Prolonged Psychosocial Stress Research Articles

Prolonged psychosocial stress does not increase intestinal permeability compared to sham-stress in healthy females

Prolonged psychosocial stress does not increase intestinal permeability compared to sham-stress in healthy females

COVID-19-related distress is associated with analogue PTSD symptoms after exposure to an analogue stressor

ABSTRACT Background: The COVID-19 outbreak in early 2020 was associated with an immediate increase in mental health problems in a significant percentage of the general population. Therefore, it is crucial to investigate how the COVID-19 pandemic – as a psychosocial stressor – affected the aetiological processes of mental disorders. Previous research has shown that stress potentiates associative (fear) learning and analogue symptoms of posttraumatic stress disorder (PTSD) and that analogue PTSD symptoms can emerge in response to associative learning. Objective: We investigated whether distress in response to the COVID-19 outbreak support the development of intrusions and rumination after exposure to a non-COVID-19-related analogue trauma. Moreover, we examined if these effects are mediated by the strength of associative learning during analogue trauma. Method: 122 undergraduate university students participated in an online experiment between March and July 2020. They completed questionnaires measuring distress and rumination related to the COVID-19 outbreak. On a subsequent day, they went through an associative learning task, in which neutral stimuli were paired with the appearance of a highly aversive film clip. Subjective ratings were assessed as indicators of associative learning. On the next day, participants documented film-related intrusions and rumination. Results: COVID-19-related distress but not rumination was associated with post-film intrusion and rumination load. These effects were mediated by associative learning. Conclusions: The current findings are in line with the assumptions that stress enhanced both associative learning and PTSD symptoms. Specifically, they indicate that prolonged psychosocial stress – like during the COVID-19 outbreak – is linked to individual differences in memory processing of aversive events. Further confirmatory research is needed to replicate these results.

The Leuven prolonged acute stress test: a novel stress test that induces prolonged psychosocial stress in healthy females

The Leuven prolonged acute stress test: a novel stress test that induces prolonged psychosocial stress in healthy females

Chapter 6 - The hypothalamo–pituitary–adrenal axis and the autonomic nervous system in burnout

Burnout constitutes a serious health concern in the modern working environment. It is a stress-related condition that has developed as a result of a prolonged psychosocial stress exposure causing a persistent mismatch between demands and resources. The main symptom is emotional exhaustion, but physical fatigue, diminished professional efficacy, cynicism, and cognitive impairments are also associated with this condition. Burnout has been used both as a psychologic term in occupational settings and as a clinical diagnosis in patient populations, and there is currently no universally accepted definition and diagnostic criteria of burnout. It has been hypothesized that the two main stress response systems, the autonomic nervous system (ANS) and the hypothalamus-pituitary-adrenal axis (HPA axis), are involved in the pathogenesis of burnout. A common hypothesis is that in the early stages of chronic stress, the HPA axis and sympathetic ANS activity tend to be higher, while it will decrease with a longer duration of chronic stress to ultimately reach a state of hypoactivity in clinical burnout. The current research in this field shows many contradictory results. Thus there is no compelling evidence of either ANS or HPA dysfunction in burnout. However, there is partial support for the hypothesis of HPA and sympathetic hyperactivity in early stages, and HPA hyporeactivity and low vagal activity in more severe burnout cases, but high-quality studies investigating the causal links are still lacking.

Kososan, a Kampo medicine, prevents a social avoidance behavior and attenuates neuroinflammation in socially defeated mice

BackgroundKososan, a Kampo (traditional Japanese herbal) medicine, has been used for the therapy of depressive mood in humans. However, evidence for the antidepressant efficacy of kososan and potential mechanisms are lacking. Recently, it has been recognized that stress triggers neuroinflammation and suppresses adult neurogenesis, leading to depression and anxiety. Here, we examined whether kososan extract affected social behavior in mice exposed to chronic social defeat stress (CSDS), an animal model of prolonged psychosocial stress, and neuroinflammation induced by CSDS.MethodsIn the CSDS paradigm, C57BL/6J mice were exposed to 10 min of social defeat stress from an aggressive CD-1 mouse for 10 consecutive days (days 1–10). Kososan extract (1.0 g/kg) was administered orally once daily for 12 days (days 1–12). On day 11, the social avoidance test was performed to examine depressive- and anxious-like behaviors. To characterize the impacts of kososan on neuroinflammation and adult neurogenesis, immunochemical analyses and ex vivo microglial stimulation assay with lipopolysaccharide (LPS) were performed on days 13–15.ResultsOral administration of kososan extract alleviated social avoidance, depression- and anxiety-like behaviors, caused by CSDS exposure. CSDS exposure resulted in neuroinflammation, as indicated by the increased accumulation of microglia, the resident immune cells of the brain, and their activation in the hippocampus, which was reversed to normal levels by treatment with kososan extract. Additionally, in ex vivo studies, CSDS exposure potentiated the microglial pro-inflammatory response to a subsequent LPS challenge, an effect that was also blunted by kososan extract treatment. Indeed, the modulatory effect of kososan extract on neuroinflammation appears to be due to a hippocampal increase in an anti-inflammatory phenotype of microglia while sparing an increased pro-inflammatory phenotype of microglia caused by CSDS. Moreover, reduced adult hippocampal neurogenesis in defeated mice was recovered by kososan extract treatment.ConclusionsOur findings suggest that kososan extract prevents a social avoidant behavior in socially defeated mice that is partially mediated by the downregulation of hippocampal neuroinflammation, presumably by the relative increased anti-inflammatory microglia and regulation of adult hippocampal neurogenesis. Our present study also provides novel evidence for the beneficial effects of kososan on depression/anxiety and the possible underlying mechanisms.

Impact of radioactive contamination in East-Ural region: Socioecological assessments

Based on sociological surveys carried out by the Institute of Economics of the Ural Branch of Russian Academy of Sciences in 1992–2014 for cities, towns, and settlements in Chelyabinsk, Sverdlovsk, and Kurgan oblasts, an analysis has been conducted of radiation risks and their impact on the level of social and psychological tension at the territories of radioactive contamination in the Southern Urals. The degree of negative influence of radiophobia on social, labor, and cultural activity of inhabitants has been shown, as well as on their domestic and reproductive activity. A special aspect of the problem under consideration is the social and valeological wellbeing of the population groups that suffered from cataclysms of radiation accidents. Under the influence of long-term negative social and valeological memory, a large part of the population living in contaminated territories has special psychological status characterized by a rather high level of social and psychological tension, prolonged psychosocial stress, prepotency of accentuated personality features, and pathopsychological reactions and types of psychical response. Not excluding the possibility of recurrence of radiation accidents in the future in the areas with now-operating nuclear plants, the author suggests that adequate long-term rehabilitative measures oriented both to reducing the social and valeological risks of compulsory living and refining the activities and psychological comfort of the population in various manifestations are necessary.

Perceived stress at work is associated with lower levels of DHEA-S.

BackgroundIt is known that long-term psychosocial stress may cause or contribute to different diseases and symptoms and accelerate aging. One of the consequences of prolonged psychosocial stress may be a negative effect on the levels of dehydroepiandrosterone (DHEA) and its sulphated metabolite dehydroepiandrosterone sulphate (DHEA-S). The aim of this study is to investigate whether levels of DHEA and DHEA-S differ in individuals who report perceived stress at work compared to individuals who report no perceived stress at work.MethodsMorning fasting DHEA-S and DHEA levels were measured in serum in a non-stressed group (n = 40) and a stressed group (n = 41). DHEA and DHEA-S levels were compared between the groups using ANCOVA, controlling for age.ResultsThe mean DHEA-S levels were 23% lower in the subjects who reported stress at work compared to the non-stressed group. Statistical analysis (ANCOVA) showed a significant difference in DHEA-S levels between the groups (p = 0.010). There was no difference in DHEA level between the groups.ConclusionsThis study indicates that stressed individual have markedly lower levels of DHEA-S. Given the important and beneficial functions of DHEA and DHEA-S, lower levels of DHEA-S may constitute one link between psychosocial stress, ill health and accelerated ageing.

Perceived stress at work is associated with attenuated DHEA-S response during acute psychosocial stress

Dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEA-S) have been suggested to play a protective role during acute psychosocial stress, because they act as antagonists to the effects of the stress hormone cortisol. This study aims to investigate whether prolonged psychosocial stress, measured as perceived stress at work during the past week, is related to the capacity to produce DHEA and DHEA-S during acute psychosocial stress. It also aims to investigate whether prolonged perceived stress affects the balance between production of cortisol and DHEA-S during acute psychosocial stress. Thirty-six healthy subjects (19 men and 17 women, mean age 37 years, SD 5 years), were included. Perceived stress at work during the past week was measured by using the Stress-Energy (SE) Questionnaire. The participants were divided into three groups based on their mean scores; Low stress, Medium stress and High stress. The participants underwent the Trier Social Stress Test (TSST) and blood samples were collected before, directly after the stress test, and after 30 min of recovery. General Linear Models were used to investigate if the Medium stress group and the High stress group differ regarding stress response compared to the Low stress group. Higher perceived stress at work was associated with attenuated DHEA-S response during acute psychosocial stress. Furthermore, the ratio between the cortisol production and the DHEA-S production during the acute stress test were higher in individuals reporting higher perceived stress at work compared to individuals reporting low perceived stress at work. There was no statistical difference in DHEA response between the groups. This study shows that prolonged stress, measured as perceived stress at work during the past week, seems to negatively affect the capacity to produce DHEA-S during acute stress. Given the protective functions of DHEA-S, attenuated DHEA-S production during acute stress may lead to higher risk for adverse effects on psychological and physiological health, particularly if stress exposure continues.

Ghrelin mediates stress-induced food-reward behavior in mice

The popular media and personal anecdotes are rich with examples of stress-induced eating of calorically dense "comfort foods." Such behavioral reactions likely contribute to the increased prevalence of obesity in humans experiencing chronic stress or atypical depression. However, the molecular substrates and neurocircuits controlling the complex behaviors responsible for stress-based eating remain mostly unknown, and few animal models have been described for probing the mechanisms orchestrating this response. Here, we describe a system in which food-reward behavior, assessed using a conditioned place preference (CPP) task, is monitored in mice after exposure to chronic social defeat stress (CSDS), a model of prolonged psychosocial stress, featuring aspects of major depression and posttraumatic stress disorder. Under this regime, CSDS increased both CPP for and intake of high-fat diet, and stress-induced food-reward behavior was dependent on signaling by the peptide hormone ghrelin. Also, signaling specifically in catecholaminergic neurons mediated not only ghrelin's orexigenic, antidepressant-like, and food-reward behavioral effects, but also was sufficient to mediate stress-induced food-reward behavior. Thus, this mouse model has allowed us to ascribe a role for ghrelin-engaged catecholaminergic neurons in stress-induced eating.

Monocyte chemotactic protein-1 (MCP-1) and growth factors called into question as markers of prolonged psychosocial stress.

BackgroundPsychosocial stress is becoming a major contributor to increased mental ill-health and sick leave in many countries. Valid markers of chronic stress would be valuable for diagnostic and prognostic purposes. A recent study suggested monocyte chemotactic protein-1 (MCP-1), epidermal growth factor (EGF) and vascular endothelial growth factor (VEGF) as markers of chronic stress. We aimed to confirm these potential biomarkers of prolonged psychosocial stress in female patients.Methodology/Principal FindingsCirculating levels of MCP-1, EGF and VEGF, along with several other cytokines, were measured in plasma from 42 female patients suffering from exhaustion due to prolonged psychosocial stress and 42 control subjects, using a protein biochip immunoassay. There were no significant differences between patients and controls in any of the cytokines or growth factors analyzed. Furthermore, when using a different protein bioassay and reanalyzing MCP-1 and VEGF in the same samples, markedly different levels were obtained. To further explore if inflammation is present in patients with exhaustion, the classical inflammatory marker C-reactive protein (CRP) was measured in another group of patients (n = 89) and controls (n = 88) showing a small but significant increase of CRP levels in the patients.Conclusions/SignificanceMCP-1, EGF and VEGF may not be suitable markers of prolonged psychosocial stress as previously suggested. Furthermore, significant differences were obtained when using two different protein assays measuring the same samples, indicating that comparing studies where different analytic techniques have been used might be difficult. Increased levels of CRP indicate that low-grade inflammation might be present in patients with exhaustion due to prolonged stress exposure but this inflammation does not seem to be reflected by increase in circulating MCP-1 or other cytokines measured.

Novel Biochemical Markers of Psychosocial Stress in Women

BackgroundProlonged psychosocial stress is a condition assessed through self-reports. Here we aimed to identify biochemical markers for screening and early intervention in women.MethodsPlasma concentrations of interleukin (IL) 1-α, IL1-β, IL-2, IL-4, IL-6, IL-8, IL-10, interferon-γ (INF-γ), tumor necrosis factor-α (TNF-α), monocyte chemotactic protein-1 (MCP-1), epidermal growth factor (EGF), vascular endothelial growth factor (VEGF), thyroid stimulating hormone (TSH), total tri-iodothyronine (TT3), total thyroxine (TT4), prolactin, and testosterone were measured in: 195 women on long-term sick-leave for a stress-related affective disorder, 45 women at risk for professional burnout, and 84 healthy women.ResultsWe found significantly increased levels of MCP-1, VEGF and EGF in women exposed to prolonged psychosocial stress. Statistical analysis indicates that they independently associate with a significant risk for being classified as ill.ConclusionsMCP-1, EGF, and VEGF are potential markers for screening and early intervention in women under prolonged psychosocial stress.

Sex, stress and the hippocampus: allostasis, allostatic load and the aging process.

The adaptive responses of the body that maintain homeostasis in response to stressors can be called "allostasis", meaning "achieving stability through change". Mediators produced by the immune system, autonomic nervous system (ANS) and hypothalamo-pituitary-adrenal(HPA) axis produce allostasis. The brain also shows allostasis, involving the activation of nerve cell activity and the release of neurotransmitters. When the individual is challenged repeatedly or when the allostatic systems remain turned on when no longer needed, the mediators of allostasis can produce a wear and tear on the body and brain that has been termed "allostatic load". Examples of allostatic load include the accumulation of abdominal fat, the loss of bone minerals and the atrophy of nerve cells in the hippocampus. Studies of the hippocampus as a target of stress and sex hormones have revealed a considerable degree of structural plasticity and remodeling in the adult brain that differs between the sexes. Three forms of hippocampal structural plasticity are affected by circulating hormones: (1) repeated stress causes remodeling of dendrites in the CA3 region; (2) different modalities of stress suppress neurogenesis of dentate gyrus granule neurons; (3) ovarian steroids regulate synapse formation during the estrous cycle of female rats. All three forms of structural remodeling of the hippocampus are mediated by hormones working in concert with excitatory amino acids (EAA) and NMDA receptors. EAA and NMDA receptors are also involved in neuronal death that is caused in pyramidal neurons by seizures, by ischemia and by severe and prolonged psychosocial stress. The aging brain seems to be more vulnerable to such effects, although there are considerable individual differences in vulnerability that can be developmentally determined. Moreover, the brain retains considerable resilience in the face of stress, and estrogens appear to play a role in this resilience. "Resilience is an example of successful allostasis in which wear and tear is minimized, and estrogens exemplify the type of agent that works against the allostatic load associated with aging." This review discusses the current status of work on underlying mechanisms for protection and damage.

Stress, sex, hippocampal plasticity: relevance to psychiatric disorders

Studies of the hippocampus as a target of stress and sex hormones have revealed a considerable degree of structural plasticity and remodeling in the adult brain that differs between the sexes. These sex differences, as well as stress sensitivity, may be programmed by events early in life, including the developmental actions of gonadal, thyroid and adrenal hormones. Two forms of hippocampal structural plasticity are affected by stress. First, repeated stress causes remodeling of dendrites in the CA3 region. Second, different modalities of stress suppress neurogenesis of dentate gyrus granule neurons. In addition, ovarian steroids regulate synapse formation during the estrous cycle of female rats. All three forms of structural remodeling of the hippocampus are mediated by hormones working in concert with excitatory amino acids (EAA) and NMDA receptors. EAA and NMDA receptors are also involved in neuronal death that is caused in pyramidal neurons by seizures and ischemia, and by severe and prolonged psychosocial stress. Clinical MRI studies have shown that there is atrophy of the hippocampus in a number of psychiatric disorders, as well as during aging in some individuals, accompanied by deficits in declarative, episodic, spatial and contextual memory performance. It is, therefore, important to appreciate how hippocampal dysfunction may play a role in the symptoms of the psychiatric illness and, from a therapeutic standpoint, to distinguish between a permanent loss of cells and a reversible atrophy in order to develop treatment strategies to either prevent or reverse deficits. In addition, remodeling of neural tissue may occur in other brain regions, such as the amygdala and prefrontal cortex.

Stress and hippocampal plasticity: implications for the pathophysiology of affective disorders.

The hippocampal formation, a structure involved in declarative, spatial and contextual memory, is a particularly sensitive and vulnerable brain region to stress and stress hormones. The hippocampus shows a considerable degree of structural plasticity in the adult brain. Stress suppresses neurogenesis of dentate gyrus granule neurons, and repeated stress causes atrophy of dendrites in the CA3 region. In addition, ovarian steroids regulate synapse formation during the estrous cycle of female rats. All three forms of structural remodeling of the hippocampus are mediated by hormones working in concert with excitatory amino acids (EAA) and N-methyl-D-aspartate (NMDA) receptors. EAA and NMDA receptors are also involved in neuronal death that is caused in pyramidal neurons by seizures and by ischemia and prolonged psychosocial stress. In the human hippocampus, magnetic resonance imaging studies have shown that there is a selective atrophy in recurrent depressive illness, accompanied by deficits in memory performance. Hippocampal atrophy may be a feature of affective disorders that is not treated by all medications. From a therapeutic standpoint, it is essential to distinguish between permanent damage and reversible atrophy in order to develop treatment strategies to either prevent or reverse deficits. In addition, remodeling of brain cells may occur in other brain regions. Possible treatments are discussed. Copyright 2001 John Wiley & Sons, Ltd.

Exposure to chronic psychosocial stress and corticosterone in the rat: effects on spatial discrimination learning and hippocampal protein kinase Cgamma immunoreactivity.

Previous reports have demonstrated a striking increase of the immunoreactivity of the gamma-isoform of protein kinase C (PKCgamma-ir) in Ammon's horn and dentate gyrus (DG) of rodent hippocampus after training in a spatial orientation task. In the present study, we investigated how 8 days of psychosocial stress affects spatial discrimination learning in a hole board and influences PKCgamma-ir in the hippocampal formation. The acquisition of both reference memory and working memory was significantly delayed in the stressed animals during the entire training period. With respect to cellular plasticity, the training experience in both nonstressed and stressed groups yielded enhanced PKCgamma-ir in the CA1 and CA3 regions of the posterior hippocampus but not in subfields of the anterior hippocampus. Stress enhanced PKCgamma-ir in the DG and CA3 pyramidal cells of the anterior hippocampus. In stressed animals that were subsequently trained, the PKCgamma-ir was increased in the posterior CA1 region to the same level as that found in nonstressed trained animals. Stress apparently abrogated the PKCgamma-ir training response in the CA3 region. In a second experiment, the elevation of plasma corticosterone levels to values that are found during stress did not significantly influence reference memory scores but slightly and temporarily affected working memory. The training-induced enhancement of PKCgamma-ir in the CA1 region was similar in trained and corticosterone-treated trained animals, but the learning-induced PKCgamma-ir response in the posterior CA3 area was absent after corticosterone pretreatment. These results reveal that prolonged psychosocial stress causes spatial learning deficits, whereas artificial elevation of corticosterone levels to the levels that occur during stress only mildly affects spatial memory performance. The spatial learning deficits following stress are reflected only in part in the redistribution of hippocampal PKCgamma-ir following training.

Dynamics of central nervous 5-HT1A-receptors under psychosocial stress

It is well established that stress leads to changes in the serotonergic system. In order to gain a better understanding of the effects of recurrent stressful experiences on the serotonergic system, changes in the 5-HT1A-receptor system resulting from different periods of psychosocial stress (PSS) were analyzed in the present study. Male tree shrews (Tupaia belangeri) were submitted to subordination stress for 2, 10, 21, and 28 d. 5-HT1A-receptor binding was quantified by in vitro receptor autoradiography using the agonist 3H-8-OH-DPAT (3H-8-hydroxy-2-(di-n-propylamino)tetralin. PSS caused a downregulation of 3H-8-OH-DPAT binding sites in cortical areas and in the hippocampus. After 10, 21, and 28 d of PSS, the number of binding sites was reduced in layers V and VI of the posterior cingulate cortex (by 34%). After 28 d of PSS, the number of binding sites was reduced in the parietal cortex (by 18%), in the prefrontal cortex (by 16%), in the regio retrobulbaris (by 8%), and in region CA1 of the hippocampus (by 11%). In the raphe nuclei, no PSS-induced downregulation of 5-HT1A-receptors occurred. A transient increase in 3H-8-OH-DPAT binding was observed in the claustrum after 2 d of PSS (by 15%). There were also transient decreases in affinities for the radioligand probably representing receptor desensitization, for example, in the dorsal raphe nucleus after 28 d of PSS. In conclusion, the dynamic 5-HT1A-receptor changes occurring during PSS include downregulation and transient desensitization of receptors. They reflect regulatory mechanisms which probably lead to destabilization of the serotonergic system during prolonged PSS.

Chronic psychosocial stress induces morphological alterations in hippocampal pyramidal neurons of the tree shrew

The effect of sustained psychosocial stress on the morphology of hippocampal pyramidal neurons was analysed in male tree shrews after 14, 20, and 28 days of social confrontation. A variety of physiological changes such as constantly elevated levels of urinary cortisol and norepinephrine and reduced body weight, which are indicative of chronic stress were observed in the subordinate, but not in the dominant males. Light microscopic analysis of Nissl-stained hippocampal sections showed that the staining intensity of the nucleoplasm in the CA1 and CA3 pyramidal neurons was increased after prolonged psychosocial stress, indicating a change in the nuclear chromatin structure. These alterations were observed only in subordinate animals and increased in a time dependent manner in accordance with the length of the stress period. There was, however, neither a reduction in density nor a degeneration of pyramidal neurons in chronically stressed animals. Mechanisms which may possibly account for the observed alterations are discussed.