Association of polymorphism of serotonin 2A receptor gene with suicidal ideation in major depressive disorder

Abstract

There is evidence indicating that density of 5-HT2A receptors is altered in brain regions of depressed suicide victims and in platelets of suicidal subjects with major depression or schizophrenia. Recent studies have also shown an association between the allele C of 102T/C polymorphism in the 5-HT2A receptor gene and schizophrenia. The present investigation tested the hypothesis that the observed changes in 5-HT2A receptor density in platelets of patients with major depression are a trait rather than state phenomenon and are associated with the 102 C allele in 5-HT2A receptor gene in a sample of 120 patients with major depression and a group of 131 control subjects comparable with respect to age, sex, and ethnic background. The allele and genotype frequencies of 102T/C polymorphism in 5-HT2A receptor gene were compared between patients and control subjects and between suicidal and non-suicidal patient groups. The major finding of this study was a significant association between the 102 C allele in 5-HT2A receptor gene and major depression, chi(2) = 4.5, df = 1, P = 0.03, particularly in patients with suicidal ideation, chi(2) = 8.5, df = 1, P < 0.005. Furthermore, we found that patients with a 102 C/C genotype had a significantly higher mean HAMD item 3 score (indication of suicidal ideation) than T/C or T/T genotype patients. Our results suggest that the 102T/C polymorphism in 5-HT2A receptor gene is primarily associated with suicidal ideation in patients with major depression. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:56-60, 2000.

Gene–environment interaction analysis of serotonin system markers with adolescent depression

“…11 Second, several receptor genes have been examined. For example, 5HT2A has been repeatedly investigated for association with depression, with both positive 12 and negative 13 results, and has also been found to be associated with learned helplessness in rats, an animal model of depression. 14 The C allele at the T102C SNP of the 5HT receptor 2A has also been associated with suicide 15 and suicidal ideation, 12 although again there have also been negative findings.…”

Genetics of suicide

“…However, the genetic findings of associations between 5-HT2A receptor gene variants and suicide have been controversial. Du et al 114 reported an association of the 5-HT2A receptor 102C-allele with suicidal ideation in 78 Canadian patients with major depression (w 2 = 8,5; df = 1; P = 0.005). They found that patients with the CC genotype had significantly higher scores in HAMD item 3 score (indication of suicidal behaviour) than TC or TT genotypes and concluded that the 5-HT2A receptor 102C allele might confer increased risk for suicidality independently of psychiatric diagnosis.…”

“…In the light of the findings of Du et al, 114 several studies have been carried out among different diagnostic groups and different ethnicities. However, no associations were found with suicidal behaviour in the Caucasian population comprising alcoholics with suicidal ideation and previous suicide attempts, 116 schizophrenics with suicidal ideation 117 or suicide attempts.…”

Tryptophan hydroxylase immunoreactivity is altered by the genetic variation in postmortem brain samples of both suicide victims and controls

“…10,11 Recently, Turecki et al 12 have reported that the A-1438G polymorphism of the 5HT2A receptor gene significantly affects the 5HT2A receptor in the prefrontal cortex (Brodmann's area 9), but another study was unable to replicate their results. 13 In an association study, Du et al reported that the C allele of the T102C polymorphism, which is almost completely in disequilibrium with the A-1438G polymorphism, 14 was associated with suicidal ideation in major depressive disorders, 15 although no association was found between these polymorphisms and suicidal behavior itself. 12,16,17 Tryptophan hydroxylase (TPH) is the rate-limiting enzyme in serotonin biosynthesis and has a major function in regulating the serotonergic system.…”