This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The overall goal of this study is to take a novel approach, using a nonhuman primate model, to identify genes that may underlie the development of two common psychiatric illnesses, anxiety and depression. These disorders are common psychiatric illnesses of both childhood and adulthood, are highly comorbid, and strongly aggregate within families. There is some evidence that the overlapping sets of genes may affect liability to both kinds of disorders. However, the complexity of these disorders argues it will be difficult to determine their genetic underpinnings. We plan to study the genetic underpinnings of behaviors in rhesus monkeys that parallel several interrelated behavioral and temperamental traits linked to anxiety disorders and depression in humans, including fearfulness, behavioral inhibition, propensity towards distress, and reactivity. In addition, we will evaluate the genetic basis of physiological attributes associated with anxiety and depression, specifically blunted growth hormone (GH) responsiveness to pharmacological stimulation, activity of the HPA axis, and CSF neurotransmitter levels. This proposal is particularly timely in that increased evidence supporting these behavioral and physiological measures as markers of an underlying predisposition to develop anxiety and depression in humans has recently been published, and we have recently found that in young infant rhesus monkeys there is a strong correlation between low GH responsiveness and behavioral inhibition. These measures also show a high degree of heritability.
The specific aims of the study include (1) phenotyping a large kindred of rhesus monkeys using four standardized tests of anxious, fearful and inhibited behaviors, and a clinical protocol for testing GH and CRH responsiveness to stimulation, and measuring CSF monoamine metabolite levels, (2) a genome-wide scan using 300 microsatellite polymorphisms, (3) identification of candidate linkage regions, and (4) screening candidate genes. This project has been developed as a collaborative effort between investigators at three institutions, in order to bring together a team with expertise in assessment of nonhuman primate behavior and physiological measurements, QTL analysis in nonhuman primates, and large scale genomics research. Dr. Rogers of the SNPRC is performing all genotyping and molecular analysis.
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