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dc.contributor.authorGill, Michaelen
dc.contributor.authorLawlor, Brianen
dc.date.accessioned2011-03-16T15:32:44Z
dc.date.available2011-03-16T15:32:44Z
dc.date.issued2012en
dc.date.submitted2012en
dc.identifier.citationProitsi P, Lupton MK, Reeves SJ, Hamilton G, Archer N, Martin BM, Lyegbe C, Hollingworth P, Lawlor B, Gill M, Brayne C, Rubinsztein DC, Owen MJ, Williams J, Lovestone S, Powell JF., Association of serotonin and dopamine gene pathways with behavioural subphenotypes in dementia., Neurobiology of Aging, 33, 4, 2012, 791-803en
dc.identifier.otherYen
dc.identifier.urihttp://hdl.handle.net/2262/53323
dc.descriptionPUBLISHEDen
dc.descriptionpmid:20685009en
dc.description.abstractGenetic association studies investigating the association between genes of serotonergic and dopaminergic systems and behavioral and psychological symptoms in dementia (BPSD) are contradictory. We have utilized 1008 probable Alzheimer's disease (AD) patients from the UK and used the 12-item Neuropsychiatric Inventory. We applied a multiple indicators-multiple causes (MIMIC) approach to investigate the effect of 11 polymorphisms on the 4 behavioral subphenotypes "psychosis", "moods", "agitation", and "behavioural dyscontrol". Significant associations were observed between the serotonin transporter gene (SERT) polymorphism STin2 and "psychosis"; the dopamine transporter gene (DAT) 3' variable number tandem repeats (VNTR) and "agitation"; and the dopamine receptor 4 (DRD4) VNTR and "moods" factors. Direct associations were identified between the dopamine receptor 3 (DRD3) BalI polymorphism and depression; the dopamine receptor 1 (DRD1) and dopamine transporter gene 3' VNTR polymorphisms and aberrant motor behavior; the DRD4 VNTR and sleep disturbances; and the SERT gene VNTR 5HTTLPR and apathy items. Significant interactions observed between polymorphisms suggested epistatic effects and interactions between polymorphisms and medications highlighted potential treatment response. This multiple indicators multiple causes (MIMIC) model efficiently captured the complexity of the interrelations between genetic variation, behavioral symptoms, and clinical variables.en
dc.description.sponsorshipWe are grateful for funding from the Alzheimer's Research Trust, the MRC Centre for Neurodegeneration Research, the NIHR BRC Centre for Mental Health at the South London and Maudsley NHS Foundation Trust and Institute of Psychiatry, KCL, and the Alzheimer's Society.en
dc.format.extent791-803en
dc.language.isoenen
dc.relation.ispartofseriesNeurobiology of Agingen
dc.relation.ispartofseries33en
dc.relation.ispartofseries4en
dc.rightsYen
dc.subjectNeuroscienceen
dc.subjectAlzheimer's diseaseen
dc.titleAssociation of serotonin and dopamine gene pathways with behavioural subphenotypes in dementia.en
dc.typeJournal Articleen
dc.type.supercollectionscholarly_publicationsen
dc.type.supercollectionrefereed_publicationsen
dc.identifier.peoplefinderurlhttp://people.tcd.ie/mgillen
dc.identifier.peoplefinderurlhttp://people.tcd.ie/lawlorbaen
dc.identifier.rssinternalid67996en
dc.subject.TCDThemeGenes & Societyen
dc.identifier.rssurihttp://dx.doi.org/10.1016/j.neurobiolaging.2010.06.011en
dc.identifier.orcid_id0000-0003-0206-5337en


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