The 5-HTTPR*S/*L polymorphism and aggressive behavior in Alzheimer disease

Background: Aggressive behavior in Alzheimer disease (AD) has been linked to dysfunction of serotonin neurotransmission. Homozygosity for the long variant (*L) of an identified biallelic polymorphism of the serotonin transporter promoter region (5-HTTPR) is associated with increased expression of the transporter protein and increased speed of response to serotonin reuptake inhibitor treatment. Objective: To determine whether the *L/*L genotype and the *L allele are associated with an increased risk of aggressive symptoms in patients with AD. Design: Case-control study. Setting: University hospital geriatric psychiatry inpatient program and Alzheimer disease research center. Subjects: Fifty-eight patients with AD with a history of aggressive behavior and 79 never-aggressive patients with AD with comparable severity of cognitive impairment. Main Outcome Measures: The 5-HTTPR genotype and allele frequency. Results: The *L/*L genotype was significantly associated with aggression in patients with AD (odds ratio, 2.8; 95% confidence interval, 1.2-6.5). Similar results were obtained for *L allele frequency. Conclusion: The 5-HTTPR*L allele and *L/*L genotype may predispose patients with AD to develop aggressive behavior.