Abstract # 200:

Scheduled for Saturday, August 19, 2006 09:00 AM-09:30 AM: Session 17 (Regency East #1) Oral Presentation


FUNCTIONAL VARIANTS IN THE CRH AND NPY GENES INCREASE STRESS REACTIVITY AMONG INFANT RHESUS MACAQUES (Macaca mulatta)

C. S. Barr1, S. G. Lindell1, M. L. Schwandt1, R. L. Dvoskin1, M. Gupte1, T. K. Newman1, S. J. Suomi2 and J. D. Higley1
1NIH/NIAAA, PO Box 529, Poolesville, MD 20837, USA, 2NIH/NICHD
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     Corticotropin Releasing Hormone (CRH) and Neuropeptide Y (NPY) are opposing neuropeptides that regulate emotional and endocrine stress responses. Whereas CRH produces anxiety and activates the hypothalamic-pituitary-adrenal (HPA) axis, NPY is anxiolytic and counteracts the actions of CRH. We have located polymorphisms within glucocorticoid response elements in both the rhCRH and rhNPY regulatory regions, and in vitro studies demonstrate that these variants alter steroid responsivity of the rhCRH and rhNPY promoters. Rhesus macaques were scored behaviorally at baseline and following stress, at which times blood was also sampled for assessment of HPA axis function. Factor analyses were performed using mother-infant and maternal separation-induced behaviors, and the effects of rhCRH and rhNPY variants on rotated factor scores and HPA axis measures were analyzed by ANOVA (P< 0.05). Consistent with the role of glucocorticoids in the tonic feedback regulation of HPA axis function, basal HPA axis activity was higher among infants with the rhCRHA2 haplotype. Infants with the CRH-A2 haplotype were also more solicitous of maternal contact and less independent. Carriers of the NPY variant exhibited higher HPA axis responses to acute stress, but only at first exposure. There was a gene dosage effect with regard to separation-induced behavior, with the minor allele being associated with increased reactivity to stress, although this diminished with repeated stress exposure. Genetic variation at these loci influence stress responsivity and, therefore, may contribute to individual differences in stress vulnerability or resiliency in nonhuman primates.