Interactions between psychosocial stress and the circadian endogenous clock

Abstract

Animals are exposed to regular daily challenges in their environment as well as to unpredictable stressful events, so-called stressors. Both measures require adequate physiological responses that are controlled by the circadian system and the stress system. The two systems are highly linked with each other. The circadian system prepares the animal for the regular daily challenges by upregulating the stress system before the animal's activity phase every day. In addition, unpredicted environmental challenges upregulate the stress system independently of the circadian system. This can happen at any time, even in the middle of the animal's sleeping phase. Although the stress system feeds back on the brain, the circadian master clock in the suprachiasmatic nuclei (SCN) of the hypothalamus is usually not disturbed by stressful events, but instead continues to activate the animal in a regular daily manner. However, the stability of the SCN clock appears to fade away after chronic stress, in particular after chronic psychosocial stress. Chronic psychosocial stress is the major risk factor for major depression and certain anxiety disorders in humans and therefore deserves attention. Here, I review the interactions between the circadian and stress systems after chronic psychosocial stress in an animal model, the social defeat paradigm.

The HPA Axis under Stress and Aging: Individual Vulnerability is Associated with Behavioral Patterns and Exposure Time

“…GCs have a wide range of physiological effects, which range from regulation of carbohydrate, lipid, and protein metabolism and immune signaling [ 2,4,20,28,36,37 ] to effects on brain function, behavior, emotion, and cognition. [ 20,28,33,38 ] They influence most HPA axis functions associated with adaptation of the body to stress exposure. Another important effect of GCs is the provision of inhibitory feedback at the level of hypothalamic neuroendocrine neurons, adenohypophysial corticotrophs, as well as higher brain centers involved in the regulation of neuroendocrine neurons (hippocampus, amygdala, and prefrontal cortex).…”

“…Recently, an increasing number of both experimental and clinical reports have indicated a dependence on the time of day, not only of HPA axis activity under basal conditions, but also in reaction to stress exposure. [ 20–22,28,41 ] In general, the HPA axis is more sensitive to stress exposure at the end of the active phase of the day, or during the inactive phase when glucocorticoid levels are low, and less sensitive to stress effects in the active phase when basal glucocorticoid levels are high. [ 20–22,28 ] In both humans and laboratory primates, HPA axis function is more sensitive to stress late in the day than in morning hours.…”

“…[ 20–22,28,41 ] In general, the HPA axis is more sensitive to stress exposure at the end of the active phase of the day, or during the inactive phase when glucocorticoid levels are low, and less sensitive to stress effects in the active phase when basal glucocorticoid levels are high. [ 20–22,28 ] In both humans and laboratory primates, HPA axis function is more sensitive to stress late in the day than in morning hours. [ 20–22,28 ] For example, young (6–8 years old) female rhesus monkeys showed a much higher increase in ACTH and CORT levels in response to a 2 h moderate restraint stress (acute psycho‐emotional stress exposure, ASE) imposed at 15 h than to the same stress imposed at 9 h ( Figure 1 ).…”

“…[ 20–25 ] Disorders of circadian fluctuation of HPA axis function play an important role in specific aging‐related diseases, such as depression, anxiety, type 2 diabetes, cognitive and autoimmune disorders, as well as contributing to accelerated aging. [ 2,23,25–28 ] Therefore, investigations of the individual characteristics of age‐related changes in HPA axis function that include consideration of circadian modulation of HPA axis functioning are extremely important. Biomarkers are needed both to identify individuals with increased vulnerability to stress and age‐related pathologies and for understanding the mechanisms of individual differences.…”

Chronobiological research for cognitive science: A multifaceted view

“…Dysfunction of the circadian clock induced by shift work, for example, significantly increases the risk of developing metabolic syndromes (e.g., diabetes, stroke), cardiovascular diseases, or cancer. Furthermore, as highlighted by a review by Helfrich‐Förster () in this special collection, the circadian system interacts with the stress system such that not only stress responsiveness varies over the course of the day, but repeated psychosocial stress is also able to disturb the circadian clock.…”