Human Molecular Genetics, Vol 7, 1507-1509, Copyright © 1998 by Oxford University Press
C Holmes, MJ Arranz, JF Powell, DA Collier and S Lovestone
The psychopathology of Alzheimer's disease (AD) is varied and includes both
behavioural and psychological symptoms. Behavioural and psychological
symptoms are common and contribute to the difficulties experienced by
carers. However, the mechanism whereby these symptoms occur in some
individuals with AD is not understood. We hypothesized that common genetic
polymorphisms in neurotransmitter systems are risk factors for these
symptoms in the course of AD. A total of 211 subjects from a
population-based prospective study of psychopathology within late-onset AD
were genotyped for the 5-HT2A receptor polymorphism 102- T/C and the 5-HT2C
receptor polymorphism Cys23Ser. Associations were found between the
presence of the C102 allele and the presence of visual (Fisher's exact
test, one-tailed, P = 0.003) and auditory hallucinations (Fisher's exact
test, one-tailed, P = 0.004) and between the presence of the Ser23 allele
and visual hallucinations (chi2 = 7.5, df = 1, P = 0.006) (P = 0.03, 0.04
and 0.06, respectively, after Bonferroni correction). In addition, there
was an association between the Cys23Ser polymorphism and hyperphagia (chi2
= 6.7, df = 2, P = 0.03) (P = 0.3 after Bonferroni correction). We conclude
that common 5- HT2A and 5-HT2C genetic polymorphisms previously showing
only weak associations with psychotic illness are associated with psychotic
symptoms in AD but are clinically silent until the onset of the
neurodegenerative process.
ARTICLES
5-HT2A and 5-HT2C receptor polymorphisms and psychopathology in late onset Alzheimer's disease
Department of Neuroscience, Institute of Psychiatry, De Crespigny Park, London SE5 8AF, UK. c.holmes@iop.bpmf.ac
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