Background
The serotonin transporter (5-HTT)-linked polymorphic region (5-HTTLPR) has two frequent
alleles, designated long (L), and short (S). The S allele is associated with lower
levels of 5-HTT mRNA and lower 5-HTT expression in human cell lines. A functional
single nucleotide variant was detected within L, designated LA and LG. Only LA is associated with high levels of in vitro 5-HTT expression, whereas LG is low expressing and more similar to S. We examined the possible influence of the
long (A/G) variant on 5-HTT density in the living human brain using 3-(11)C-amino-4-(2-dimethylaminomethylphenyl-sulfanyl)
benzonitrile ([11C]DASB) positron emission tomography.
Methods
The 5-HTT binding potential (5-HTT BP), an index of 5-HTT density, was found in 43
healthy subjects genotyped for 5-HTTLPR long (A/G), and in an ethnically homogenous
subsample of 30 Caucasian-Canadians.
Results
The LA/LA was associated with higher 5-HTT BP in putamen (p = .026, not corrected). This association became stronger in the Caucasian subsample
(p = .004) and was significant even after correcting for multiple comparisons.
Conclusions
The 5-HTTLPR long (A/G) polymorphism influences 5-HTT density leading to higher putamen
5-HTT BP in healthy LA/LA carriers of Caucasian ancestry. This finding extends the role of this polymorphism
from in vitro reports of higher 5-HTT expression with the LA/LA genotype into in vivo brains of healthy human subjects.
Key Words
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Article info
Publication history
Published online: January 09, 2007
Accepted:
September 25,
2006
Received in revised form:
September 21,
2006
Received:
June 16,
2006
Identification
Copyright
© 2007 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
