Neuroendocrine and Immunological Correlates of Chronic Stress in ‘Strictly Healthy’ Populations

Abstract

Background: Chronic stress has been associated with detrimental or maladaptive neuroendocrine and immunological changes. Objectives: We assessed the neuroendocrine and immunological correlates of a realistic chronic stress experienced by strictly healthy caregivers of Alzheimer’s disease patients and age-matched controls. Methods: We screened 330 caregivers and 206 non-caregivers according to the ‘strictly healthy’ conditions established by the SENIEUR protocol. Forty-one strictly healthy caregivers (60.56 ± 16.56 years) and 33 non-stressed controls (60.27 ± 14.11 years) were selected for this study. Salivary cortisol and dehydroepiandrosterone sulfate (DHEAS) were assessed at multiple points by radioimmunoassay. Peripheral T cell proliferation and cellular sensitivity to glucocorticoids (corticosterone and dexamethasone, DEX) were evaluated by colorimetric assays. We also examined the hypothalamic-pituitary-adrenal (HPA) axis response to the administration of a low-dose DEX in vivo. Results: The caregivers were significantly more stressed, anxious and depressed than non-caregivers (all p < 0.0001), in contrast to similar cortisol levels. Caregivers had reduced DHEAS levels (–32%, p < 0.0001), an increased cortisol/DHEAS ratio (39.7%, p < 0.0001) and impaired HPA axis response to DEX intake. Caregivers had a higher T cell proliferation (p < 0.0001) and increased sensitivity to glucocorticoids in vitro (p < 0.01) as compared to non-stressed controls. Conclusions: Our results suggest that the maintenance of health in chronically stressed populations may be associated with both protective and detrimental neuroendocrine and immunological changes.

Neurosteroid, GABAergic and hypothalamic pituitary adrenal (HPA) axis regulation: what is the current state of knowledge in humans?

“…However, compared with pre-stressor concentrations, basal cortisol averaged over awakening, 30 min after awakening, and at bedtime significantly increased during the first and second week of the teaching practice, while DHEA concentrations significantly decreased. These findings are generally in agreement with other human studies of chronic stress, which have shown that DHEA and DHEA-S concentrations tend to decline with chronic or repeated stress, while cortisol levels tend to rise or remain unchanged, resulting in elevated cortisol to DHEA and/or DHEA-S ratios (Jeckel et al 2010; Lennartsson et al 2013; Wolkowitz et al 2001). …”

“…However, the majority of studies suggest reduced basal levels of DHEA or DHEA-S in association with chronic psychosocial stress (Bellingrath et al 2009; Izawa et al 2012; Jeckel et al 2010; Lennartsson et al 2013; Vedhara et al 2002), though elevated levels have also been found (Lac et al 2012; Mommersteeg et al 2007). Because DHEA is a multifunctional steroid capable of a broad range of biological effects (Lac et al 2012; Maninger et al 2009; Oberbeck and Kobbe 2010), methodological differences within and across studies likely contribute to the heterogeneity of findings.…”

The Relationship between Dehydroepiandrosterone (DHEA), Working Memory and Distraction – A Behavioral and Electrophysiological Approach

“…On the other hand, stressful stimuli also modulate DHEA and DHEAS levels: acute stress is related to an increase in DHEA and DHEAS levels [20], [21], [22], [23] whereas chronic stress decreases baseline DHEA and DHEAS levels [24], [25], [26], [27], [28], as well as the acute DHEAS response to a superimposed psychological stress [29]. Yet, a direct influence of cognitive processing on DHEA or DHEAS levels has not been studied.…”

Care Transitions and Adult Day Services Moderate the Longitudinal Links between Stress Biomarkers and Family Caregivers' Functional Health

“…Chronically stressed populations such as dementia caregivers typically have reduced DHEA-s levels than non-stressed controls [36]. As an antagonist to cortisol, existing research generally suggests that lower DHEA-s levels were associated with greater health risks such as cardiovascular disease and all-cause mortality [2,37].…”