Patrick O’Connell, Brigham Young University
Social and Behavioral Sciences
Studies show that the CRH gene has several variants that are associated with psychopathological disorders and dysregulation of the HPA system, including a single nucleotide polymorphism (SNP) located on the promotor region (201 C/T). In rhesus macaques there is a orthologous SNP in the promoter region of the corticotrophin releasing hormone gene, CRH-248 C/T, that up-regulates the production of corticotrophin releasing hormone (CRH), inhibits the down-regulation of CRH expression in the presence of glucocorticoids, and is related to stress-induced alcohol consumption (Barr 2009). HPA Axis differences due to genotype will manifest initially in CRH concentrations, affecting the hypothalamic pituitary adrenal stress response (HPA axis). This effect translates peripherally in the form of plasma ACTH concentrations and subsequently in concentrations of plasma cortisol. 180 rhesus monkey subjects reared either with their mothers or in adult-absent, peer-only groups were genotyped and underwent a series of social separations from their attachment source. Blood samples were obtained one and two hours following separation to assay for ACTH and cortisol. Our analyses showed a significant effect of the orthologous CRH-248 genotype on plasma ACTH concentrations following repeated experimentally induced stress. Further analyses showed that this genotypic difference was only found however in the peer-reared subjects. Interestingly, analyses showed no effect of genotype on plasma cortisol levels. This finding suggests while negative feedback at the level of CRH is disrupted leading to pituitary hypersecretion of ACTH, intact negative feedback at the level of the adrenal cortex may moderate this dysfunction. Additionally, genotypic effects were only different after prolonged, chronic stress, as measured separations three and four. We suggest a GxE effect with CRH genotype effects only present after deleterious rearing experiences and chronic or repeated stressful situations.