Behavioral Genetics of Impulsivity

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DESCRIPTION (provided by applicant): Impulsivity is a common feature of numerous psychological, psychiatric and social problems, including conduct disorder, attention deficit hyperactivity disorder, substance abuse, antisocial personality disorder, criminality and violence. Behavioral genetics studies have consistently demonstrated significant genetic contributions to individual differences in personality traits and behavioral outcomes related to impulsivity, and there is increasing evidence that impulsivity and impulsive aggression may be mediated, in part, by activity of the monoaminergic (serotonin, dopamine and norepinephrine) neurotransmitter systems. However, little is known about the genetic covariance between behavioral and neurobiological phenotypes, or the role of specific environmental influences in the development of impulsivity within a complex natural social system. Proposed here is a longitudinal study that follows related individuals from infancy to adulthood, collects objective, prospective measures of environmental variables and behavioral phenotypes, and concurrently assesses neurobiological variables in a nonhuman primate model appropriate for quantitative behavioral genetics analysis. Subjects for this research are 725 vervet monkeys (Cercopithecus aethiops sabaeus), living in naturally composed social groups in a multigenerational, pedigreed colony that includes full siblings, maternal and paternal half siblings, and dyads of varying degrees of relatedness. The objectives of this investigation are to a) assess the relative contribution of genetic and environmental factors to variation in impulsivity at different life stages, b) to determine the contribution of specific early experiences (maternal style, family social status, peer relationships) to variation in impulsivity, and c) to evaluate the role of monoaminergic neurotransmitter systems in mediating genetic influences on impulsivity. To accomplish these objectives we propose to 1) measure individual differences in impulsivity in standardized situations from one year of age to adulthood, 2) collect objective, prospective data on individual experiences during development, 3) assess longitudinal variation in metabolites of serotonin, dopamine and norepinephrine in cerebrospinal fluid, and 4) identify genetic polymorphisms at loci in serotonergic and dopaminergic pathways (serotonin transporter, tryptophan hydroxylase, dopamine transporter and dopamine receptor DRD4 genes) for use in candidate gene linkage analysis. The proposed research will provide new information on the genetic, environmental and neurobiological contributions to development of individual differences in a dimension of temperament that is a major risk factor for behavioral, psychological and psychiatric problems.