@article{b2169de654734c9bb7f86217ba51f366,
title = "Cortical patterning of abnormal morphometric similarity in psychosis is associated with brain expression of schizophrenia-related genes",
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.",
keywords = "dysconnectivity, psychosis, network neuroscience, morphometric similarity, Allen Human Brain Atlas, NETWORKS, RECEPTOR, POLYMORPHISMS, ORGANIZATION, METAANALYSIS, HUBS",
author = "Morgan, {Sarah E.} and Jakob Seidlitz and Whitaker, {Kirstie J.} and Rafael Romero-Garcia and Clifton, {Nicholas E.} and Cristina Scarpazza and {van Amelsvoort}, Therese and Machteld Marcelis and {van Os}, Jim and Gary Donohoe and David Mothersill and Aiden Corvin and Andrew Pocklington and Armin Raznahan and Philip McGuire and Vertes, {Petra E.} and Bullmore, {Edward T.}",
note = "Funding Information: This study was supported by European Commission Grant PSYSCAN—Translating neuroimaging findings from research into clinical practice 603196 and an National Institute for Health Research (NIHR) Cambridge Biomedical Research Center (Mental Health) Grant. The Center of Biomedical Research Excellence (COBRE) data were downloaded from the Collaborative Informatics and Neuroimaging Suite Data Exchange tool (COINS; coins.mrn.org/dx), and data collection was performed at the Mind Research Network and funded by COBRE Grant 5P20RR021938/P20GM103472 from the NIH. S.E.M. holds a Henslow Fellowship at Lucy Cavendish College, University of Cambridge that is funded by the Cambridge Philosophical Society. K.J.W. was funded by an Alan Turing Institute Research Fellowship under Engineering and Physical Sciences Research Council (EPSRC) Research Grant TU/A/000017. P.E.V. was supported by Medical Research Council Grant MR/K020706/1 and MQ: Transforming Mental Health Fellowship MQF17 24 and is a Fellow of the Alan Turing Institute funded under EPSRC Grant EP/N510129/1. E.T.B. is supported by an NIHR Senior Investigator Award. The views expressed are those of the author(s) and are not necessarily those of the National Health Service, the NIHR, or the Department of Health and Social Care. Funding Information: ACKNOWLEDGMENTS. This study was supported by European Commission Grant PSYSCAN—Translating neuroimaging findings from research into clinical practice 603196 and an National Institute for Health Research (NIHR) Cambridge Biomedical Research Center (Mental Health) Grant. The Center of Biomedical Research Excellence (COBRE) data were downloaded from the Collaborative Informatics and Neuroimaging Suite Data Exchange tool (COINS; coins.mrn.org/dx), and data collection was performed at the Mind Research Network and funded by COBRE Grant 5P20RR021938/P20GM103472 from the NIH. S.E.M. holds a Henslow Fellowship at Lucy Cavendish College, University of Cambridge that is funded by the Cambridge Philosophical Society. K.J.W. was funded by an Alan Turing Institute Research Fellowship under Engineering and Physical Sciences Research Council (EPSRC) Research Grant TU/A/000017. P.E.V. was supported by Medical Research Council Grant MR/K020706/1 and MQ: Transforming Mental Health Fellowship MQF17 24 and is a Fellow of the Alan Turing Institute funded under EPSRC Grant EP/N510129/1. E.T.B. is supported by an NIHR Senior Investigator Award. The views expressed are those of the author(s) and are not necessarily those of the National Health Service, the NIHR, or the Department of Health and Social Care. Publisher Copyright: {\textcopyright} 2019 National Academy of Sciences. All rights reserved.",
year = "2019",
month = may,
day = "7",
doi = "10.1073/pnas.1820754116",
language = "English",
volume = "116",
pages = "9604--9609",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
publisher = "National Academy of Sciences",
number = "19",
}