Consequences of maternal abuse on HPA axis function, growth, and social and stress-induced behavior in juvenile rhesus macaques

Abstract

Common outcomes associated with childhood maltreatment are aggression, anxiety, depression, alterations in the HPA stress response system, and growth alterations. This study utilized an animal model to examine the long term behavioral and physiological effects of maternal maltreatment. Subjects were 10 rhesus macaques (Macaca mulatta) that were maternally abused during the first 3 months of life and 10 non-maternally abused subjects. HPA axis activity was examined at 24, 30, and 36 months of age. Blood draws were collected at morning, noon, and night to investigate basal levels and the diurnal rhythm of cortisol. The dexamethasone suppression test was administered to examine negative feedback of cortisol, and the ACTH and CRF challenges tests were used to determine pituitary and adrenal sensitivity. HPA stress responses and behavioral responses to stressors were investigated through the use of 3 separate laboratory paradigms (neutral object test, fear-evoking object test, and human intruder paradigm) that exposed the subjects to stimuli of varying threatening intensities. To investigate growth alterations, physical growth measurements and blood samples for growth hormone analyses were collected when subjects were 36, 42, and 48 months of age. Subjects were also observed in their social groups to investigate aggression and affiliative behavior. The results demonstrated that abused and control subjects differed in their behavioral responses to novel stimuli. Abused subjects explored and inspected novel objects more, inspected objects more quickly, avoided objects less, and were more likely to bite objects than control subjects. When subjects were exposed to a novel human making direct eye contact (highly threatening), abused subjects displayed more nervous behavior than controls. In the social group, abused subjects were more aggressive, but did not differ from controls with regard to the proportion of time spent in proximity or contact with group members. Contrary to hypotheses, abused subjects did not demonstrate HPA alterations, specifically HPA hypo-functionality. There was also no evidence that abused subjects had long term deficits in growth or growth processes. Future work will continue to investigate behavior and physiology into adulthood and attempt to identify biological mechanisms that may underlie the behavioral changes seen in abused subjects.