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Review
. 2018 Oct;30(10):e12641.
doi: 10.1111/jne.12641. Epub 2018 Oct 7.

Factors promoting vulnerability to dysregulated stress reactivity and stress-related disease

Ashley L Russell  1   2 , Jeffrey G Tasker  3 , Aldo B Lucion  4 , Jenny Fiedler  5 , Carolina D Munhoz  6 , Tao-Yiao John Wu  1   2   7 , Terrence Deak  8
Affiliations
Review

Factors promoting vulnerability to dysregulated stress reactivity and stress-related disease

Ashley L Russell et al. J Neuroendocrinol. 2018 Oct.

Abstract

Effective coordination of the biological stress response is integral for the behavioural well-being of an organism. Stress reactivity is coordinated by an interplay of the neuroendocrine system and the sympathetic nervous system. The hypothalamic-pituitary-adrenal (HPA) axis plays a key role in orchestrating the bodily responses to stress, and the activity of the axis can be modified by a wide range of experiential events. This review focuses on several factors that influence subsequent HPA axis reactivity. Some of these factors include early-life adversity, exposure to chronic stress, immune activation and traumatic brain injury. The central premise is that each of these experiences serves as a general vulnerability factor that accelerates future HPA axis reactivity in ways that make individuals more sensitive to stress challenges, therefore feeding forward into the exacerbation of ongoing (or greater susceptibility toward) future stress-related disease states, especially as they pertain to negative affect and overall brain health.

Keywords: anxiety; depression; glucocorticoids; inflammation; oxytocin; stress; traumatic brain injury.

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Figures

Figure 1.
Figure 1.
Relative time courses of major components of the generalized stress response. Stress exposure stimulates excitatory input to the hypothalamus, which triggers a rapid activation of the sympathetic motor system, followed by a delayed activation of the HPA axis.
Figure 2.
Figure 2.
HPA axis. HPA axis activation consists of CRF release from the hypothalamus, which stimulates ACTH secretion from the anterior pituitary and corticosteroid secretion from the adrenal cortex. Glucocorticoids feedback at multiple levels of the HPA axis and limbic system.
Figure 3.
Figure 3.
Schematic summary of feed-forward influences of external threats on subsequent stress reactivity (TBI = traumatic brain injury, HPA = hypothalamus-pituitary-adrenal axis, SNS = sympathetic nervous system).
Figure 4.
Figure 4.
Glucocorticoid-induced suppression of synaptic excitation. Glucocorticoids stimulate the synthesis of the endocannabinoid 2-AG (eCB), which acts as a retrograde messenger to inhibit glutamate release from excitatory synapses via presynaptic CB1 receptor activation.
See this image and copyright information in PMC

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