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Serotonergic dysfunction doesnt cause suicide

Several lines of evidence suggest that a partially genetically controlled serotonergic dysfunction is involved in the biological pathogenesis of suicide. To investigate the involvement of serotonergic dysfunction in suicide victims, Japanese scientists measured the protein level of tryptophan hydroxylase (TPH), the rate-limiting enzyme in serotonin biosynthesis, as a pre-synaptic maker. They also measured serotonin receptor 2A (5HT2A receptor) density as a post-synaptic marker in the serotonergic system in postmortem brains of 10 suicide victims and 12 controls. In addition, to clarify the genetic involvement in serotonergic function, the authors examined whether the variations of the TPH gene could affect TPH protein level, and whether those of the 5HT2A receptor gene could affect 5HT2A receptor density in 28 postmortem brain samples.

No significant differences were found in TPH protein level or 5HT2A receptor density between suicide victims and controls. There was a significant negative correlation, however, between TPH protein level and 5HT2A receptor density. The variation of the TPH gene (the A218C polymorphism: a single base transition, A to C) had a significant influence on both TPH protein level and 5HT2A receptor binding. The AA genotype of the A218C polymorphism of the TPH gene showed higher TPH protein level along with lower 5HT2A receptor density than did any other genotypes in the postmortem brains of both suicide victims and controls.

The major finding of the study was that the A218C polymorphism of the TPH gene altered TPH protein level in postmortem brain samples from both those who did commit suicide and those who did not. There was no change in TPH protein level or 5HT2A receptor density in the postmortem brain of the suicide victims, compared to the controls. These results together suggest that the A218C polymorphism of the TPH gene does not play a major role in the biological suicidality, but seems to be involved in the seroton
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Contact: Aimee Midei
molecularpsychiatry@mednet.ucla.edu
310-206-6739
Molecular Psychiatry
16-Dec-2002


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