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


CONCLUSIONS
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.
Pritchard
Antonia L
AL
Molecular Psychiatry Group, Population Studies and Human Genetics, G Floor CBCRC Building, Queensland Institute of Medical Research, Herston, Brisbane, 4006, Australia. Antonia.Pritchard@qimr.edu.au
Ratcliffe
Laura
L
Sorour
Eman
E
Haque
Sayeed
S
Holder
Roger
R
Bentham
Peter
P
Lendon
Corinne L
CL
D000368:Aged; D000544:Alzheimer Disease / Q000235:genetics* / Q000523:psychology; D050483:Dopamine Plasma Membrane Transport Proteins / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D001523:Mental Disorders / Q000235:genetics / Q000523:psychology; D011954:Receptors, Dopamine / Q000235:genetics*; D012307:Risk Factors
D050483:Dopamine Plasma Membrane Transport Proteins; D011954:Receptors, Dopamine