Consequences of Chronic Stress on the PINE Network

Abstract

Stress is a risk factor for the development and progression of a variety of disorders. At the same time stress is essential to initiate adaptation to the current situation and to promote survival of the fittest. Thus, responses to stress evolved to be fast and efficient. This is implemented by a tight networking of the psycho-immune-neuro-energy (PINE) system. Within the PINE network, glucocorticoids are the universal messengers that regulate overall physiology jointly with cytokines, neurotransmitters and energy status. While the secretion of glucocorticoids in response to stress is itself a rather unspecific reaction to any kind of stressor, complexity of the outcome is encoded by lifetime, recent and present events. Together, these individual experiences modulate the diurnal and ultradian rhythmicity of glucocorticoid levels. Given the time- and dose-dependency of glucocorticoid signaling, this rhythmicity allows for flexibility in the coping with stress. In a chronic stress setting, the interaction of PINE network components is altered. While stress-resilient individuals retain adaptive capacity, vulnerable individuals lose flexibility in their responsiveness. Gene × environment interactions could explain individual differences. To better elucidate the molecular underpinnings of risk and resiliency, models that allow studying the consequences of chronic stress on the PINE network are required.