SEROTONIN RELATED GENES AND IMPULSIVE AGGRESSION IN PD

DESCRIPTION (Adapted from applicant's abstract): The purpose of the proposed study is to investigate the genetic contribution to impulsive aggressive behavior in patients with personality disorders, utilizing known polymorphisms in serotonin-related genes. Impulsive aggressive behavior is prevalent in patients with personality disorders and accounts for a substantial portion of the morbidity associated with these disorders. It is logical to investigate the association between genotype in serotonin-related genes and impulsive aggression in patients with personality disorders, in light of the observations that: 1) decreased serotonergic activity in the central nervous system has been demonstrated in personality disordered patients with impulsive aggressive behavior; 2) impulsive aggression has been shown to be at least partially heritable; 3) serotonin-related polymorphisms (variability in genotype) have been described, allowing for the characterization of genotype in individual subjects. In addition, we propose to measure central serotonin function utilizing the prolactin response to fenfluramine to allow for comparisons with both genotype and clinical phenomena. We propose to study 50 impulsive aggressive and 50 non-impulsive aggressive patients with personality disorders. We will characterize their aggressive behavior, identify genotypes in relation to the following genes: tryptophan hydroxylase, the serotonin transporter [SLC6A4] (promotor and intronic), 5-HT 2A [T120C] and 5-HT 2C and access central serotonergic function with the prolactin response to fenfluramine.