Cortical patterning of abnormal morphometric similarity in psychosis is associated with brain expression of schizophrenia-related genes.
van Amelsvoort, Therese
Proceedings of the National Academy of Sciences of the United States of America
National Academy of Sciences
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Morgan, S., Seidlitz, J., Whitaker, K., Romero-Garcia, R., Clifton, N. E., Scarpazza, C., van Amelsvoort, T., et al. (2019). Cortical patterning of abnormal morphometric similarity in psychosis is associated with brain expression of schizophrenia-related genes.. Proceedings of the National Academy of Sciences of the United States of America, 116 (19), 9604-9609. https://doi.org/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 underlying 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 three prior post mortem studies of schizophrenia. We propose that this combined analysis of neuroimaging and transcriptional data provides new 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.
Brain, Nerve Net, Neural Pathways, Humans, Case-Control Studies, Psychotic Disorders, Schizophrenia, Gene Expression Regulation, Adult, Middle Aged, Female, Male, Neuroimaging
This study was supported by grants from the European Commission (PSYSCAN - Translating neuroimaging findings from research into clinical practice; ID: 603196) and the NIHR Cambridge Biomedical Research Centre (Mental Health). SEM holds a Henslow Fellowship at Lucy Cavendish College, University of Cambridge, funded by the Cambridge Philosophical Society. PEV was supported by the Medical Research Council (MR/K020706/1) and an MQ fellowship (MQF17_24) and is a Fellow of the Alan Turing Institute funded under the EPSRC grant EP/N510129/1. KJW was funded by an Alan Turing Institute Research Fellowship under EPSRC Research grant TU/A/000017. ETB is supported by a NIHR Senior Investigator Award.
EC FP7 CP (603196)
Cambridge University Hospitals NHS Foundation Trust (CUH) (146281)
Alan Turing Institute (AT/120001/005)
MQ: Transforming Mental Health (MQ17-24 Vertes)
External DOI: https://doi.org/10.1073/pnas.1820754116
This record's URL: https://www.repository.cam.ac.uk/handle/1810/291175
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