Investigation of the role of the dopamine transporter in susceptibility to behavioural and psychological symptoms of patients with probable Alzheimer's disease.
OBJECTIVE
Alzheimer's disease patients commonly suffer from behavioural and psychological symptoms of dementia (BPSD); a genetic component to the development of BPSD has been demonstrated. Genetic risk factors for other psychiatric disorders have been implicated in BPSD; however, this is the first known investigation of the dopamine transporter (DAT1) gene in BPSD.


METHODS
Our large cohort of 395 patients with probable Alzheimer's disease was dichotomised into whether they had ever suffered from a given symptom over the study period or not, based on longitudinal data using the BPSD (Neuropsychiatric Inventory). These measures were related to the DAT1 3'-untranslated region (UTR) variable number tandem repeat (VNTR) polymorphism.


RESULTS
Potential associations were revealed between the 9-repeat allele and presence of irritability and between the 10-repeat allele and aberrant motor behaviour (AMB); however, these do not remain significant after correction for multiple testing. No associations were observed with delusions, hallucinations, depression, agitation/aggression or elation.


CONCLUSIONS
Our data suggest that the DAT1 3'-UTR VNTR could play a role in susceptibility to irritability and AMB. The findings presented here require replication in large well-characterised cohorts.
Pritchard
Antonia L
AL
Molecular Psychiatry Group, Population Studies and Human Genetics, Queensland Institute of Medical Research, Brisbane, Qld., Australia. Antonia.Pritchard@qimr.edu.au
Pritchard
Colin W
CW
Bentham
Peter
P
Lendon
Corinne L
CL
D020413:3' Untranslated Regions / Q000235:genetics; D000368:Aged; D000369:Aged, 80 and over; D000374:Aggression / Q000502:physiology; D000544:Alzheimer Disease / Q000453:epidemiology / Q000235:genetics* / Q000523:psychology*; D015331:Cohort Studies; D003863:Depression / Q000235:genetics; D050483:Dopamine Plasma Membrane Transport Proteins / Q000235:genetics* / Q000378:metabolism; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology; D005838:Genotype; D006801:Humans; D007508:Irritable Mood / Q000502:physiology; D008137:Longitudinal Studies; D008297:Male; D001523:Mental Disorders / Q000453:epidemiology / Q000235:genetics* / Q000523:psychology*; D010641:Phenotype; D012307:Risk Factors; D020080:Tandem Repeat Sequences
D020413:3' Untranslated Regions; D050483:Dopamine Plasma Membrane Transport Proteins