Suicide attempts and the tryptophan hydroxylase gene

Mol Psychiatry. 2001 May;6(3):268-73. doi: 10.1038/


Tryptophan hydroxylase (TPH) is the rate-limiting enzyme of serotonin synthesis. In this case-control study, we investigated whether the TPH gene was a susceptibility factor for suicidal behavior. Seven polymorphisms spanning the entire gene were studied in a case-control study including 231 individuals who had attempted suicide and 281 controls. Significant associations were found between variants in introns 7, 8 and 9 (chi(2) = 11.2, df = 1, P< 0.0008 for the allele distribution; these loci are in complete linkage disequilibrium) and in the 3' noncoding region (chi(2) = 30.94, P = 0.0014) and suicide attempt. The association was strongest for subjects who had attempted suicide by violent means and who had a history of major depression. No significant association was observed between suicide attempts and polymorphisms in the promoter, intron 1 and intron 3. The results presented here, and those of previous studies, suggest that a genetic variant of the 3' part of the TPH gene may be a susceptibility factor for a phenotype combining suicidal behavior, mood disorder and impulsive aggression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Brain Chemistry / genetics*
  • Case-Control Studies
  • Depression / genetics
  • Female
  • Humans
  • Introns
  • Linkage Disequilibrium
  • Male
  • Middle Aged
  • Polymorphism, Genetic*
  • Serotonin / metabolism
  • Suicide, Attempted*
  • Tryptophan Hydroxylase / genetics*
  • Tryptophan Hydroxylase / metabolism
  • Violence


  • Serotonin
  • Tryptophan Hydroxylase