The role of early life stress in programming the HPA axis has been well-studied in animal models. Exposure to mild or moderate stressors early in life has been shown to enhance HPA regulation and promote a lifelong resilience to stress. In contrast, early-life exposure to extreme or prolonged stress can induce a hyper-reactive HPA axis and may contribute to lifelong vulnerability to stress. In one widely replicated experiment, rats subjected to the moderate stress of frequent human handling during the first two weeks of life had reduced hormonal and behavioral HPA-mediated stress responses as adults, whereas rats subjected to the extreme stress of prolonged periods of maternal separation showed heightened physiological and behavioral stress responses as adults.
