There is evidence indicating that serotonin uptake and density of 5-HT2A receptors are altered in the brain regions of depressed suicide victims and in platelets of depressed suicidal subjects. The present investigation tested the hypothesis that the above changes in serotonergic system in depressed suicide victims are trait rather than state markers and associated with a polymorphism in respective candidate genes. Two functional polymorphic variants of the 5-HT2A receptor gene, a functional polymorphism in the 5′ regulatory region of the 5-HT transporter gene and an intron7 218A/C polymorphism in the tryptophan hydroxylase gene have been determined in genomic DNA obtained from postmortem brain samples of 24 depressed suicide victims and 30 control subjects of the same ethnic background. In a subset of matched subjects, density (Bmax) of 5-HT uptake sites (labelled with 3H-paroxetine) and of 5-HT2A receptors (labelled with 3H-ketanserin) was also determined in the prefrontal cortex. The major finding of this study was a significantly higher frequency of the 5-HT transporter gene long allele (χ2 = 3.86, d.f. = 1, P = 0.049) in depressed suicides. No significant differences of allele frequencies between suicides and controls were observed for the 102T/C polymorphism (χ2 = 0.11, d.f. = 1, P = 0.75) and His452 Tyr polymorphism (χ2 = 1.82, d.f. = 1, P = 0.18) of 5-HT2A receptor gene, and for the tryptophan hydroxylase gene polymorphism (χ2 = 0.42, d.f. = 1, P = 0.52). The density of 5-HT uptake sites tended to be higher in subjects expressing the short allele of 5-HT transporter gene. Our finding provides the first evidence suggesting that a functional polymorphism in the regulatory region of the serotonin transporter gene may be associated with suicidal behavior.
|Number of pages||1|
|Journal||American Journal of Medical Genetics - Neuropsychiatric Genetics|
|Publication status||Published - Nov 6 1998|
ASJC Scopus subject areas
- Psychiatry and Mental health
- Cellular and Molecular Neuroscience