Frequency of long allele in serotonin transporter gene is increased in depressed suicide victims

Background: There is evidence indicating that serotonin uptake and density of 5-HT2A receptors are altered in brain regions of depressed suicide victims mid in platelets of depressed suicidal subjects. The present investigation rested 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 poly morphism and His(452)Tyr 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 (B-max) of 5-HT uptake sites (labeled with H-3-paroxetine) and of 5-HT2A receptors (labeled with H-3-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 (chi(2) = 3.9, df = 1; p = .048) in depressed suicides. No significant differences between suicides and controls were observed for the 102T/C polymorphism and His(452)Tyr polymorphism of 5-HT2A receptor gene. The density of H-3-paroxetine binding sires 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 genotype 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. (C) 1999 Society of Biological Psychiatry.