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January 1994

Suicidality and 5-Hydroxyindoleacetic Acid Concentration Associated With a Tryptophan Hydroxylase Polymorphism

Author Affiliations

From the Laboratories of Neurogenetics (Dr Nielsen and Dr Goldman) and Clinical Studies (Dr Linnoila and Mr Rawlings), Division of Intramural Clinical and Biological Research, National Institute on Alcohol Abuse and Alcoholism, Bethesda, Md, and the Department of Psychiatry, University of Helsinki (Finland) (Drs Virkkunen and Tokola).

Arch Gen Psychiatry. 1994;51(1):34-38. 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.

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