Objective: The authors attempted to understand the role of two serotonin system genes, HTR2A and SLC6A4, on psychosis associated with Alzheimer dementia (AD).
Method: Relevant published studies were assessed, and their data were meta-analyzed to determine pooled odds ratios (ORs) that were assessed for heterogeneity. Additional robustness checks were performed to assess for publication bias and any undue influence from a single study. Finally, the number of studies required to invalidate positive findings was determined.
Results: The C allele of HTR2A emerged as a significant risk factor for psychosis, with an allelic OR of 2.191 that increased to 5.143 for the homozygous CC genotype. The SLC6A4 polymorphism was not reliably associated with either psychosis or delusions.
Conclusions: The strong and robust positive association that was noted between the C allele of HTR2A and psychosis suggests that the HTR2A T102C polymorphism is a significant risk factor for psychosis of AD.