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

Pritchard, Antonia L.; Harris, Judith; Pritchard, Colin W.; Coates, John; Haque, Sayeed; Holder, Roger; Bentham, Peter; Lendon, Corinne L.

doi:10.1016/j.neurobiolaging.2006.10.011

« Previous Next »Neurobiology of Aging
Volume 29, Issue 3 , Pages 341-347, March 2008

Role of 5HT_2A and 5HT_2C polymorphisms in behavioural and psychological symptoms of Alzheimer's disease

Antonia L. Pritchard
- Department of Human Genetics, G Floor CBCRC Building, Queensland Institute of Medical Research, 300 Herston Road, Herston, Brisbane 4006, Australia
- Corresponding author. Fax: +61 7 33620323.
Judith Harris
- Molecular Psychiatry Group, Institute of Biomedical Research, University of Birmingham, Vincent Drive B15 2TT, UK
Colin W. Pritchard
- R&D Support Unit, Treliske Hospital, Truro, Cornwall TR1 3HD, UK
John Coates
- Molecular Psychiatry Group, Institute of Biomedical Research, University of Birmingham, Vincent Drive B15 2TT, UK
Sayeed Haque
- Department of Psychiatry, Queen Elizabeth Psychiatric Hospital, University of Birmingham, Mindelson Way B15 2QZ, UK
Roger Holder
- Department of Psychiatry, Queen Elizabeth Psychiatric Hospital, University of Birmingham, Mindelson Way B15 2QZ, UK
Peter Bentham
- Department of Psychiatry, Queen Elizabeth Psychiatric Hospital, University of Birmingham, Mindelson Way B15 2QZ, UK
Corinne L. Lendon
- Department of Human Genetics, G Floor CBCRC Building, Queensland Institute of Medical Research, 300 Herston Road, Herston, Brisbane 4006, Australia
- Molecular Psychiatry Group, Institute of Biomedical Research, University of Birmingham, Vincent Drive B15 2TT, UK

Received 17 March 2006; received in revised form 28 September 2006; accepted 10 October 2006. published online 15 November 2006.

Abstract

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.

Methods

Our large cohort of 394 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 and give each patient a severity score. These measures were related to the 5HT_2A T102C and 5HT_2C cys23ser genotype and allele frequencies.

Results

Our data supports previous reports of an increased frequency of the C allele and CC genotype of the T102C variant of 5HT_2A with hallucinations, delusions, psychosis and aberrant motor behaviour, however, we dispute previous associations with depression and aggression. We describe for the first time an increase in the C allele and CC genotype frequencies of the cys23ser variant of 5HT_2C with anxiety and support previous associations with appetite disturbances in females.

Conclusion

This review and extension of previous data presents support for the role of 5HT_2A and 5HT_2C in the development of certain symptoms, although the effect size may be small.

Keywords: Alzheimer's, Psychosis, Appetite, Aberrant motor behaviour