Effects of Schizophrenia Polygenic Risk Scores on Brain Activity and Performance During Working Memory Subprocesses in Healthy Young Adults
Abstract Recent work has begun to shed light on the neural correlates and possible mechanisms of polygenic risk for schizophrenia. Here, we map a schizophrenia polygenic risk profile score (PRS) based on genome-wide association study significant loci onto variability in the activity and functional c...
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| Veröffentlicht in: | Schizophrenia bulletin 2018-06, Vol.44 (4), p.844-853 |
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| container_title | Schizophrenia bulletin |
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| creator | Miller, Jacob A Scult, Matthew A Conley, Emily Drabant Chen, Qiang Weinberger, Daniel R Hariri, Ahmad R |
| description | Abstract
Recent work has begun to shed light on the neural correlates and possible mechanisms of polygenic risk for schizophrenia. Here, we map a schizophrenia polygenic risk profile score (PRS) based on genome-wide association study significant loci onto variability in the activity and functional connectivity of a frontoparietal network supporting the manipulation versus maintenance of information during a numerical working memory (WM) task in healthy young adults (n = 99, mean age = 19.8). Our analyses revealed that higher PRS was associated with hypoactivity of the dorsolateral prefrontal cortex (dlPFC) during the manipulation but not maintenance of information in WM (r2 = .0576, P = .018). Post hoc analyses revealed that PRS-modulated dlPFC hypoactivity correlated with faster reaction times during WM manipulation (r2 = .0967, P = .002), and faster processing speed (r2 = .0967, P = .003) on a separate behavioral task. These PRS-associated patterns recapitulate dlPFC hypoactivity observed in patients with schizophrenia during central executive manipulation of information in WM on this task. |
| doi_str_mv | 10.1093/schbul/sbx140 |
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Recent work has begun to shed light on the neural correlates and possible mechanisms of polygenic risk for schizophrenia. Here, we map a schizophrenia polygenic risk profile score (PRS) based on genome-wide association study significant loci onto variability in the activity and functional connectivity of a frontoparietal network supporting the manipulation versus maintenance of information during a numerical working memory (WM) task in healthy young adults (n = 99, mean age = 19.8). Our analyses revealed that higher PRS was associated with hypoactivity of the dorsolateral prefrontal cortex (dlPFC) during the manipulation but not maintenance of information in WM (r2 = .0576, P = .018). Post hoc analyses revealed that PRS-modulated dlPFC hypoactivity correlated with faster reaction times during WM manipulation (r2 = .0967, P = .002), and faster processing speed (r2 = .0967, P = .003) on a separate behavioral task. These PRS-associated patterns recapitulate dlPFC hypoactivity observed in patients with schizophrenia during central executive manipulation of information in WM on this task.</description><identifier>ISSN: 0586-7614</identifier><identifier>EISSN: 1745-1701</identifier><identifier>DOI: 10.1093/schbul/sbx140</identifier><identifier>PMID: 29040762</identifier><language>eng</language><publisher>US: Oxford University Press</publisher><subject>Adolescent ; Adult ; Female ; Genome-Wide Association Study ; Humans ; Magnetic Resonance Imaging ; Male ; Memory, Short-Term - physiology ; Multifactorial Inheritance ; Prefrontal Cortex - diagnostic imaging ; Prefrontal Cortex - physiology ; Regular ; Schizophrenia - genetics ; Young Adult</subject><ispartof>Schizophrenia bulletin, 2018-06, Vol.44 (4), p.844-853</ispartof><rights>The Author 2017. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com 2017</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c420t-33feaf6c6026170de57095694af61dc654703d0d7302d69455f345f2ab3897283</citedby><cites>FETCH-LOGICAL-c420t-33feaf6c6026170de57095694af61dc654703d0d7302d69455f345f2ab3897283</cites><orcidid>0000-0001-6599-7321</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6007653/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6007653/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,723,776,780,881,1578,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29040762$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Miller, Jacob A</creatorcontrib><creatorcontrib>Scult, Matthew A</creatorcontrib><creatorcontrib>Conley, Emily Drabant</creatorcontrib><creatorcontrib>Chen, Qiang</creatorcontrib><creatorcontrib>Weinberger, Daniel R</creatorcontrib><creatorcontrib>Hariri, Ahmad R</creatorcontrib><title>Effects of Schizophrenia Polygenic Risk Scores on Brain Activity and Performance During Working Memory Subprocesses in Healthy Young Adults</title><title>Schizophrenia bulletin</title><addtitle>Schizophr Bull</addtitle><description>Abstract
Recent work has begun to shed light on the neural correlates and possible mechanisms of polygenic risk for schizophrenia. Here, we map a schizophrenia polygenic risk profile score (PRS) based on genome-wide association study significant loci onto variability in the activity and functional connectivity of a frontoparietal network supporting the manipulation versus maintenance of information during a numerical working memory (WM) task in healthy young adults (n = 99, mean age = 19.8). Our analyses revealed that higher PRS was associated with hypoactivity of the dorsolateral prefrontal cortex (dlPFC) during the manipulation but not maintenance of information in WM (r2 = .0576, P = .018). Post hoc analyses revealed that PRS-modulated dlPFC hypoactivity correlated with faster reaction times during WM manipulation (r2 = .0967, P = .002), and faster processing speed (r2 = .0967, P = .003) on a separate behavioral task. These PRS-associated patterns recapitulate dlPFC hypoactivity observed in patients with schizophrenia during central executive manipulation of information in WM on this task.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Female</subject><subject>Genome-Wide Association Study</subject><subject>Humans</subject><subject>Magnetic Resonance Imaging</subject><subject>Male</subject><subject>Memory, Short-Term - physiology</subject><subject>Multifactorial Inheritance</subject><subject>Prefrontal Cortex - diagnostic imaging</subject><subject>Prefrontal Cortex - physiology</subject><subject>Regular</subject><subject>Schizophrenia - genetics</subject><subject>Young Adult</subject><issn>0586-7614</issn><issn>1745-1701</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkU1v1DAQhi0EokvhyBX5yCXU39lckJZSaKWiVhSEOFmOY29MEzu144rwF_jTdbWlhRPyYayZZ96x5wXgJUZvMGroQdJ9m4eD1P7EDD0CK1wzXuEa4cdghfhaVLXAbA88S-kHQpg1gjwFe6RBDNWCrMDvI2uNnhMMFl7o3v0KUx-Ndwqeh2HZlpuGn126LMUQTcE8fBeV83CjZ3ft5gUq38FzE22Io_LawPc5Or-F30K8vI2fzBjiAi9yO8WgTUpFpLQfGzXM_QK_h1ygTZeHOT0HT6waknlxF_fB1w9HXw6Pq9OzjyeHm9NKM4LmilJrlBVaICLKRzvDa9Rw0bCSxJ0WnNWIdqirKSJdSXNuKeOWqJaum5qs6T54u9OdcjuaThs_RzXIKbpRxUUG5eS_Fe96uQ3XUqCyNE6LwOs7gRiuskmzHF3SZhiUNyEniRtOyhFrUdBqh-oYUorG3o_BSN4aKHcGyp2BhX_199vu6T-OPcwOefqP1g3l_ql_</recordid><startdate>20180606</startdate><enddate>20180606</enddate><creator>Miller, Jacob A</creator><creator>Scult, Matthew A</creator><creator>Conley, Emily Drabant</creator><creator>Chen, Qiang</creator><creator>Weinberger, Daniel R</creator><creator>Hariri, Ahmad R</creator><general>Oxford University Press</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0001-6599-7321</orcidid></search><sort><creationdate>20180606</creationdate><title>Effects of Schizophrenia Polygenic Risk Scores on Brain Activity and Performance During Working Memory Subprocesses in Healthy Young Adults</title><author>Miller, Jacob A ; Scult, Matthew A ; Conley, Emily Drabant ; Chen, Qiang ; Weinberger, Daniel R ; Hariri, Ahmad R</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c420t-33feaf6c6026170de57095694af61dc654703d0d7302d69455f345f2ab3897283</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Female</topic><topic>Genome-Wide Association Study</topic><topic>Humans</topic><topic>Magnetic Resonance Imaging</topic><topic>Male</topic><topic>Memory, Short-Term - physiology</topic><topic>Multifactorial Inheritance</topic><topic>Prefrontal Cortex - diagnostic imaging</topic><topic>Prefrontal Cortex - physiology</topic><topic>Regular</topic><topic>Schizophrenia - genetics</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Miller, Jacob A</creatorcontrib><creatorcontrib>Scult, Matthew A</creatorcontrib><creatorcontrib>Conley, Emily Drabant</creatorcontrib><creatorcontrib>Chen, Qiang</creatorcontrib><creatorcontrib>Weinberger, Daniel R</creatorcontrib><creatorcontrib>Hariri, Ahmad R</creatorcontrib><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>Schizophrenia bulletin</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Miller, Jacob A</au><au>Scult, Matthew A</au><au>Conley, Emily Drabant</au><au>Chen, Qiang</au><au>Weinberger, Daniel R</au><au>Hariri, Ahmad R</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Effects of Schizophrenia Polygenic Risk Scores on Brain Activity and Performance During Working Memory Subprocesses in Healthy Young Adults</atitle><jtitle>Schizophrenia bulletin</jtitle><addtitle>Schizophr Bull</addtitle><date>2018-06-06</date><risdate>2018</risdate><volume>44</volume><issue>4</issue><spage>844</spage><epage>853</epage><pages>844-853</pages><issn>0586-7614</issn><eissn>1745-1701</eissn><abstract>Abstract
Recent work has begun to shed light on the neural correlates and possible mechanisms of polygenic risk for schizophrenia. Here, we map a schizophrenia polygenic risk profile score (PRS) based on genome-wide association study significant loci onto variability in the activity and functional connectivity of a frontoparietal network supporting the manipulation versus maintenance of information during a numerical working memory (WM) task in healthy young adults (n = 99, mean age = 19.8). Our analyses revealed that higher PRS was associated with hypoactivity of the dorsolateral prefrontal cortex (dlPFC) during the manipulation but not maintenance of information in WM (r2 = .0576, P = .018). Post hoc analyses revealed that PRS-modulated dlPFC hypoactivity correlated with faster reaction times during WM manipulation (r2 = .0967, P = .002), and faster processing speed (r2 = .0967, P = .003) on a separate behavioral task. These PRS-associated patterns recapitulate dlPFC hypoactivity observed in patients with schizophrenia during central executive manipulation of information in WM on this task.</abstract><cop>US</cop><pub>Oxford University Press</pub><pmid>29040762</pmid><doi>10.1093/schbul/sbx140</doi><tpages>10</tpages><orcidid>https://orcid.org/0000-0001-6599-7321</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Adolescent Adult Female Genome-Wide Association Study Humans Magnetic Resonance Imaging Male Memory, Short-Term - physiology Multifactorial Inheritance Prefrontal Cortex - diagnostic imaging Prefrontal Cortex - physiology Regular Schizophrenia - genetics Young Adult |
| title | Effects of Schizophrenia Polygenic Risk Scores on Brain Activity and Performance During Working Memory Subprocesses in Healthy Young Adults |
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