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David A. Nielsen, PhD; David Goldman, MD; Matti Virkkunen, MD; Riitta Tokola, MD; Robert Rawlings, MS; Markku Linnoila, MD, PhD

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

Abstract
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.

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).

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