Chronic psychosocial stress results in sensitization of the HPA axis to acute heterotypic stressors despite a reduction of adrenal in vitro ACTH responsiveness

Chronic psychosocial stress is a risk factor for the development of numerous disorders, of which most are associated with chronic low-grade inflammation. Given the immunosuppressive effects of glucocorticoids (GC), one underlying mechanism might be the development of stress-induced GC resistance in certain immune cell subpopulations. In line with this hypothesis, male mice exposed to the chronic subordinate colony housing (CSC, 19 days) model develop GC resistance of in vitro lipopolysaccharide (LPS)-stimulated splenocytes, splenomegaly and an increased percentage of splenic CD11b+ cells. Here male C57BL/6N mice were euthanized at different days during CSC, and following 30 days of single housing after stressor termination to assess when CSC-induced splenic GC resistance starts to develop and whether this is a transient effect. Moreover, splenic CD11b, GC receptor (GR) and/or macrophage migration inhibiting factor (MIF) protein levels were quantified at respective days. While mild forms of CSC-induced GC resistance, increased splenic CD11b expression and/or splenomegaly were detectable on days 8 and 9 of CSC, more severe forms took until days 15 and 16 to develop, but normalized almost completely within 30 days following stressor termination (day 51). In contrast, splenic GR expression was decreased in CSC versus single-housed control (SHC) mice at all days assessed. While MIF expression was increased on days 15 and 16 of CSC, it was decreased in CSC versus SHC mice on day 20 despite persisting splenomegaly, increased CD11b expression and functional GC resistance. In summary, our data indicate that GC resistance and CD11b+ cell-mediated splenomegaly develop gradually and in parallel over time during CSC exposure and are transient in nature. Moreover, while we can exclude that CSC-induced reduction in splenic GR expression is sufficient to induce functional GC resistance, the role of MIF in CD11b+ cell-mediated splenomegaly and GC resistance requires further investigation.

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Stress Resilience: A Low-Anxiety Genotype Protects Male Mice From the Consequences of Chronic Psychosocial Stress

Endocrinology ◽

10.1210/en.2013-1742 ◽

2014 ◽

Vol 155 (1) ◽

pp. 117-126 ◽

Cited By ~ 25

Author(s):

Andrea M. Füchsl ◽

Inga D. Neumann ◽

Stefan O. Reber

Keyword(s):

Genetic Predisposition ◽

Psychosocial Stress ◽

Maternal Separation ◽

Plasma Corticosterone ◽

Interferon Γ ◽

Stress Effects ◽

Anxiogenic Effect ◽

Lymph Node Cells ◽

Chronic Psychosocial Stress

Chronic psychosocial stress is a risk factor for the development of affective as well as somatic disorders. However, vulnerability to adverse stress effects varies between individuals, with previous negative life events along with genetic predisposition playing a major role. In support, we previously showed that the consequences of chronic psychosocial stress induced by chronic subordinate colony housing (CSC, 19 days) can be amplified by pre-exposing mice to repeated maternal separation during early life. To test the significance of the genetic predisposition on the effects of CSC, mice selectively bred for high (mHAB) and low (mLAB) anxiety-related behavior and nonselected CD1 mice (mNAB) were exposed to CSC in the present study. In confirmation of our previous results, CSC mice of both mHAB and mNAB lines displayed chronic stress-related symptoms including increased adrenal weight, decreased adrenal in vitro ACTH sensitivity, lower plasma corticosterone to ACTH ratio, and increased interferon-γ secretion from isolated mesenteric lymph node cells compared with single-housed controls of the respective line. However, the CSC-induced anxiogenic effect found in mNAB was not confirmed in mHAB mice, possibly due to a ceiling effect in these highly anxious mice. Interestingly, mHAB were not more vulnerable to CSC than mNAB mice, whereas mLAB mice were resilient to CSC as indicated by all of the above mentioned parameters assessed. Taken together, our findings indicate that the genetic predisposition, in this case the innate anxiety of an individual, affects vulnerability to chronic psychosocial stress, with a low-anxiety phenotype mediating resilience to both affective and somatic consequences of CSC.

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HPA axis responses to psychosocial stress in patients with social phobia

Experimental and Clinical Endocrinology & Diabetes ◽

10.1055/s-0028-1096344 ◽

2008 ◽

Vol 116 (09) ◽

Author(s):

E Klumbies ◽

J Hoyer ◽

K Pöhlmann ◽

P Joraschky ◽

C Kirschbaum

Keyword(s):

Social Phobia ◽

Hpa Axis ◽

Psychosocial Stress

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A 16-week aerobic exercise and mindfulness-based intervention on chronic psychosocial stress: a pilot and feasibility study

Pilot and Feasibility Studies ◽

10.1186/s40814-020-00751-6 ◽

2021 ◽

Vol 7 (1) ◽

Author(s):

Guy A. Prochilo ◽

Ricardo J.S. Costa ◽

Craig Hassed ◽

Richard Chambers ◽

Pascal Molenberghs

Keyword(s):

Emotion Regulation ◽

Exercise Training ◽

Aerobic Exercise ◽

Psychosocial Stress ◽

Retention Rate ◽

Recruitment Rate ◽

Trial Registration ◽

Aerobic Exercise Training ◽

Definitive Trial ◽

Chronic Psychosocial Stress

Abstract Objectives Researchers have begun delivering mindfulness and aerobic exercise training concurrently on the premise that a combination intervention will yield salutary outcomes over and above each intervention alone. An estimate of the effect of combination training on chronic psychosocial stress in a nonclinical population has not been established. The objective of this study was to establish protocol feasibility in preparation of a definitive RCT targeting healthy individuals, and to explore the preliminary effect of combination training on reducing chronic psychosocial stress in this population. Methods Twenty-four participants were allocated to a single-arm pre-post study and subjected to 16 weeks of concurrent mindfulness psychoeducation and aerobic exercise training. Feasibility criteria were collected and evaluated. Within-group changes in chronic psychosocial stress, mindfulness, emotion regulation, and cardiorespiratory fitness were also assessed. Primary analyses were based on 17 participants. Results Retention rate, response rate, recruitment rate, and sample size analyses indicate a definitive trial is feasible for detecting most effects with precision. There was also a decline in our primary dependent measure of chronic psychosocial stress (dpretest = −0.56, 95% CI [ −1.14,−0.06]). With regard to secondary measures, there was an increase in the use of cognitive reappraisal, and a reduction in use of maladaptive emotion regulation strategies. We are insufficiently confident to comment on changes in mindfulness and aerobic capacity $\left (\dot {V}O_{2max}\right)$ V ̇ O 2 max . However, there were subgroup improvements in aerobic economy at submaximal exercise intensities. Conclusions We recommend a definitive trial is feasible and should proceed. Trial registration ANZCTR (ID: ACTRN12619001726145). Retrospectively registered December 9, 2019.

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Age-dependent susceptibility of adult hippocampal cell proliferation to chronic psychosocial stress

Brain Research ◽

10.1016/j.brainres.2005.05.006 ◽

2005 ◽

Vol 1049 (2) ◽

pp. 244-248 ◽

Cited By ~ 66

Author(s):

Mária Simon ◽

Boldizsár Czéh ◽

Eberhard Fuchs

Keyword(s):

Cell Proliferation ◽

Psychosocial Stress ◽

Hippocampal Cell ◽

Age Dependent ◽

Chronic Psychosocial Stress

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Glucocorticoid levels after exposure to predator odor and chronic psychosocial stress with dexamethasone application in rats

The Kaohsiung Journal of Medical Sciences ◽

10.1016/j.kjms.2016.04.011 ◽

2016 ◽

Vol 32 (5) ◽

pp. 235-240

Author(s):

Ana Starcevic ◽

Sasa Petricevic ◽

Zoran Radojicic ◽

Vuk Djulejic ◽

Andrej Ilankovic ◽

...

Keyword(s):

Psychosocial Stress ◽

Predator Odor ◽

Chronic Psychosocial Stress

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Chronic Psychosocial Stress in Mice Is Associated With Increased Acid Sphingomyelinase Activity in Liver and Serum and With Hepatic C16:0-Ceramide Accumulation

Frontiers in Psychiatry ◽

10.3389/fpsyt.2018.00496 ◽

2018 ◽

Vol 9 ◽

Cited By ~ 5

Author(s):

Martin Reichel ◽

Cosima Rhein ◽

Lena M. Hofmann ◽

Juliana Monti ◽

Lukasz Japtok ◽

...

Keyword(s):

Psychosocial Stress ◽

Acid Sphingomyelinase ◽

Chronic Psychosocial Stress ◽

Ceramide Accumulation

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An initial exploration of in vivo hair cortisol responses to a brief pain stressor: latency, localization and independence effects

Physiological Research ◽

10.33549/physiolres.931544 ◽

2009 ◽

pp. 757-761

Author(s):

CF Sharpley ◽

KG Kauter ◽

JR McFarlane

Keyword(s):

Hpa Axis ◽

Cold Pressor Test ◽

Cold Pressor ◽

Hair Follicles ◽

Repeated Measurements ◽

Single Observation ◽

Target Organs ◽

Cortisol Responses

Cortisol is secreted by the central hypothalamo-pituitary-adrenal axis and affects many target organs and tissues, particularly in response to stressor demands and infection. Recent data reporting cortisol synthesis in hair follicles have shown the existence of a parallel “peripheral” HPA-axis. However, although there is evidence from in vitro studies and single-observation comparisons between groups that cortisol from hair follicles reflects endocrine changes associated with stressor demands, there are no reports to date of repeated measurements of in vivo cortisol responsivity in hair to transitory stressors. This issue was investigated with three males who underwent 1 min cold pressor test (CP). Cortisol response in hair to stressor demand appears to be (a) swift but transitory, (b) localized to the site of the demand and (c) independent of central HPA-axis activity.

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