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The 5-HTTPR*S/*L Polymorphism and Aggressive Behavior in Alzheimer Disease
Danielle L. Sukonick, BA;
Bruce G. Pollock, MD, PhD;
Robert A. Sweet, MD;
Benoit H. Mulsant, MD;
Jules Rosen, MD;
William E. Klunk, MD, PhD;
Kari B. Kastango, MS;
Steven T. DeKosky, MD;
Robert E. Ferrell, PhD
Arch Neurol. 2001;58:1425-1428.
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.
From the Division of Geriatrics and Neuropsychiatry, Department of
Psychiatry (Mss Sukonick and Kastango and Drs Pollock, Sweet, Mulsant, Rosen,
Klunk, and DeKosky), Department of Neurology, School of Medicine (Dr DeKosky),
and Department of Human Genetics, Graduate School of Public Health (Dr Ferrell),
University of Pittsburgh, Pittsburgh, Pa; and the Geriatric Research, Education,
and Clinical Center, Veterans Affairs Pittsburgh Health Care System (Dr Mulsant).
Dr Mulsant has received grant or research support from the National Institute
of Mental Health, AstraZeneca, Inc, Janssen Pharmaceutica, Pfizer, Inc/Eisai
Pharmaceuticals, and GlaxoSmithKline; is a consultant to AstraZeneca, Inc,
Eli Lilly and Company, Janssen Pharmaceutica, Pfizer, Inc, and GlaxoSmithKline;
is on the speaker's bureau for AstraZeneca, Inc, Janssen Pharmaceutica, Pfizer,
Inc/Eisai Pharmaceuticals, Searle, and GlaxoSmithKline; owns stock in Akzo-Nobel,
Biogen, Inc, Celsion Corporation, Elan Corporation, Forest Laboratories, Inc,
and Immune Response Corporation; is a major stock holder in Biogen, Inc; and
has received honoraria from AstraZeneca, Inc, Eli Lilly and Company, Janssen
Pharmaceutica, Pfizer, Inc/Eisai Pharmaceuticals, Organon, Searle, and GlaxoSmithKline.
Corresponding author and reprints: Robert A. Sweet, MD, Western Psychiatric
Institute and Clinic, 3811 O'Hara St, Pittsburgh, PA 15213 (e-mail:
SweetRA{at}MSX.UPMC.EDU).
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