The impact of psychosis genome-wide associated ZNF804A variation on verbal fluency connectivity

buir.contributor.authorToulopoulou, Timothea
dc.citation.epage21en_US
dc.citation.spage17en_US
dc.citation.volumeNumber98en_US
dc.contributor.authorTecelão, D.en_US
dc.contributor.authorMendes, A.en_US
dc.contributor.authorMartins, D.en_US
dc.contributor.authorBramon, E.en_US
dc.contributor.authorToulopoulou, Timotheaen_US
dc.contributor.authorKravariti, E.en_US
dc.contributor.authorMurray, R.en_US
dc.contributor.authorPrata, D.en_US
dc.date.accessioned2019-02-21T16:01:47Z
dc.date.available2019-02-21T16:01:47Z
dc.date.issued2018en_US
dc.departmentDepartment of Psychologyen_US
dc.description.abstractSchizophrenia (SCZ) and bipolar disorder (BD) have high heritability. Genome-wide association studies (GWAS) have identified ZNF804A as a significant risk gene for both illnesses. A validation of this finding at the brain systems-level is imperative as there is still little understanding of how it heightens risk. Based in part on our recent findings of an effect on widespread decreased white matter microstructural fractional anisotropy (putatively a proxy of its integrity), particularly strong in SCZ, we asked whether the risk allele has a detrimental effect on regional brain activation and functional connectivity during a type of cognitive processing which is, together with its neural correlates, impaired in BD and SCZ: verbal fluency. Functional MRI and genotype data was collected from 80 healthy volunteers, and 54 SCZ and 40 BD patients. A standard multifactorial analysis of variance using statistical parametric mapping and significance correction of FWE p < 0.05 was used. We found the GWAS risk allele A was associated with decreased positive functional coupling between the left precentral gyrus/inferior frontal gyrus (i.e. the most highly recruited area for the task) and: 1) the left inferior frontal gyrus, and 2) the left posterior cingulate gyrus, encompassing the precuneus; both as a main effect across controls and psychosis patients. Such association of the risk allele with reduced functional connectivity (with no area where the opposite main effect was detected), converges with findings in other tasks, our previous finding of its widespread impact on brain white matter microstructure, and with the dysconnectivity hypothesis of SCZ.
dc.description.provenanceMade available in DSpace on 2019-02-21T16:01:47Z (GMT). No. of bitstreams: 1 Bilkent-research-paper.pdf: 222869 bytes, checksum: 842af2b9bd649e7f548593affdbafbb3 (MD5) Previous issue date: 2018en
dc.description.sponsorshipDP was supported by a UK National Institute for Health Research fellowship (NIHR, PDF-2010-03-047 ), a Marie Curie Career Integration grant ( FP7-PEOPLE-2013-CIG-631952 ) and a Fundação para Ciência e Tecnologia (FCT) Investigator grant ( IF/00787/2014 ) and is co-founder of neuroimaging services company NeuroPsyAI, Ltd. DM was supported by a Fundação Ciência e Tecnologia (FCT) PhD fellowship ( PD/BD/114098/2015 ) and the 13th joint award from AstraZeneca and the Faculdade de Medicina da Universidade de Lisboa . EB was supported by a Medical Research Council (MRC) New Investigator Award ( G0901310 ) and the Wellcome Trust ( 085475/B/08/Z and 085475/Z/08/Z ), a NIHR post-doctoral fellowship ( PDA/02/06/016 ), the Wellcome Trust ( 085475/B/08/Z and 085475/Z/08/Z ) and the British Medical Association's Margaret Temple Fellowship 2016. This study was supported by the NIHR Biomedical Research Centres at University College London and at King’s College London - South London and Maudsley NHS Foundation Trust . None of the authors declare any conflict of interest. Appendix A
dc.identifier.doi10.1016/j.jpsychires.2017.12.005
dc.identifier.eissn1879-1379en_US
dc.identifier.issn0022-3956
dc.identifier.urihttp://hdl.handle.net/11693/49918
dc.language.isoEnglish
dc.publisherElsevier
dc.relation.isversionofhttps://doi.org/10.1016/j.jpsychires.2017.12.005
dc.relation.projectG0901310 - FP7-PEOPLE-2013-CIG-631952, PDF-2010-03-047 - Wellcome Trust: 085475/Z/08/Z, 085475/B/08/Z - South London and Maudsley NHS Foundation Trust - Fuel Cell Technologies Program, FCT: IF/00787/2014 - AstraZeneca - National Institute for Health Research, NIHR: PDA/02/06/016 - Faculdade de Medicina da Universidade de São Paulo, FMUSP - Fundação para a Ciência e a Tecnologia, FCT: PD/BD/114098/2015 - Fundação para a Ciência e a Tecnologia, FCT
dc.rightsinfo:eu-repo/semantics/openAccess
dc.source.titleJournal of Psychiatric Researchen_US
dc.subjectBipolar disorderen_US
dc.subjectGenome-wide associationen_US
dc.subjectNeuroimaging geneticsen_US
dc.subjectPsychosisen_US
dc.subjectSchizophreniaen_US
dc.subjectZNF804Aen_US
dc.titleThe impact of psychosis genome-wide associated ZNF804A variation on verbal fluency connectivityen_US
dc.typeArticleen_US

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