Dopamine receptor gene (DRD2)‎ polymorphism and psychopathology in late onset alzheimer’s disease

Abstract EN

Background : Introduction: The clinical spectrum of Alzheimer’s disease (AD) is varied and includes both behavioural and psychological symptoms (BPS) that contribute to the difficulties experienced by families and carers.

The mechanism whereby these symptoms occur in some individuals with AD is not understood.

We hypothesised that common genetic polymorphisms in neurotransmitter systems, particularly genes that showed some association with psychiatric diseases and related disorders and that their products are known to be involved in these disorders’ pathophysiology e.g.

DRD2 gene, are risk factors for BPSD in the course of AD.

Two of the DRD2 polymorphisms (S311C,-141C Ins / Del) were previously reported to be associated with schizophrenia in several individual studies, however, only the former was investigated for possible association with psychosis and aggression in individuals with AD and BPSD.

Methods : Investigation of 432 clinically relevant individuals with AD were assessed for presence or absence of BPSD using the Neuropsychiatric Inventory (NPI).

This sample was genotyped for the DRD2 –141C Ins / Del polymorphism.

Results : A significant association between the C insertion and appetite disturbance (OR 0.62, CI 0.40-0.96, Chi sq = 4.65, P = 0.03) was found.

No statistically significant association between the–141C Del allele and other BPSD symptoms was revealed.

However, an increase of homozygotes for the deletion allele with the presence of delusions, depression, apathy, aberrant motor behaviour, sleep disturbance and anxiety was detected.

Having said that, the frequency of homozygotes in this population was very low.

This is the first study of DRD2 –141C Ins / Del polymorphism in BPSD and generates the hypothesis that it may play a role in appetite control.

This requires further examination in independent cohorts.