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dc.contributor.authorRomero-Garcia, Rafael
dc.contributor.authorSeidlitz, Jakob
dc.contributor.authorWhitaker, Kirstie
dc.contributor.authorMorgan, Sarah
dc.contributor.authorFonagy, Peter
dc.contributor.authorDolan, Raymond J
dc.contributor.authorJones, Peter B
dc.contributor.authorGoodyer, Ian
dc.contributor.authorSuckling, John
dc.contributor.authorNSPN Consortium
dc.contributor.authorVértes, Petra E
dc.contributor.authorBullmore, Edward
dc.date.accessioned2019-12-11T11:15:43Z
dc.date.available2019-12-11T11:15:43Z
dc.date.issued2020-08-01
dc.identifier.issn0006-3223
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/299689
dc.description.abstractBACKGROUND: Genetic risk is thought to drive clinical variation on a spectrum of schizophrenia-like traits, but the underlying changes in brain structure that mechanistically link genomic variation to schizotypal experience and behavior are unclear. METHODS: We assessed schizotypy using a self-reported questionnaire and measured magnetization transfer as a putative microstructural magnetic resonance imaging marker of intracortical myelination in 68 brain regions in 248 healthy young people (14-25 years of age). We used normative adult brain gene expression data and partial least squares analysis to find the weighted gene expression pattern that was most colocated with the cortical map of schizotypy-related magnetization. RESULTS: Magnetization was significantly correlated with schizotypy in the bilateral posterior cingulate cortex and precuneus (and for disorganized schizotypy, also in medial prefrontal cortex; all false discovery rate-corrected ps < .05), which are regions of the default mode network specialized for social and memory functions. The genes most positively weighted on the whole-genome expression map colocated with schizotypy-related magnetization were enriched for genes that were significantly downregulated in two prior case-control histological studies of brain gene expression in schizophrenia. Conversely, the most negatively weighted genes were enriched for genes that were transcriptionally upregulated in schizophrenia. Positively weighted (downregulated) genes were enriched for neuronal, specifically interneuronal, affiliations and coded a network of proteins comprising a few highly interactive "hubs" such as parvalbumin and calmodulin. CONCLUSIONS: Microstructural magnetic resonance imaging maps of intracortical magnetization can be linked to both the behavioral traits of schizotypy and prior histological data on dysregulated gene expression in schizophrenia.
dc.format.mediumPrint-Electronic
dc.languageeng
dc.publisherElsevier BV
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectNSPN Consortium
dc.subjectBrain
dc.subjectHumans
dc.subjectMagnetic Resonance Imaging
dc.subjectBrain Mapping
dc.subjectSchizotypal Personality Disorder
dc.subjectSchizophrenia
dc.subjectAdolescent
dc.subjectAdult
dc.titleSchizotypy-Related Magnetization of Cortex in Healthy Adolescence Is Colocated With Expression of Schizophrenia-Related Genes.
dc.typeArticle
prism.endingPage259
prism.issueIdentifier3
prism.publicationDate2020
prism.publicationNameBiol Psychiatry
prism.startingPage248
prism.volume88
dc.identifier.doi10.17863/CAM.46759
dcterms.dateAccepted2019-12-03
rioxxterms.versionofrecord10.1016/j.biopsych.2019.12.005
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2020-08
dc.contributor.orcidSeidlitz, Jakob [0000-0002-8164-7476]
dc.contributor.orcidWhitaker, Kirstie [0000-0001-8498-4059]
dc.contributor.orcidMorgan, Sarah [0000-0002-1261-5884]
dc.contributor.orcidGoodyer, Ian [0000-0001-9183-0373]
dc.contributor.orcidSuckling, John [0000-0002-5098-1527]
dc.contributor.orcidBullmore, Edward [0000-0002-8955-8283]
dc.identifier.eissn1873-2402
rioxxterms.typeJournal Article/Review
pubs.funder-project-idWellcome Trust (095844/Z/11/Z)
pubs.funder-project-idGuarantors of Brain (unknown)
cam.orpheus.successThu Jan 30 10:34:08 GMT 2020 - Embargo updated
rioxxterms.freetoread.startdate2100-01-01


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Attribution 4.0 International
Except where otherwise noted, this item's licence is described as Attribution 4.0 International