generative network models identify biological mechanisms of altered structural brain connectivity in schizophrenia
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 604322
DO 10.1101/604322
A1 Xiaolong Zhang
A1 Urs Braun
A1 Anais Harneit
A1 Zhenxiang Zang
A1 Lena S. Geiger
A1 Richard F. Betzel
A1 Junfang Chen
A1 Janina Schweiger
A1 Kristina Schwarz
A1 Jonathan Rochus Reinwald
A1 Stefan Fritze
A1 Stephanie Witt
A1 Marcella Rietschel
A1 Markus M. Nöthen
A1 Franziska Degenhardt
A1 Emanuel Schwarz
A1 Dusan Hirjak
A1 Andreas Meyer-Lindenberg
A1 Danielle S. Bassett
A1 Heike Tost
YR 2019
UL http://biorxiv.org/content/early/2019/04/10/604322.abstract
AB Background Alterations in the structural connectome of schizophrenia patients have been widely characterized, but the mechanisms leading to those alterations remain largely unknown. Generative network models have recently been introduced as a tool to test the biological underpinnings of the formation of altered structural brain networks.Methods We evaluated different generative network models to investigate the formation of structural brain networks in healthy controls (n=152), schizophrenia patients (n=66) and their unaffected first-degree relatives (n=32), and we identified spatial and topological factors contributing to network formation. We further investigated the association of these factors to cognition and to polygenic risk for schizophrenia.Results Structural brain networks can be best accounted for by a two-factor model combining spatial constraints and topological neighborhood structure. The same wiring model explained brain network formation for all groups analyzed. However, relatives and schizophrenia patients exhibited significantly lower spatial constraints and lower topological facilitation compared to healthy controls. The model parameter for spatial constraint was correlated with the polygenic risk for schizophrenia and predicted reduced cognitive performance.Conclusions Our results identify spatial constraints and local topological structure as two interrelated mechanisms contributing to normal brain development as well as altered connectomes in schizophrenia. Spatial constraints were linked to the genetic risk for schizophrenia and general cognitive functioning, thereby providing insights into their biological basis and behavioral relevance.