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

Morgan, S. E.; Seidlitz, J.; Whitaker, K.; Romero-Garcia, R.; Clifton, N. E.; Scarpazza, C.; van Amelsvoort, T.; Marcelis, M.; van Os, J.; Donohoe, G.; Mothersill, D.; Corvin, A.; Pocklington, A.; Raznahan, A.; McGuire, P.; The PSYSCAN Consortium,; Vertes, P. E.; Bullmore, E. T.

doi:10.1101/501494

bioRxiv · 10.1101/501494

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

Morgan, S. E.·Seidlitz, J.·Whitaker, K.·Romero-Garcia, R.·Clifton, N. E.·Scarpazza, C.·van Amelsvoort, T.·Marcelis, M.·van Os, J.·Donohoe, G.·Mothersill, D.·Corvin, A.·Pocklington, A.·Raznahan, A.·McGuire, P.·The PSYSCAN Consortium,·Vertes, P. E.·Bullmore, E. T.

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Abstract

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 neu-robiologically 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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Morgan, S. E., Seidlitz, J., Whitaker, K., Romero-Garcia, R., Clifton, N. E., Scarpazza, C., van Amelsvoort, T., Marcelis, M., van Os, J., Donohoe, G., Mothersill, D., Corvin, A., Pocklington, A., Raznahan, A., McGuire, P., The PSYSCAN Consortium,, Vertes, P. E., Bullmore, E. T.. 2018-12-19. Cortical patterning of abnormal morphometric similarity in psychosis is associated with brain expression of schizophrenia related genes. https://doi.org/10.1101/501494

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