PRIORITY COMMUNICATION Aggression and Anger-Related Traits Associated With a Polymorphism of the Tryptophan

activity correlates inversely with human aggressive behav-ior, and individual differences in aggressive disposition are at least partially heritable. This study was conducted to evaluate the possible association between measures of antagonistic behavior and an intronic polymorphism of the gene coding for tryptophan hydroxylase (TPH), the rate-limiting enzyme in serotonin biosynthesis. Methods: Locally recruited men and women (n 5 251) were genotyped for the A218C polymorphism located in intron 7 of the TPH gene. All subjects were administered standard interview and questionnaire indices of aggres-sion and anger-related traits of personality; in a portion of subjects, CNS serotonergic activity was assessed by neu-ropsychopharmacologic challenge (prolactin response to fenfluramine hydrochloride). Results: Persons having any TPH U allele scored signif-icantly higher on measures of aggression and tendency to experience unprovoked anger and were more likely to report expressing their anger outwardly than individuals homozygous for the alternate L allele. In men, but not women, peak prolactin response to fenfluramine was also attenuated among subjects having any U allele, relative to LL homozygotes. Conclusions: Individual differences in aggressive dispo-sition are associated with an intronic polymorphism of the TPH gene in a nonpatient sample of community-derive