Psychosis and aggression in Alzheimer's disease: the effect of dopamine receptor gene variation

Abstract

This study investigated possible associations between selected polymorphisms in the dopamine receptor genes DRD1 and DRD3 with the presence of psychotic phenomena or aggressive behaviour in a community based cohort of 134 patients with late onset Alzheimer's disease. An association was found between the presence of psychotic symptoms and aggressive behaviour and the DRD1 polymorphism and between the presence of psychosis, but not aggression, and the DRD3 polymorphism. Specifically, carriers of the DRD1 B2 allele were more likely to be aggressive or experience hallucinations whereas homozygous carriers of the DRD3 1 allele were more likely to experience delusions. (J Neurol Neurosurg Psychiatry 2001;71:777-779) Keywords: Alzheimer's disease; genetics; behaviour Cognitive decline is, by definition, invariably present in Alzheimer's disease. However, various other behavioural and psychological symptoms in dementia (BPSD) are also present, with psychotic symptoms found in about a third of cases and aggressive behaviour in around a half. The mechanism by which BPSD occurs in some patients with Alzheimer's disease is not completely understood but we have previously shown that common genetic polymorphisms in the serotonin receptors 5-HT2A and 5-HT2C are associated with the presence of psychotic phenomena, particularly hallucinations, in Alzheimer's disease.1 More recently, a study of the dopamine DRD1, 2, 3, and 4 receptors 2 has suggested an association between common polymorphisms in the DRD1 and DRD3 receptors and the presence of aggression and psychosis in Alzheimer's disease. This study was designed to examine the role that these polymorphisms might have on the development of specific components of psychotic phenomena-namely, the presence of delusions and hallucinations in patients with late onset Alzheimer's disease. Methods PATIENTSPatients were selected from the Camberwell Dementia Case Register. This is a community based register consisting of patients referred to psychiatric, medical, and social services with the districts of East Lambeth and South Southwark (formerly Camberwell), London, from April 1993 to April 1995. All patients were screened using the minimental state examination (MMSE) and any patients scoring less than 24 points were included for further assessment. Of the 528 patients fulfilling these criteria 374 also fulfilled the The patients and the next of kin or main carer were interviewed in all cases by means of the CAMDEX 5 and the presence of a psychiatric history defined according to these guidelines-that is, an emotional or nervous illness requiring treatment. Presence of psychopathology was assessed by the Manchester and Oxford Universities scale for the psychological assessment of dementia (MOUSE-PAD).6 Due to possible ethnic diVerences in the frequencies of DRD1 and DRD3 receptor polymorphisms only white persons were included in this study. SuYcient genetic material was available for DRD3 genotyping in 129 cases and for DRD1 genotyping in 105 cases.Ethical approval was obtain...

Syndromes of behavioural and psychological symptoms in mild Alzheimer's disease

“…Previously, certain behavioural and psychological symptoms have been shown to aggregate in affected siblings with AD (Tunstall et al, 2000). An association has been reported between the presence of psychotic symptoms and aggressive behaviour and the DRD1 polymorphism in the dopamine receptor genes, and the presence of psychotic symptoms but not aggression and the DRD3 polymorphism (Holmes et al, 2001).…”

Neurobiology of Delusions in Alzheimer’s Disease

“…Homozygosity for the long arm leads to an increase in 5HTT mRNA transcription and 5HT uptake compared with genes containing at least one short arm and is protective for AD+D [46]. The dopaminergic system also has been investigated, with dopamine receptor DRD3 1/1 allele implicated in delusions compared with the DRD3 2/2 allele [47]. However, much more work is required to help us better understand the role of neurotransmitter genetics in AD+D.…”

Catechol-O-Methyltransferase GeneticVariant Associated with the Risk of Alzheimer’s Disease in a Brazilian Population

“…COMT encodes for a protein which catalyzes the degradation of catecholamine, thus inactivating dopamine [22,24,38,39]. Dopaminergic pathways play an important role in the pathogenesis of dementia [13].…”