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Genes of the serotonergic and dopaminergic pathways and their interaction affect the expression of Behavioural and Psychological Symptoms in Dementia (BPSD).

Petroula Proitsi¹, Michelle Lupton¹, Suzanne Reeves², Gillian Hamilton³, Nicola Archer², Belinda Martin², Paul hollingworth⁴, Brian Lawlord⁵, Michael Gill⁵, Michael J. Owen⁴, Julie Williams⁴, Simon Lovestone² & John Powell¹

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1. King's College London, Institute of Psychiatry, Neuroscience
2. King's College London, Institute of Psychiatry, Old Age Psychiatry
3. Molecular Medicine Centre, Medical Genetics, Western General Hospital, University of Edinburgh
4. University of Wales College of Medicine, Department of Psychological Medicine
5. Mercer’s Institute for Research on Aging, St. James’s Hospital and Trinity College

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Date:

Received 23 October 2009 20:37 UTC; Posted 26 October 2009

Subjects:

Genetics & Genomics, Neuroscience

Tags:

• Alzheimer's disease
• BPSD
• Multiple Indicators Multiple Causes (MIMIC) model
• genes
• interactions
• associations
• serotonin
• dopamine

Abstract:

Although there is evidence for the involvement of genes of serotonergic and dopaminergic systems in the manifestation of the Behavioural and Psychological Symptoms in Dementia (BPSD), genetic association studies are contradictory. We used 1008 probable AD patients from the UK and applied a Multiple Indicators Multiple Causes (MIMIC) approach to investigate the effect of 11 polymorphisms in the serotonergic and dopaminergic systems, on four behavioural sub-phenotypes, namely "psychosis"," moods", "agitation" and "behavioural dyscontrol", as well as on 12 NPI items. Significant findings included the association of DRD1 A48G with "psychosis" (p=0.037), the association of DAT1 VNTR with "agitation" (p=0.006) and the association of DRD4 with "moods" sub-phenotype (p=0.008). In addition, associations were identified between DRD1 A48G and DAT1 VNTR with aberrant motor behaviour (AMB) symptoms (p=0.001 and p=0.015 respectively), between DRD4 and sleep disturbances (p=0.018) and between 5HTTLPR and apathy (p=0.033). Finally, significant interactions were observed between COMT Val158Met and 5HTTLPR with "psychosis" (p=0.026), between HTTLPR and STin2 with "psychosis" (p=0.005), between DAT1 3'UTR VNTR and COMT Val158Met with "agitation" (p=0.0001) and between DAT1 3'UTR VNTR and 5HTTLPR with the "moods" factor (p=0.0027). The complexity of the interrelations between genetic variation, behavioural symptoms and clinical variables was efficiently captured by this MIMIC model.

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This document is licensed to the public under the Creative Commons Attribution 3.0 License

How to cite this document:

Proitsi, Petroula, Lupton, Michelle, Reeves, Suzanne, Hamilton, Gillian, Archer, Nicola, Martin, Belinda, hollingworth, Paul, Lawlord, Brian, Gill, Michael, Owen, Michael, Williams, Julie, Lovestone, Simon, and Powell, John. Genes of the serotonergic and dopaminergic pathways and their interaction affect the expression of Behavioural and Psychological Symptoms in Dementia (BPSD).. Available from Nature Precedings <http://hdl.handle.net/10101/npre.2009.3896.1> (2009)

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