Tryptophan hydroxylase immunoreactivity is altered by the genetic variation in postmortem brain samples of both...

Several lines of evidence suggest that a partly genetically controlled serotonergic dysfunction is involved in the biological pathogenesis of suicide. In this study, we measured tryptophan hydroxylase (TPH) immunoreactivity as a pre-synaptic marker, and serotonin receptor 2A (5HT2A receptor) density as a post-synaptic marker in the serotonergic system in 10 postmortem brains of suicide victims. We also examined whether TPH gene polymorphisms (A218C and A-6526G polymorphisms) could affect TPH immunoreactivity and 5HT2A receptor gene polymorphism (A-1438G polymorphism) could affect 5HT2A receptor density in 28 postmortem brain samples. No significant differences were found in TPH immunoreactivity or 5HT2A receptor density between suicide victims and controls. The AA genotype of the A218C polymorphism of the TPH gene showed higher TPH immunoreactivity along with lower 5HT2A receptor density than did any other genotypes in the postmortem brains of both suicide victims and controls. Our findings suggest that the A218C polymorphism of the TPH gene can be expected to provide new insights not only for neurobiological studies of suicide, but also for research into the behavioral characteristics that may be associated with serotonergic dysfunction.