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

By Sarah E. Morgan, Jakob Seidlitz, Kirstie 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, The PSYSCAN Consortium, Petra E. VĂ©rtes, Edward T. Bullmore

Posted 19 Dec 2018
bioRxiv DOI: 10.1101/501494 (published DOI: 10.1073/pnas.1820754116)

Schizophrenia has been conceived as a disorder of brain connectivity but it is unclear how this network phenotype is related to the emerging genetics. We used morphometric similarity analysis of magnetic resonance imaging (MRI) data as a marker of inter-areal 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 (MS) in all 3 studies. There was also a replicable pattern of case-control differences in regional MS 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 MS 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 over-expressed in cortical areas with reduced MS were significantly up-regulated in a prior post mortem study of schizophrenia. We propose that this combination of neuroimaging and transcriptional data provides new insight into how previously implicated genes and proteins, as well as a number of unreported proteins in their vicinity on the protein interaction network, may interact to drive structural brain network changes in schizophrenia.

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