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

• Published in: Biological psychiatry (1969) 1999-07, Vol.46 (2), p.196-201
• Main Authors: Du, Lisheng, Faludi, Gábor, Palkovits, Miklós, Demeter, Elizabeth, Bakish, David, Lapierre, Yvon D, Sótonyi, Peter, Hrdina, Pavel D
• Format: Article
• Language: English
• Subjects: Adult; Adult and adolescent clinical studies; Aged; Alleles; association; Binding Sites; Biological and medical sciences; Biological Transport - genetics; candidate genes (serotonin transporter and serotonin 2A receptor); Carrier Proteins - genetics; Cell Count; Culture Techniques; Depressed suicide; Depressive Disorder - genetics; Depressive Disorder - psychology; DNA - analysis; Female; Gene Expression - genetics; Gene Frequency - genetics; Genetic Variation - genetics; Humans; Male; Medical sciences; Middle Aged; polymorphism; Polymorphism, Genetic - genetics; Prefrontal Cortex - cytology; Prefrontal Cortex - metabolism; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Serotonin - genetics; Serotonin - metabolism; Suicide; Suicide - psychology
• ISSN: 0006-3223; 1873-2402
• DOI: 10.1016/S0006-3223(98)00376-X

Background: There is evidence indicating that serotonin uptake and density of 5-HT 2A 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 His 452Tyr functional polymorphism) of the 5-HT 2A 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 3H-paroxetine) and of 5-HT 2A 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 (χ 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 452Tyr polymorphism of 5-HT 2A 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.