Association between the tryptophan hydroxylase gene and manic-depressive illness

Arch Gen Psychiatry. 1998 Jan;55(1):33-7. doi: 10.1001/archpsyc.55.1.33.


Background: Genes encoding proteins involved in serotonergic metabolism are major candidates in association studies of mood disorders and suicidal behavior. This association study explores whether the tryptophan hydroxylase (TPH) gene, which codes for the rate-limiting enzyme of serotonin biosynthesis, is a susceptibility factor for manic-depressive illness, with or without a history of suicide attempts.

Methods: The TPH intron 7 A218C polymorphism was determined using a polymerase chain reaction-based method in DNA samples from 152 patients with bipolar disorder and 94 healthy control subjects.

Results: There was a significant association between TPH genotypes and manic-depressive illness. Among patients with bipolar disorder, no association was found between TPH alleles and suicidal behavior.

Conclusions: This result suggests the involvement of the TPH gene in susceptibility to manic-depressive illness. This preliminary result requires confirmation in further groups of patients and controls.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alleles
  • Bipolar Disorder / enzymology
  • Bipolar Disorder / genetics*
  • Bipolar Disorder / psychology
  • Disease Susceptibility / enzymology
  • Female
  • Gene Frequency
  • Genetic Markers
  • Genotype
  • Humans
  • Introns
  • Male
  • Middle Aged
  • Polymorphism, Genetic
  • Serotonin / biosynthesis
  • Suicide / psychology
  • Suicide, Attempted / psychology
  • Suicide, Attempted / statistics & numerical data
  • Tryptophan Hydroxylase / genetics*
  • Tryptophan Hydroxylase / physiology
  • Violence / psychology


  • Genetic Markers
  • Serotonin
  • Tryptophan Hydroxylase