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


CONCLUSIONS
In some individuals, a genetic variant of the TPH gene may influence 5-HIAA concentration in the cerebrospinal fluid and predisposition to suicidal behavior.
Nielsen
D A
DA
Laboratory of Neurogenetics, National Institute on Alcohol Abuse and Alcoholism, Bethesda, Md.
Goldman
D
D
Virkkunen
M
M
Tokola
R
R
Rawlings
R
R
Linnoila
M
M
D000328:Adult; D000437:Alcoholism / Q000134:cerebrospinal fluid / Q000235:genetics / Q000378:metabolism; D000987:Antisocial Personality Disorder / Q000134:cerebrospinal fluid / Q000235:genetics / Q000378:metabolism; D007174:Disruptive, Impulse Control, and Conduct Disorders / Q000134:cerebrospinal fluid / Q000235:genetics / Q000378:metabolism; D005838:Genotype; D006801:Humans; D006897:Hydroxyindoleacetic Acid / Q000134:cerebrospinal fluid*; D008297:Male; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012701:Serotonin / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology; D013405:Suicide / Q000523:psychology / Q000706:statistics & numerical data*; D013406:Suicide, Attempted / Q000523:psychology / Q000706:statistics & numerical data; D014365:Tryptophan Hydroxylase / Q000235:genetics*; D014754:Violence
D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D014365:Tryptophan Hydroxylase