Background: Psychotic symptoms in subjects with Alzheimer disease (AD+psychosis, AD+P) are a marker for a distinct phenotype characterized by more rapid cognitive and functional decline and a liability to aggressive behaviors. We recently found that AD subjects homozygous for long alleles (l) of an insertion/deletion polymorphism in the promoter region of the serotonin transporter (5-HTTPR) had elevated rates of aggressive behavior. Objective: To examine whether the 5-HTTPR ll genotype confers an increased risk of AD+P, and of the combined AD+P/aggressive phenotype. Methods: The 5-HTTPR genotype was determined in 332 subjects diagnosed with possible or probable AD. All subjects received structured psychiatric assessments and were categorized with regard to their history of aggressive behaviors and psychotic symptoms. Results: Consistent with other reports, AD+P was associated with a significant increased risk for aggressive behavior. AD+P and aggression were both significantly associated with 5-HTTPR ll genotype and with an increased l allele frequency. Subjects with the combined behavioral phenotype (AD+P and aggressive behavior) had the highest rate of ll genotype and highest l allele frequency. Conclusion: The 5-HTTPR l allele appears to confer risk for the combined AD+P/aggressive phenotype. Confirmation of this association in a similar behaviorally well-characterized independent sample is needed.
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