Role of 5HT 2A and 5HT 2C 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.


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.


CONCLUSIONS
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.
Pritchard
Antonia L
AL
Department of Human Genetics, G Floor CBCRC Building, Queensland Institute of Medical Research, 300 Herston Road, Herston, Brisbane 4006, Australia. Antonia.Pritchard@qimr.edu.au
Harris
Judith
J
Pritchard
Colin W
CW
Coates
John
J
Haque
Sayeed
S
Holder
Roger
R
Bentham
Peter
P
Lendon
Corinne L
CL
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000150:complications; D001526:Behavioral Symptoms / Q000209:etiology / Q000235:genetics*; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D005260:Female; D005838:Genotype; D006801:Humans; D016015:Logistic Models; D008297:Male; D009483:Neuropsychological Tests; D011110:Polymorphism, Genetic; D011569:Psychiatric Status Rating Scales; D011618:Psychotic Disorders / Q000209:etiology / Q000235:genetics*; D044402:Receptor, Serotonin, 5-HT2A / Q000235:genetics*; D044405:Receptor, Serotonin, 5-HT2C / Q000235:genetics*
D044402:Receptor, Serotonin, 5-HT2A; D044405:Receptor, Serotonin, 5-HT2C