Abstract
Background: There is evidence indicating that serotonin uptake and density of 5-HT2A receptors are altered in brain regions of depressed suicide victims and in platelets
of depressed suicidal subjects. The present investigation tested the hypothesis that
these changes in the serotonergic system in depressed suicide victims are trait rather
than state markers and associated with a polymorphism in respective candidate genes.
Methods: Two polymorphic variants (102T/C polymorphism and His452Tyr functional polymorphism) of the 5-HT2A receptor gene and a functional polymorphism in the 5′ regulatory region of the 5-HT
transporter gene, have been determined in genomic DNA obtained from postmortem brain
samples of 24 depressed suicide victims and 31 control subjects of the same ethnic
background. In a subset of subjects, density (Bmax) of 5-HT uptake sites (labeled with 3H-paroxetine) and of 5-HT2A receptors (labeled with 3H-ketanserin) was also determined in prefrontal cortex samples.
Results: The major finding of this study was a significantly higher frequency of the
5-HT transporter gene long (L) allele (χ2 = 3.9, df = 1; p = .048) in depressed suicides. No significant differences between
suicides and controls were observed for the 102T/C polymorphism and His452Tyr polymorphism of 5-HT2A receptor gene. The density of 3H-paroxetine binding sites tended to be higher in subjects expressing the short (S)
allele of 5-HT transporter gene. Furthermore, there was a significant difference in
serotonin transporter binding sites between the genotype S/S and combined genotypes
S/L and L/L.
Conclusions: Our finding provides the first evidence suggesting that a functional
polymorphism in the regulatory region of serotonin transporter gene may be associated
with suicide in depressed subjects.
Keywords
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Article info
Publication history
Accepted:
November 27,
1998
Received in revised form:
November 16,
1998
Received:
July 15,
1998
Identification
Copyright
© 1999 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
