PT  - JOURNAL ARTICLE
AU  - Xiaolong Zhang
AU  - Urs Braun
AU  - Anais Harneit
AU  - Zhenxiang Zang
AU  - Lena S. Geiger
AU  - Richard F. Betzel
AU  - Junfang Chen
AU  - Janina Schweiger
AU  - Kristina Schwarz
AU  - Jonathan Rochus Reinwald
AU  - Stefan Fritze
AU  - Stephanie Witt
AU  - Marcella Rietschel
AU  - Markus M. Nöthen
AU  - Franziska Degenhardt
AU  - Emanuel Schwarz
AU  - Dusan Hirjak
AU  - Andreas Meyer-Lindenberg
AU  - Danielle S. Bassett
AU  - Heike Tost
TI  - Generative network models identify biological mechanisms of altered structural brain connectivity in schizophrenia
AID  - 10.1101/604322
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 604322
4099  - http://biorxiv.org/content/early/2019/04/10/604322.short
4100  - http://biorxiv.org/content/early/2019/04/10/604322.full
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.