Role of serotonin transporter polymorphisms in the behavioural and psychological symptoms in probable Alzheimer Disease patients

Background/ Aims: Alzheimer disease ( AD) patients commonly suffer from behavioural and psychological symptoms of dementia (BPSD). A genetic component to BPSD development in AD has been demonstrated. This is an investigation of whether the linked polymorphic region and variable number tandem repeat variants of the serotonin transporter (SERT) are associated with BPSD. Methods: The longitudinal measures of BPSD of our large cohort of 367 AD patients were assessed by the Neuropsychiatric Inventory. Measures with good evidence of serotonergic involvement ( delusions, hallucinations, depression, anxiety, agitation/aggression and irritability) were related to genotype and allele frequencies of the linked polymorphic region and variable number tandem repeat variants. Results: Analysis revealed significant relationships between the linked polymorphic region variant long allele with irritability and the variable number tandem repeat 10-repeat allele with psychosis, but no associations were found with depression, anxiety or agitation/aggression. Conclusion: Our data and review of previous studies suggest SERT could play a minor role in development of psychosis and aggressive/irritable tendencies; however, further investigations are required in large, well-characterized cohorts

Investigation of the role of the dopamine transporter in susceptibility to behavioural and psychological symptoms of patients with probable Alzheimer's Disease

Background/Aims: 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. Conclusion: 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. Copyright (C) 2008 S. Karger AG, Base

A polymorphism in the presenilin 1 gene does not modify risk for Alzheimer's disease in a cohort with sporadic early onset

Mutations in the presenilin 1 gene account for many cases of early onset familial Alzheimer's disease. Homozygosity for the `T' allele of a polymorphism in the presenilin 1 gene has previously been reported to double the risk for Alzheimer's disease in a late onset Caucasian sample. Here we report that this polymorphism does not incur risk in a case control sample of early onset Alzheimer's disease, possibly suggesting a different disease etiology between the early and late onset forms

No association between neuregulin 1 and psychotic symptoms in Alzheimer's disease patients

Alzheimer's disease (AD) patients commonly suffer from behavioral and psychological symptoms of dementia (BPSD). Variants within the neuregulin-1 (NRG1) gene have been investigated both in early onset psychiatric disorders, such as schizophrenia and recently in AD patients with psychosis. In this study, we analyzed NRG1 variants in AD patients with and without psychosis. Our large cohort of 399 probable AD patients had longitudinal information on the BPSD, which was used to dichotomize patients into whether they had ever suffered from psychotic symptoms within the study period. The NRG1 single nucleotide polymorphisms rs3924999, rs35753505 (SNP8NRG221533) and the microsatellites 478B14-848 and 420M9-1395 were investigated for association with psychosis using genotype, allele, and haplotype analyses. No associations were found between any of these variants or haplotypic combinations with delusions, hallucinations, psychosis, or elation/mania in our cohort. Positive associations with polymorphisms and haplotype combinations of NRG1 have been reported in psychiatric disorders. One previous study found an association with psychosis in AD, with a SNP outside the haplotype block first reported for association with schizophrenia. We found no association with any of these variants in our cohort. Further investigations of this region on chromosome 8 are clearly required, with replication in different large longitudinal cohorts. © 2010 - IOS Press and the authors. All rights reserved

Role of 5HT2A and 5HT2C polymorphisms in behavioural and psychological symptoms of Alzheimer's disease

Objective: Alzheimer's disease (AD) patients suffer from behavioural and psychological symptoms of dementia (BPSD). A genetic component to BPSD development in AD has been demonstrated. Polymorphisms within serotonin receptors 5HT(2A) and 5HT(2C) have been previously investigated in a few interesting studies reviewed here, however, their role remains unclear