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Letter to the Editor   |    
Levels of Serotonin Receptor 2A Higher in Suicide Victims?
PAVEL D. HRDINA, M.D., PH.D.; LISHENG DU, PH.D.
Am J Psychiatry 2001;158:147-a-148. doi:10.1176/appi.ajp.158.1.147-a

To the Editor: Gustavo Turecki, M.D., Ph.D., and colleagues (1) recently suggested that an increase in the density of serotonin receptor 2A (5-HTR2A) in the brains of suicide victims (2, 3) may be genetically mediated. They called for a reproduction of their genetic findings in an independent study group of similar composition. We investigated the T102C polymorphism in the 5-HTR2A gene in brain samples (Brodmann’s area 9 of the cortex) from 24 depressed suicide victims and 31 matched comparison subjects and, in agreement with Dr. Turecki et al., found no significant differences in allelic or genotypic distribution between suicide victims and comparison subjects (4). In a subset of 10 depressed suicide victims and 15 comparison subjects, the density of 5-HTR2A was significantly higher than in the comparison subjects, but there were no differences in receptor densities among the three genotypes of 5-HTR2A: T/T, T/C, and C/C. We think this might have been because of our small group size—in particular, a low level of binding values in the T/T group.

We re-evaluated the phenotypic-genotypic relationship in a larger group (17 depressed suicide victims and 35 comparison subjects) of the same provenience and found that 5-HTR2A binding in the brains of suicide victims carrying the T allele was higher (mean=153 fmol/mg protein, SD=20) than that of their respective comparison subjects (mean=114 fmol/mg protein, SD=13) (unpublished data). However, C allele carriers who committed suicide also had higher levels of 5-HTR2A binding (mean=159 fmol/mg protein, SD=18) than did the comparison subjects carrying the same allele (mean=119 fmol/mg protein, SD=12). A two-way analysis of variance revealed a significant main effect of suicide on 5-HTR2A binding levels (F=6.93, df=1, 100, p<0.01) but no significant effect on the two alleles of the 5-HTR2A gene (F=0.20, df=1, 100, p=0.65).

We have thus confirmed the observation by Dr. Turecki et al. of no differences in 5-HTR2A gene allelic or genotypic distribution between suicide victims and comparison subjects, as well as the effect of suicide on 5-HTR2A densities in the frontal cortex. Our data agree with the result of their stepwise logistic regression. It was conducted with suicide as the main outcome and indicated that 5-HTR2A binding, but not 5-HTR2A genetic variation, was significant in predicting suicide. However, we were unable to confirm their finding that allelic variation significantly affects 5-HTR2A densities in suicide victims and comparison subjects; we thus cannot support their suggestion that 5-HTR2A binding is genetically determined by an allelic variation in the T102C polymorphism of the 5-HTR2A gene.

Turecki G, Brière R, Dewar K, Antonetti T, Lesage AD, Séguin M, Chawky N, Vanier C, Alda M, Joober R, Benkelfat C, Rouleau GA: Prediction of level of serotonin 2A receptor binding by serotonin receptor 2A genetic variation in postmortem brain samples from subjects who did or did not commit suicide. Am J Psychiatry 1999; 156:1456–  1458
 
Stanley M, Mann JJ: Increased serotonin-2 binding sites in frontal cortex of suicide victims. Lancet  1983; 1:214–216
[PubMed]
 
Hrdina PD, Demeter E, Vu TB, Sotonyi P, Palkovits M:5-HT uptake sites and 5-HT2 receptors in brain of antidepressant-free suicide victims/depressives: increase in 5-HT2 sites in cortex and amygdala. Brain Res  1993; 614:37–44
 
Du L, Faludi G, Palkovits M, Demeter E, Bakish D, Lapierre Y, Sotonyi P, Hrdina PD: Frequency of long allele in serotonin transporter gene is increased in depressed suicide victims. Biol Psychiatry  1999; 46:196–201
[PubMed]
[CrossRef]
 
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References

Turecki G, Brière R, Dewar K, Antonetti T, Lesage AD, Séguin M, Chawky N, Vanier C, Alda M, Joober R, Benkelfat C, Rouleau GA: Prediction of level of serotonin 2A receptor binding by serotonin receptor 2A genetic variation in postmortem brain samples from subjects who did or did not commit suicide. Am J Psychiatry 1999; 156:1456–  1458
 
Stanley M, Mann JJ: Increased serotonin-2 binding sites in frontal cortex of suicide victims. Lancet  1983; 1:214–216
[PubMed]
 
Hrdina PD, Demeter E, Vu TB, Sotonyi P, Palkovits M:5-HT uptake sites and 5-HT2 receptors in brain of antidepressant-free suicide victims/depressives: increase in 5-HT2 sites in cortex and amygdala. Brain Res  1993; 614:37–44
 
Du L, Faludi G, Palkovits M, Demeter E, Bakish D, Lapierre Y, Sotonyi P, Hrdina PD: Frequency of long allele in serotonin transporter gene is increased in depressed suicide victims. Biol Psychiatry  1999; 46:196–201
[PubMed]
[CrossRef]
 
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