Suicidality and 5-hydroxyindoleacetic acid concentration associated with a tryptophan hydroxylase polymorphism

Arch Gen Psychiatry. 1994 Jan;51(1):34-8. doi: 10.1001/archpsyc.1994.03950010034005.


Background: To examine whether the tryptophan hydroxylase (TPH) gene, which codes for the rate-limiting enzyme in the biosynthesis of serotonin, may be a factor influencing serotonin turnover and behaviors controlled by serotonin.

Methods: Using a polymerase chain reaction-based method, TPH genotype was determined in DNA samples from 56 impulsive and 14 nonimpulsive, alcoholic, violent offenders and 20 healthy volunteers.

Results: In the behaviorally extreme impulsive group, we observed a significant association between TPH genotype and cerebrospinal fluid 5-hydroxyindoleacetic acid (5-HIAA) concentration. No association of TPH genotype with impulsive behavior was detected. The polymorphism was also associated with a history of suicide attempts in all violent offenders, independent of impulsivity status and cerebrospinal fluid 5-HIAA concentration.

Conclusion: In some individuals, a genetic variant of the TPH gene may influence 5-HIAA concentration in the cerebrospinal fluid and predisposition to suicidal behavior.

MeSH terms

  • Adult
  • Alcoholism / cerebrospinal fluid
  • Alcoholism / genetics
  • Alcoholism / metabolism
  • Antisocial Personality Disorder / cerebrospinal fluid
  • Antisocial Personality Disorder / genetics
  • Antisocial Personality Disorder / metabolism
  • Disruptive, Impulse Control, and Conduct Disorders / cerebrospinal fluid
  • Disruptive, Impulse Control, and Conduct Disorders / genetics
  • Disruptive, Impulse Control, and Conduct Disorders / metabolism
  • Genotype
  • Humans
  • Hydroxyindoleacetic Acid / cerebrospinal fluid*
  • Male
  • Polymerase Chain Reaction
  • Polymorphism, Genetic
  • Serotonin / biosynthesis
  • Serotonin / metabolism
  • Serotonin / physiology
  • Suicide / psychology
  • Suicide / statistics & numerical data*
  • Suicide, Attempted / psychology
  • Suicide, Attempted / statistics & numerical data
  • Tryptophan Hydroxylase / genetics*
  • Violence


  • Serotonin
  • Hydroxyindoleacetic Acid
  • Tryptophan Hydroxylase