Early Rearing Experience, Hypothalamic-Pituitary-Adrenal (HPA) Activity, and Serotonin Transporter Genotype: Influences on the Development of Anxiety in Infant Rhesus Monkeys (Macaca mulatta)

A gene x environment interaction exists in the expression of anxiety for both human and nonhuman primates, such that individuals who are carriers of the (s) allele of the serotonin transporter genotype ( 5-HTT LPR) and exposed to early life stress are more at risk for exhibiting anxiety. The hypothalamic-pituitary-adrenal (HPA) axis has also been implicated in anxiety disorders but the relationship between early life/genotype, HPA activity, and anxiety is not well understood. Further, studies linking the HPA axis to anxiety have relied on point samples (blood and salivary cortisol) which reflect moments in time rather than long-term activity. The purpose of this dissertation was three fold: (1) to examine anxious behavior in monkeys with different 5-HTT LPR genotypes and rearing environments across the first two years of life, (2) to compare long-term HPA activity (as measured with hair cortisol) with acute HPA activity (as measured with salivary cortisol) in the same period, and (3) to determine which measure of HPA activity predicts anxiety and/or mediates the rearing/genotype influences on anxious behavior. Infant rhesus monkeys ( Macaca mulatta , N=61) were mother-peer-reared (MPR, n=21), peer-reared (PR, n=20), or surrogate-peer-reared (SPR, n=20) for 8 months, then all relocated into a large social housing situation for the next 18 months. Monkeys were genotyped for 5-HTT LPR and hair and saliva samples were collected for cortisol analysis at months 6, 12, 18, and 24. Behavior was recorded twice per week per subject from 2-24 months and analyzed for the duration of anxiety, social play, and grooming. Regression analysis established predictors of these behaviors. Rearing condition and sex were significant predictors of anxiety across the two years, and HPA activity added significant predictive power in the first six months only. Mediation of the rearing/anxiety relationship by the HPA axis was not evident. Interestingly, hair (but not salivary) cortisol early in life was positively correlated with later anxious behavior. These findings demonstrate the detrimental effects of adverse early life experience on behavioral development and shed light on the interplay between environment, adrenocortical activity, and anxiety. They further demonstrate the usefulness of a long-term measure of HPA activity in predicting later behavior