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Suicidality and 5-hydroxyindoleacetic acid concentration associated with a tryptophan hydroxylase polymorphism
D A Nielsen1, D Goldman, M Virkkunen
1Laboratory of Neurogenetics, National Institute on Alcohol Abuse and Alcoholism, Bethesda, Md.
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.