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

by
Du L, Faludi G, Palkovits M, Demeter E,
Bakish D, Lapierre YD, Sotonyi P, Hrdina PD
Institute of Mental Health Research
at Royal Ottawa Hospital, Ontario, Canada.
Biol Psychiatry 1999 Jul 15; 46(2):196-201


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 (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 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.
LSD
SSRIs
5-HT2
5-HT3
5-HT4
5-H2c
5-HT1a
5-HT2a
Serotonin
SSRIs and 5-HT1b
Suicide: biochemical pathways
Serotonin, the HPA axis and suicide
The 5-HT2 family of serotonin receptors
5-HT2a inverse agonists as antipsychotics
Depression, SSRIs and the serotonin 5-HT2 receptors
5-HT2a antagonists as antidepressants and antipsychotics


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