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 victi ms mid in platelets of depressed suicidal subjects. The present investigati on rested the hypothesis that these changes in the serotonergic system in d epressed 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 fun ctional polymorphism) of the 5-HT2A receptor gene and a functional polymorp hism in the 5' regulatory region of the 5-HT transporter gene, have been de termined in genomic DNA obtained from postmortem brain samples of 24 depres sed 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 frequen cy 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 an d controls were observed for the 102T/C polymorphism and His(452)Tyr polymo rphism 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 tr ansporter gene. Furthermore, there was a significant difference in serotoni n transporter binding sites between the genotype S/S and combined genotype S/L and L/L. Conclusions: Our finding provides the first evidence suggestin g that a functional polymorphism in the regulatory region of serotonin tran sporter gene may be associated with suicide in depressed subjects. (C) 1999 Society of Biological Psychiatry.