Association of serotonin and dopamine gene pathways with behavioral subphenotypes in dementia

Proitsi, Petroula, Lupton, Michelle K., Reeves, Suzanne J., Hamilton, Gillian, Archer, Nicola, Martin, Belinda M., Iyegbe, Conrad, Hollingworth, Paul, Lawlor, Brian, Gill, Michael, Brayne, Carol, Rubinsztein, David C., Owen, Michael John ORCID: https://orcid.org/0000-0003-4798-0862, Williams, Julie ORCID: https://orcid.org/0000-0002-4069-0259, Lovestone, Simon and Powell, John F. 2012. Association of serotonin and dopamine gene pathways with behavioral subphenotypes in dementia. Neurobiology of Aging 33 (4) , pp. 791-803. 10.1016/j.neurobiolaging.2010.06.011

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Abstract

Genetic 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 behavioralsubphenotypes “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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine Systems Immunity Research Institute (SIURI) MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG) Neuroscience and Mental Health Research Institute (NMHRI)
Subjects:	R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry R Medicine > RM Therapeutics. Pharmacology
Uncontrolled Keywords:	Alzheimer's disease (AD); BPSD; Multiple indicators multiple causes (MIMIC) model; Genes; Dopamine; Serotonin; Medication; Interactions; Covariates; SNP; NPI
Publisher:	Elsevier
ISSN:	0197-4580
Last Modified:	19 Oct 2022 10:50
URI:	https://orca.cardiff.ac.uk/id/eprint/25721

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