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

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.

Roles for androgens in mediating the sex differences of neuroendocrine and behavioral stress responses

“…Furthermore, T has been shown to attenuate cortisol release in men [100]. The androgenic suppression of hypothalamic-pituitary-adrenal (HPA) axis responses may play a key role in decreasing susceptibility to develop anxiety and depression, since chronic high levels of glucocorticoids are a key contributor to the development of these disorders [101].…”

Genetics of resilience: Implications from genome‐wide association studies and candidate genes of the stress response system in posttraumatic stress disorder and depression

“…The HPA axis is a major neuroendocrine system that affects various organ systems and plays a fundamental role in mediating stress response which is supported by the fact that disturbances in normal HPA function are associated with depressive and anxiety symptoms (Russell et al, ; Russo, Murrough, Han, Charney, & Nestler, ). With regard to the HPA axis, several genes and their potential impact on vulnerable phenotypes have been studied, but there are few studies that have investigated the link between genes of this hormone system and resilience.…”

Hippocampal subfield volumes are uniquely affected in PTSD and depression: International analysis of 31 cohorts from the PGC-ENIGMA PTSD Working Group

“…Our results extend prior work showing smaller volumes in the CA1 among individuals with C-PTSD and depression (36,43,44), and suggest that CA1 integrity is more vulnerable to the effects of depression than PTSD. CA1 volume differences may reflect stress-induced alterations in negative feedback projections from the hippocampus to the hypothalamus, which are principally supplied by the CA1 pyramidal cell (7,54). Excitatory input to the CA1 occurs at different layers; distal apical dendrite tufts receive glutamatergic signals from the entorhinal cortex (ERC) through the perforant pathway (ERC layerIII→CA1), whereas dendrites proximal to the soma receive glutamatergic signals from the amygdala and Schaffer collateral (ERC layerII→DG→CA2/3→CA1) (54,55).…”

“…PTSD has been linked to structural and functional brain changes via dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis -a negative feedback loop that promotes adaptive responses to actual or perceived threat (5,6). During acute stress, the hypothalamus rapidly activates the sympathetic nervous system to mobilize energy through the release of catecholamines (7,8). Subsequently, the HPA axis is activated and corticotropin-releasing hormone (CRH) is released from the hypothalamus into the hypophyseal portal circulation.…”