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

Arch Neurol. 2001 Sep;58(9):1425-8. doi: 10.1001/archneur.58.9.1425.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Aggression*
  • Alzheimer Disease / genetics*
  • Alzheimer Disease / psychology
  • Carrier Proteins / genetics*
  • Case-Control Studies
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease
  • Genotype
  • Humans
  • Male
  • Membrane Glycoproteins / genetics*
  • Membrane Transport Proteins*
  • Nerve Tissue Proteins*
  • Polymorphism, Genetic*
  • Promoter Regions, Genetic / genetics*
  • Serotonin Plasma Membrane Transport Proteins


  • Carrier Proteins
  • Membrane Glycoproteins
  • Membrane Transport Proteins
  • Nerve Tissue Proteins
  • SLC6A4 protein, human
  • Serotonin Plasma Membrane Transport Proteins