Investigation of dopamine receptors in susceptibility to behavioural and psychological symptoms in Alzheimer's disease

Antonia L. Pritchard, Laura Ratcliffe, Eman Sorour, Sayeed Haque, Roger Holder, Peter Bentham, Corinne L. Lendon

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Objective
Alzheimer's disease (AD) patients commonly suffer from behavioural and psychological symptoms of dementia (BPSD). A genetic component to the development of BPSD in AD has been supported. Polymorphisms within dopamine receptors DRD1, DRD2, DRD3 and DRD4 have previously been investigated in a few interesting studies that are reviewed here and extended using our patient cohort.
Methods
Our large cohort of 395 probable AD patients had longitudinal information on the BPSD (Neuropsychiatric Inventory), which was used to dichotomise patients into whether they had ever suffered from a given symptom within the study period, or not. These measures were related to the DRD1 (A-48G), DRD2 (ser311cys; C-ins/del), DRD3 (ser9gly) and DRD4 (VNTR) genotype and allele frequencies.
Results
Associations were revealed between DRD3 and elation, and between DRD4 with agitation/aggression and with depression; however, these findings do not remain significant after correction for multiple testing. No associations were found with the other genetic variants and these symptoms and no associations were observed between any of the polymorphic variants examined and delusions, hallucinations, psychosis and aberrant motor behaviour.
Conclusion
Our data, in combination with a review of the literature, reveal a potential role for the VNTR variant of DRD4 in the development of depression in AD patients. The findings presented here need to be replicated in large, well characterised longitudinal cohorts.
Original languageEnglish
Pages (from-to)1020-1025
Number of pages6
JournalInternational Journal of Geriatric Psychiatry
Volume24
Issue number9
DOIs
Publication statusPublished - Sep 2009

Keywords

  • Alzheimer's
  • psychosis
  • depression
  • aggression
  • dopamine
  • elation/mania

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