Schizotypy-Related Magnetization of Cortex in Healthy Adolescence Is Colocated With Expression of Schizophrenia-Related Genes
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. We assessed schizotypy using a self-reported questionnaire and...
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| Veröffentlicht in: | Biological psychiatry (1969) 2020-08, Vol.88 (3), p.248-259 |
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| creator | Romero-Garcia, Rafael Seidlitz, Jakob Whitaker, Kirstie J. Morgan, Sarah E. Fonagy, Peter Dolan, Raymond J. Jones, Peter B. Goodyer, Ian M. Suckling, John Bullmore, Edward Dolan, Raymond Goodyer, Ian Fonagy, Peter Jones, Peter Vaghi, Matilde Moutoussis, Michael Hauser, Tobias Neufeld, Sharon Romero-Garcia, Rafael St Clair, Michelle Whitaker, Kirstie Inkster, Becky Prabhu, Gita Ooi, Cinly Toseeb, Umar Widmer, Barry Bhatti, Junaid Villis, Laura Alrumaithi, Ayesha Birt, Sarah Bowler, Aislinn Cleridou, Kalia Dadabhoy, Hina Davies, Emma Firkins, Ashlyn Granville, Sian Harding, Elizabeth Hopkins, Alexandra Isaacs, Daniel King, Janchai Kokorikou, Danae Maurice, Christina McIntosh, Cleo Memarzia, Jessica Mills, Harriet O’Donnell, Ciara Pantaleone, Sara Scott, Jenny Fearon, Pasco Suckling, John Harmelen, Anne-Laura van Kievit, Rogier Vértes, Petra Vértes, Petra E. Bullmore, Edward T. |
| description | 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.
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.
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 |
| doi_str_mv | 10.1016/j.biopsych.2019.12.005 |
| format | Article |
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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.
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.
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.</description><identifier>ISSN: 0006-3223</identifier><identifier>ISSN: 1873-2402</identifier><identifier>EISSN: 1873-2402</identifier><identifier>DOI: 10.1016/j.biopsych.2019.12.005</identifier><identifier>PMID: 32029217</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Adolescence ; Adolescent ; Adult ; Allen Human Brain Atlas ; Brain - diagnostic imaging ; Brain Mapping ; Development ; Fast-spiking GABAergic interneurons ; Humans ; Magnetic Resonance Imaging ; Multiparameter MRI mapping ; Myelination ; Schizophrenia ; Schizophrenia - genetics ; Schizotypal Personality Disorder - genetics</subject><ispartof>Biological psychiatry (1969), 2020-08, Vol.88 (3), p.248-259</ispartof><rights>2019</rights><rights>Crown Copyright © 2019. Published by Elsevier Inc. All rights reserved.</rights><rights>Crown Copyright © 2019 Published by Elsevier Inc on behalf of Society of Biological Psychiatry. 2019</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c471t-bf2526be9cc358ddeb54a8c11c61fb216129153d4eb67ea4d0ca6da2ab13afa93</citedby><cites>FETCH-LOGICAL-c471t-bf2526be9cc358ddeb54a8c11c61fb216129153d4eb67ea4d0ca6da2ab13afa93</cites><orcidid>0000-0002-1261-5884 ; 0000-0001-9183-0373 ; 0000-0002-0387-880X ; 0000-0002-5199-4573 ; 0000-0002-8164-7476 ; 0000-0002-5098-1527 ; 0000-0001-8498-4059</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0006322319319225$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>230,314,776,780,881,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32029217$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Romero-Garcia, Rafael</creatorcontrib><creatorcontrib>Seidlitz, Jakob</creatorcontrib><creatorcontrib>Whitaker, Kirstie J.</creatorcontrib><creatorcontrib>Morgan, Sarah E.</creatorcontrib><creatorcontrib>Fonagy, Peter</creatorcontrib><creatorcontrib>Dolan, Raymond J.</creatorcontrib><creatorcontrib>Jones, Peter B.</creatorcontrib><creatorcontrib>Goodyer, Ian M.</creatorcontrib><creatorcontrib>Suckling, John</creatorcontrib><creatorcontrib>Bullmore, Edward</creatorcontrib><creatorcontrib>Dolan, Raymond</creatorcontrib><creatorcontrib>Goodyer, Ian</creatorcontrib><creatorcontrib>Fonagy, Peter</creatorcontrib><creatorcontrib>Jones, Peter</creatorcontrib><creatorcontrib>Vaghi, Matilde</creatorcontrib><creatorcontrib>Moutoussis, Michael</creatorcontrib><creatorcontrib>Hauser, Tobias</creatorcontrib><creatorcontrib>Neufeld, Sharon</creatorcontrib><creatorcontrib>Romero-Garcia, Rafael</creatorcontrib><creatorcontrib>St Clair, Michelle</creatorcontrib><creatorcontrib>Whitaker, Kirstie</creatorcontrib><creatorcontrib>Inkster, Becky</creatorcontrib><creatorcontrib>Prabhu, Gita</creatorcontrib><creatorcontrib>Ooi, Cinly</creatorcontrib><creatorcontrib>Toseeb, Umar</creatorcontrib><creatorcontrib>Widmer, Barry</creatorcontrib><creatorcontrib>Bhatti, Junaid</creatorcontrib><creatorcontrib>Villis, Laura</creatorcontrib><creatorcontrib>Alrumaithi, Ayesha</creatorcontrib><creatorcontrib>Birt, Sarah</creatorcontrib><creatorcontrib>Bowler, Aislinn</creatorcontrib><creatorcontrib>Cleridou, Kalia</creatorcontrib><creatorcontrib>Dadabhoy, Hina</creatorcontrib><creatorcontrib>Davies, Emma</creatorcontrib><creatorcontrib>Firkins, Ashlyn</creatorcontrib><creatorcontrib>Granville, Sian</creatorcontrib><creatorcontrib>Harding, Elizabeth</creatorcontrib><creatorcontrib>Hopkins, Alexandra</creatorcontrib><creatorcontrib>Isaacs, Daniel</creatorcontrib><creatorcontrib>King, Janchai</creatorcontrib><creatorcontrib>Kokorikou, Danae</creatorcontrib><creatorcontrib>Maurice, Christina</creatorcontrib><creatorcontrib>McIntosh, Cleo</creatorcontrib><creatorcontrib>Memarzia, Jessica</creatorcontrib><creatorcontrib>Mills, Harriet</creatorcontrib><creatorcontrib>O’Donnell, Ciara</creatorcontrib><creatorcontrib>Pantaleone, Sara</creatorcontrib><creatorcontrib>Scott, Jenny</creatorcontrib><creatorcontrib>Fearon, Pasco</creatorcontrib><creatorcontrib>Suckling, John</creatorcontrib><creatorcontrib>Harmelen, Anne-Laura van</creatorcontrib><creatorcontrib>Kievit, Rogier</creatorcontrib><creatorcontrib>Vértes, Petra</creatorcontrib><creatorcontrib>Vértes, Petra E.</creatorcontrib><creatorcontrib>Bullmore, Edward T.</creatorcontrib><creatorcontrib>NSPN Consortium</creatorcontrib><title>Schizotypy-Related Magnetization of Cortex in Healthy Adolescence Is Colocated With Expression of Schizophrenia-Related Genes</title><title>Biological psychiatry (1969)</title><addtitle>Biol Psychiatry</addtitle><description>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.
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.
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.
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.</description><subject>Adolescence</subject><subject>Adolescent</subject><subject>Adult</subject><subject>Allen Human Brain Atlas</subject><subject>Brain - diagnostic imaging</subject><subject>Brain Mapping</subject><subject>Development</subject><subject>Fast-spiking GABAergic interneurons</subject><subject>Humans</subject><subject>Magnetic Resonance Imaging</subject><subject>Multiparameter MRI mapping</subject><subject>Myelination</subject><subject>Schizophrenia</subject><subject>Schizophrenia - genetics</subject><subject>Schizotypal Personality Disorder - 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Harriet</creatorcontrib><creatorcontrib>O’Donnell, Ciara</creatorcontrib><creatorcontrib>Pantaleone, Sara</creatorcontrib><creatorcontrib>Scott, Jenny</creatorcontrib><creatorcontrib>Fearon, Pasco</creatorcontrib><creatorcontrib>Suckling, John</creatorcontrib><creatorcontrib>Harmelen, Anne-Laura van</creatorcontrib><creatorcontrib>Kievit, Rogier</creatorcontrib><creatorcontrib>Vértes, Petra</creatorcontrib><creatorcontrib>Vértes, Petra E.</creatorcontrib><creatorcontrib>Bullmore, Edward T.</creatorcontrib><creatorcontrib>NSPN Consortium</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Biological psychiatry (1969)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Romero-Garcia, Rafael</au><au>Seidlitz, Jakob</au><au>Whitaker, Kirstie J.</au><au>Morgan, Sarah E.</au><au>Fonagy, Peter</au><au>Dolan, Raymond J.</au><au>Jones, Peter B.</au><au>Goodyer, Ian M.</au><au>Suckling, John</au><au>Bullmore, Edward</au><au>Dolan, Raymond</au><au>Goodyer, Ian</au><au>Fonagy, Peter</au><au>Jones, Peter</au><au>Vaghi, Matilde</au><au>Moutoussis, Michael</au><au>Hauser, Tobias</au><au>Neufeld, Sharon</au><au>Romero-Garcia, Rafael</au><au>St Clair, Michelle</au><au>Whitaker, Kirstie</au><au>Inkster, Becky</au><au>Prabhu, Gita</au><au>Ooi, Cinly</au><au>Toseeb, Umar</au><au>Widmer, Barry</au><au>Bhatti, Junaid</au><au>Villis, Laura</au><au>Alrumaithi, Ayesha</au><au>Birt, Sarah</au><au>Bowler, Aislinn</au><au>Cleridou, Kalia</au><au>Dadabhoy, Hina</au><au>Davies, Emma</au><au>Firkins, Ashlyn</au><au>Granville, Sian</au><au>Harding, Elizabeth</au><au>Hopkins, Alexandra</au><au>Isaacs, Daniel</au><au>King, Janchai</au><au>Kokorikou, Danae</au><au>Maurice, Christina</au><au>McIntosh, Cleo</au><au>Memarzia, Jessica</au><au>Mills, Harriet</au><au>O’Donnell, Ciara</au><au>Pantaleone, Sara</au><au>Scott, Jenny</au><au>Fearon, Pasco</au><au>Suckling, John</au><au>Harmelen, Anne-Laura van</au><au>Kievit, Rogier</au><au>Vértes, Petra</au><au>Vértes, Petra E.</au><au>Bullmore, Edward T.</au><aucorp>NSPN Consortium</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Schizotypy-Related Magnetization of Cortex in Healthy Adolescence Is Colocated With Expression of Schizophrenia-Related Genes</atitle><jtitle>Biological psychiatry (1969)</jtitle><addtitle>Biol Psychiatry</addtitle><date>2020-08-01</date><risdate>2020</risdate><volume>88</volume><issue>3</issue><spage>248</spage><epage>259</epage><pages>248-259</pages><issn>0006-3223</issn><issn>1873-2402</issn><eissn>1873-2402</eissn><abstract>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.
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.
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.
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.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>32029217</pmid><doi>10.1016/j.biopsych.2019.12.005</doi><tpages>12</tpages><orcidid>https://orcid.org/0000-0002-1261-5884</orcidid><orcidid>https://orcid.org/0000-0001-9183-0373</orcidid><orcidid>https://orcid.org/0000-0002-0387-880X</orcidid><orcidid>https://orcid.org/0000-0002-5199-4573</orcidid><orcidid>https://orcid.org/0000-0002-8164-7476</orcidid><orcidid>https://orcid.org/0000-0002-5098-1527</orcidid><orcidid>https://orcid.org/0000-0001-8498-4059</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0006-3223 |
| ispartof | Biological psychiatry (1969), 2020-08, Vol.88 (3), p.248-259 |
| issn | 0006-3223 1873-2402 1873-2402 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7369635 |
| source | MEDLINE; Elsevier ScienceDirect Journals |
| subjects | Adolescence Adolescent Adult Allen Human Brain Atlas Brain - diagnostic imaging Brain Mapping Development Fast-spiking GABAergic interneurons Humans Magnetic Resonance Imaging Multiparameter MRI mapping Myelination Schizophrenia Schizophrenia - genetics Schizotypal Personality Disorder - genetics |
| title | Schizotypy-Related Magnetization of Cortex in Healthy Adolescence Is Colocated With Expression of Schizophrenia-Related Genes |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-08T12%3A49%3A42IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Schizotypy-Related%20Magnetization%20of%20Cortex%20in%20Healthy%20Adolescence%20Is%20Colocated%20With%20Expression%20of%20Schizophrenia-Related%20Genes&rft.jtitle=Biological%20psychiatry%20(1969)&rft.au=Romero-Garcia,%20Rafael&rft.aucorp=NSPN%20Consortium&rft.date=2020-08-01&rft.volume=88&rft.issue=3&rft.spage=248&rft.epage=259&rft.pages=248-259&rft.issn=0006-3223&rft.eissn=1873-2402&rft_id=info:doi/10.1016/j.biopsych.2019.12.005&rft_dat=%3Cproquest_pubme%3E2352635031%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2352635031&rft_id=info:pmid/32029217&rft_els_id=S0006322319319225&rfr_iscdi=true |