Chronic stress, physiological adaptation and developmental programming of the neuroendocrine stress system

Chronic stress undermines physical and mental health, in part via dysregulation of the neuroendocrine stress system. Key to understand this dysregulation is recognizing that the problem is not stress per se, but rather its chronicity. The optimally functioning stress system is highly dynamic, and negative feedback regulation enforces transient responses to acute stressors. Chronic stress overrides this, and adaptation to the chronicity can result in persistent dysregulation by altering sensitivity thresholds critical for control of system dynamics. Such adaptation involves plasticity within the central nervous system (CNS) as well as epigenetic regulation. When it occurs during development, it can have persistent effects on neuroendocrine regulation. Understanding how chronic stress programs development of the neuroendocrine stress system requires elucidation of stress-responsive gene regulatory networks that control CNS plasticity and development.