Abstract # 1956 Event # 132:

Scheduled for Friday, August 18, 2006 05:10 PM-05:30 PM: Session 13 (Regency East #1) Oral Presentation

Early Adverse Experience Alters Hypothalamic-Pituitary-Adrenal (HPA) Function of Rhesus Macaques: Effects of Serotonin Transporter Gene Variation and Sex.

M. M. Sanchez1,2, T. K. Newman3, J. D. Higley3, P. M. Plotsky1, C. B. Nemeroff1 and J. T. Winslow4
1Dept. of Psychiatry & Behavioral Sciences, Emory University, Atlanta, USA, 2Yerkes National Primate Research Center, Emory University, 3Laboratories of Clinical Studies nad Neurogenetics, NIAAA/NIH, 4IRP Neurobiology Primate Core, NIMH/NIH
     Early adversity/stress are risk factors for psychopathology and physiopathology. However, even under the most traumatic experiences some individuals are more vulnerable than others. Functional polymorphisms in the promoter region of the serotonin transporter gene (rh5-HTTLPR) have been associated with variations in emotional reactivity and HPA axis function, which are also modulated by early experiences. We have investigated the effects of repeated maternal separation (from 3-6 months of age) on emotional behavior and HPA axis function of rhesus monkeys (Macaca mulatta). Twenty six maternally-separated (MS) and twenty four matched control macaques have been studied longitudinally. All analyses were run using RM-ANOVA’s and the accepted level of significance was p<.05. Repeated maternal separation sensitized the infants’ HPA axis responses to stress, particularly in females and infants with the short rh5-HTTLPR allele. As juveniles, MS subjects exhibited enhanced startle reactivity, flattened cortisol diurnal rhythms and alterations in pituitary-adrenal function detected with CRF and ACTH pharmacological challenges. Most of these alterations suggest that the early adverse experience caused hyperactivity of CRF systems and HPA axis, followed by a subsequent compensatory downregulation at different levels. The negative outcomes were strongly affected by sex and serotonin transporter gene variation. Although the interactions between these factors are complex, females and subjects with the short allele were more vulnerable to the effects of maternal separations. [Support: MH58922, MH01005, MH57704 & RR00165].