Cortical patterning of abnormal morphometric similarity in psychosis is associated with brain expression of schizophrenia-related genes

Sarah E. Morgan*, Jakob Seidlitz, Kirstie J. Whitaker, Rafael Romero-Garcia, Nicholas E. Clifton, Cristina Scarpazza, Therese van Amelsvoort, Machteld Marcelis, Jim van Os, Gary Donohoe, David Mothersill, Aiden Corvin, Andrew Pocklington, Armin Raznahan, Philip McGuire, Petra E. Vertes, Edward T. Bullmore

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

60 Citations (Web of Science)

Abstract

Schizophrenia has been conceived as a disorder of brain connectivity, but it is unclear how this network phenotype is related to the underlying genetics. We used morphometric similarity analysis of MRI data as a marker of interareal cortical connectivity in three prior case-control studies of psychosis: in total, n = 185 cases and n = 227 controls. Psychosis was associated with globally reduced morphometric similarity in all three studies. There was also a replicable pattern of case-control differences in regional morphometric similarity, which was significantly reduced in patients in frontal and temporal cortical areas but increased in parietal cortex. Using prior brain-wide gene expression data, we found that the cortical map of case-control differences in morphometric similarity was spatially correlated with cortical expression of a weighted combination of genes enriched for neurobiologically relevant ontology terms and pathways. In addition, genes that were normally overexpressed in cortical areas with reduced morphometric similarity were significantly up-regulated in three prior post mortem studies of schizophrenia. We propose that this combined analysis of neuroimaging and transcriptional data provides insight into how previously implicated genes and proteins as well as a number of unreported genes in their topological vicinity on the protein interaction network may drive structural brain network changes mediating the genetic risk of schizophrenia.

Original languageEnglish
Pages (from-to)9604-9609
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume116
Issue number19
DOIs
Publication statusPublished - 7 May 2019

Keywords

  • dysconnectivity
  • psychosis
  • network neuroscience
  • morphometric similarity
  • Allen Human Brain Atlas
  • NETWORKS
  • RECEPTOR
  • POLYMORPHISMS
  • ORGANIZATION
  • METAANALYSIS
  • HUBS

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