Abstract # 5979 Poster # 170:

Scheduled for Sunday, September 14, 2014 07:00 PM-09:00 PM: Session 22 (Decatur B) Poster Presentation


A C-TO-T SNP IN THE PROMOTER REGION OF THE RHESUS MACAQUE (MACACA MULATTA) CRH GENE INTERACTS WITH NURSERY REARING RESULTING IN PTSD-LIKE DYSREGULATION OF THE HPA AXIS AND DISRUPTED HPA AXIS HABITUATION TO REPEATED STRESS

S. A. Aston1, P. H. O'Connell1, J. Shackett1, A. N. Sorenson1, M. L. Schwandt2, S. G. Lindell2, S. J. Suomi2, C. S. Barr2 and J. D. Higley1
1Brigham Young University, Department of Psychology, 1042 SWKT, Provo, UT 84606, USA, 2National Institutes of Health, NICHD, NIAAA
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     Introduction: A single nucleotide polymorphism (SNP) in the rhesus macaque corticotropin-releasing hormone (CRH) gene, CRH-248 C>T, disrupts functioning of the hypothalamic-pituitary-adrenal (HPA) axis. We investigated the effect of CRH-248 genotype and rearing experiences on HPA axis activity in a study modeling features of PTSD. Methods: Infants heterozygous for the CRH-248 SNP (C/T) or homozygous for the common variant (C/C), were mother reared or nursery reared for the first six months of life. Blood samples were taken at one, two, three, and four months of age, and again at six months of age following 4, four-day social separations. Samples were assayed for ACTH and cortisol. Results: Repeated measures ANOVAs showed significant ACTH, cortisol, and ratio of cortisol to ACTH gene X environment interactions (p=0.027, p=0.041, p=0.030). C/T, NR subjects exhibited higher ACTH, lower cortisol, and lower ratios of cortisol to ACTH than C/C and C/T MR subjects. C/C, NR subjects exhibited lower ACTH, and a higher ratio of cortisol to ACTH than C/C and C/T MR subjects. Analyses of the separation data showed a significant 3-way, gene x environment x time interaction (p=0.045), with only C/C MR and NR subjects showing habituation. Discussion: Possession of the CRH C/T genotype results in dysregulated HPA axis functioning, and our findings in NR subjects show that C/T subjects show an HPA Axis pattern reported in individuals with PTSD.