The hypothalamic-pituitary-adrenal axis as a substrate for stress resilience: Interactions with the circadian clock

Stress, primarily processed via the hypothalamic-pituitary-adrenal (HPA) axis, engages biological pathways throughout the brain and body which promote adaptation and survival to changing environmental demands. Adaptation to environmental challenges is compromised when these pathways are no longer functioning optimally. The physiological and behavioral mechanisms through which HPA axis function influences stress adaptation and resilience are not fully elucidated. Our understanding of stress biology and disease must take into account the complex interactions between the endocrine system, neural circuits, and behavioral coping strategies. In addition, further consideration must be taken concerning influences of other aspects of physiology, including the circadian clock which is critical for regulation of daily changes in HPA activity. While adding a layer of complexity, it also offers targets for intervention. Understanding the role of HPA function in mediating these diverse biological responses will lead to important insights about how to bolster successful stress adaptation and promote stress resilience.