There is remarkable conservation of behavioral traits related to vulnerability for mental illness. Forexample, high trait novelty-seeking in humans is a risk factor for attention deficit/hyperactivity disorderand stimulant dependence, and novelty-seeking is also a heritable trait determined in part by similargenetic mechanisms in other species. This project, designed to bridge the studies of memorymechanisms and response inhibition.components in the Consortium for Neuropsychiatric Phenomics,will evaluate the heritability of a laboratory measures of response inhibition or working memory andnaturalistic measures of novelty-seeking and behavioral impulsivity in an established pedigree of nonhumananimals suitable for quantitative trait linkage analyses of phenotypes exhibiting substantialheritability. High density SNP mapping will focus on regions of strongest linkage and on target regionsdiscovered to associate with similar traits in humans. Subsequent to population-wide screening forphenotypes, groups will be constituted according to extreme deviation from normal on the traits ofinterest (e.g., high novelty-seeking/poor response inhibition), and these groups will be evaluated usingnon-invasive structural and molecular imaging to evaluate the hypothesis that specific modifications indopamine transmission mediate the genotype-phenotype relationships.This project, which is tightly coupled to on-going behavioral genetic studies in healthy people and thosewith psychiatric disorders, is designed to uncover new genetic mechanisms contributing to humanneuropsychiatric disease-related traits, characterize new translational models for these traits andgenerate new insights about the molecular and cellular phenotypes intermediate between genotypesand complex behavioral phenotypes.
Showing the most recent 10 out of 24 publications
