Long-term Psychosocial Stress Research Articles

Epigenome-wide association study of long-term psychosocial stress in older adults

ABSTRACT Long-term psychosocial stress is strongly associated with negative physical and mental health outcomes, as well as adverse health behaviours; however, little is known about the role that stress plays on the epigenome. One proposed mechanism by which stress affects DNA methylation is through health behaviours. We conducted an epigenome-wide association study (EWAS) of cumulative psychosocial stress (n = 2,689) from the Health and Retirement Study (mean age = 70.4 years), assessing DNA methylation (Illumina Infinium HumanMethylationEPIC Beadchip) at 789,656 CpG sites. For identified CpG sites, we conducted a formal mediation analysis to examine whether smoking, alcohol use, physical activity, and body mass index (BMI) mediate the relationship between stress and DNA methylation. Nine CpG sites were associated with psychosocial stress (all p < 9E–07; FDR q < 0.10). Additionally, health behaviours and/or BMI mediated 9.4% to 21.8% of the relationship between stress and methylation at eight of the nine CpGs. Several of the identified CpGs were in or near genes associated with cardiometabolic traits, psychosocial disorders, inflammation, and smoking. These findings support our hypothesis that psychosocial stress is associated with DNA methylation across the epigenome. Furthermore, specific health behaviours mediate only a modest percentage of this relationship, providing evidence that other mechanisms may link stress and DNA methylation.

Transnational families, care and wellbeing: The role of legal status and sibling relationships across borders

With transnational mobility on the rise, care is today increasingly carried out across borders, which profoundly impacts the wellbeing of migrants and their families. Drawing on two in-depth qualitative studies with Brazilian migrants in the United States, this article extends discussions on transnational care circulation by exploring two understudied dimensions in transnational care arrangements: legal status and sibling relationships. These two dimensions highlight the importance of legal (undocumented) status and larger family networks, besides the traditional aging parent-adult child dyad, in transnational care practices, family cohesion and wellbeing. The article's findings are two-fold. First, it shows that undocumented siblings experience long-term psychosocial stress resulting from the legal impossibility of their return visits and to make up for that, they provide emotional forms of care from a distance. Second, it reveals a gendered and sexualized component to care provision within family and sibling relationships, wherein women and gay siblings are typically expected, almost as a ‘naturalized’ role, to take on care responsibilities. This is the case regardless of being a migrant or non-migrant, documented or undocumented sibling.

Unobtrusive Continuous Stress Detection in Knowledge Work—Statistical Analysis on User Acceptance

Modern knowledge work is highly intense and demanding, exposing workers to long-term psychosocial stress. In order to address the problem, stress detection technologies have been developed, enabling the continuous assessment of personal stress based on multimodal sensor data. However, stakeholders lack insights into how employees perceive different monitoring technologies and whether they are willing to share stress-indicative data in order to sustain well-being at the individual, team, and organizational levels in the knowledge work context. To fill this research gap, we developed a theoretical model for knowledge workers’ interest in sharing their stress-indicative data collected with unobtrusive sensors and examined it empirically using structural equation modeling (SEM) with a survey of 181 European knowledge workers. The results did not show statistically significant privacy concerns regarding environmental sensors such as air quality, sound level, and motion sensors. On the other hand, concerns about more privacy-sensitive methods such as tracking personal device usage patterns did not prevent user acceptance nor intent to share data. Overall, knowledge workers were highly interested in employing stress monitoring technologies to measure their stress levels and receive information about their personal well-being. The results validate the willingness to accept the unobtrusive, continuous stress detection in the context of knowledge work.

Психосоциальный стресс перенаселенности (скученности): негативные последствия для организма человека и грызунов

The paper provides an overview of literature and our own data on the negative consequences of psychosocial stress induced by overpopulation for humans. It also explores the effect of crowding on rodents (rats and mice) in a vivarium as an experimental model of overpopulation. Experimental studies on rodents (the existing and our own research) focus on the influence of crowding on the general state of the body, the development of stress reactions, the content of monoamines and their metabolites in the brain, the state of the immune system, e. g., cytokine profile and interferon status. It was concluded that long-term crowding in rodents (mainly rats) in a vivarium is a huge stress factor. It has a negative impact on the general state of the body, leads to anxiety / depressive disorders, interferes with the hypothalamic-pituitary-adrenal system, creates an imbalance of monoamines and their metabolites in a number of brain structures, and compromises the immunity. In our own experiments, we used the model of crowding to test the effect of stress induced by a confined space: after a month in standard vivarium conditions (four to six individuals in a cage), a group of male rats was placed in crowded conditions (from fifteen to seventeen individuals in a cage) for 2 weeks. It is assumed that the model may be used for preclinical assessment of anxiolytic, antidepressant, immunomodulatory and other properties of various biologically active substances and drugs used in fighting the negative consequences of long-term psychosocial stress.

The "Managed" or Damaged Heart? Emotional Labor, Gender, and Posttraumatic Stressors Predict Workplace Event-Related Acute Changes in Cortisol, Oxytocin, and Heart Rate Variability.

Vital to the everyday operation of police services, police communicators (911 call-takers and dispatchers) are persistently subject to imminent challenges in the workplace; they must always be prepared to engage and deal with a wide variety of circumstances that provoke various intense emotions and physiological stress responses. Acute changes in cortisol, oxytocin, and heart rate variability are central to adaptive responses in stressful complex social interactions, but they might also be indicative of physiological dysregulation due to long-term psychosocial stress exposures. Thus, we examine acute stress-induced release of peripheral oxytocin and cortisol along with changes in heart rate variability, and how each relates to persistent workplace stressors and symptoms of posttraumatic stress. Findings indicate chronic forms of gendered workplace stress such as emotional labor, gender role stress and, posttraumatic stress each have differential associations with, and predict physiological responses to, acutely stressful events in the workplace. These associations suggest potential mechanisms through which communicators become more vulnerable to developing stress-related disorders such as posttraumatic stress injuries, especially after cumulative traumatic exposures in this context. The results also suggest potential pathways for the biological embedding of stressful gendered workplace experiences.

Association of Hair Cortisol Concentration with Prevalence of Major Cardiovascular Risk Factors and Allostatic Load.

BackgroundThe high prevalence of cardiovascular diseases cannot be explained completely by conventional risk factors such as older age, smoking, diabetes mellitus, hypertension, obesity, and dyslipidemia. Results of recent studies indicate that chronic stress may be an independent risk factor for cardiovascular morbidity and mortality. Thus, the aim of our study was to investigate the associations between the hair cortisol concentration (HCC), which is considered as a potential biomarker of long-term psychosocial stress, and traditional cardiovascular risk factors, including smoking, dyslipidemia, hypertension, and obesity.Material/MethodsFasting blood samples and anthropometric and lifestyle data were collected from 163 apparently healthy men. HCC was determined using high-performance liquid chromatography. Allostatic load (AL) index, defined as an integrated score of multiple interacting systems involved in the adaptation to adverse physical or psychosocial situations, was also calculated.ResultsWe found that many prevalent cardiovascular risk factors, including hypertension, smoking, higher than recommended waist circumference (WC), and low-density lipoprotein cholesterol (LDL-C) median values, are associated with higher HCC. Hair cortisol level was also positively associated with the manifestation of individual cardiovascular risk factors such as higher-than-recommended total cholesterol, LDL-C, non-high-density lipoprotein cholesterol, body mass index, and WC median values. Moreover, a significant positive relationship between HCC and AL index was observed.ConclusionsThe results of this study suggest that increased prevalence of traditional cardiovascular risk factors is associated with higher HCC. Also, both HCC and AL index might be appropriate markers for the evaluation of chronic stress level.

Gene expression signature in brain regions exposed to long-term psychosocial stress following acute challenge with cannabinoid drugs

Repeated exposure to life stressors can overwhelm the body’s capacity to restore homeostasis and result in severe negative consequences. Cannabinoid CB1 receptors are highly expressed in the Central Nervous System (CNS) and regulate both glucocorticoid signalling and neurotransmitter release. In rodents, WIN55212.2 is a full agonist at the cannabinoid receptor type-1, while Rimonabant is a potent and selective cannabinoid inverse agonist at this receptor. This study aims to investigate the effect of long-term psychosocial stress following acute challenge with cannabinoid drugs on gene expression in distinct brain regions; this is done by employing digital multiplexed gene expression analysis.We found that repeated stress increased cortical mRNA levels of dopamine receptor D2, while the expression of neuregulin-1 decreased in both the prefrontal cortex and cerebellum. Further, we found that the acute injection of the agonist WIN55212.2 reduced striatal levels of dopamine receptor D2, while the use of inverse agonist Rimonabant acted in the opposite direction. The analysis of the interaction between the drugs and repeated stress revealed that defeat mice treated with WIN55212.2 showed lower expression of a set of myelin-related genes, as did the expression of SRY-box 10 and dopamine receptors-D1 and -D2 in the prefrontal cortex when compared to vehicle. In addition, in the hippocampus of stressed mice treated with WIN55212.2, we found an elevated expression of oligodendrocyte transcription factor-1, -2 and zinc finger protein 488 when compared to vehicle. In comparison to vehicle, an increase in 2′,3′-Cyclic nucleotide 3′-phosphodiesterase and oligodendrocyte transcription factor-1 occurred in the cerebellum of stressed animals treated with the agonist. Moreover, treatment with Rimonabant under the influence of stress induced an overexpression of a set of myelin-related genes in the prefrontal cortex when compared to WIN-treated animals.In conclusion, repeated stress interfered with the dopaminergic system in the prefrontal cortex. We demonstrated that the expression of dopamine receptor D2 in the striatum was mediated by the CB1 receptor. Stressed mice exposed to either WIN55212.2 or Rimonabant displayed pronounced deficits in CNS myelination. In addition, the pharmacological blockage of CB1 receptor in stressed mice deregulated the expression of dopamine receptors and might lead to dysfunctions in dopamine metabolism.

Low Levels of Dehydroepiandrosterone Sulfate in Younger Burnout Patients.

ObjectiveDehydroepiandrosterone sulphate (DHEA-s) is an anabolic protective hormone of importance for maintenance of health. DHEA-s levels peak in young adults and decline thereafter with age. DHEA-s has previously been shown to be lower in individuals reporting prolonged stress. This study investigates DHEA-s levels in patients with clinical burnout, a disorder caused by long-term psychosocial stress.Methods122 patients (51% men) and 47 controls (51% men) in the age 25–54 years were included in the study. DHEA-s levels were compared between patients and controls in the whole sample and within each of the three 10-year-interval age groups.ResultsIn the youngest age group (25–34 years), DHEA-s levels were on average 25% lower in the patients (p = 0.006). The differences in DHEA-s levels between patients and controls were more pronounced among female than male participants (on average 32% and 13% lower, respectively). There were no differences in DHEA-s levels between patients and controls in the age group 35–44 years (p = 0.927) or 45–54 years (p = 0.897) or when analyzing all age groups together (p = 0.187).ConclusionThe study indicates that levels of the health promoting “youth” hormone DHEA-s are low in younger burnout patients. The fact that younger adults have much higher DHEA-s levels and more pronounced inter-subject variability in DHEA-s levels than older individuals might explain why burnout status differentiates patients from controls only among the youngest patients included in this study.

Burnout and Hypocortisolism - A Matter of Severity? A Study on ACTH and Cortisol Responses to Acute Psychosocial Stress.

Background: Common consequences of long-term psychosocial stress are fatigue and burnout. It has been suggested that burnout could be associated with hypocortisolism, thus, inability to produce sufficient amounts of cortisol. This study aimed to investigate whether patients with clinical burnout exhibit aberrant ACTH and cortisol responses under acute psychosocial stress compared with healthy individuals.Methods: Nineteen patients (9 men and 10 women) and 37 healthy subjects (20 men and 17 women), underwent the Trier Social Stress Test. Blood samples and saliva samples were collected before, after, and during the stress test for measurements of plasma ACTH, serum cortisol, and salivary cortisol. Several statistical analyses were conducted to compare the responses between patients and controls. In addition, in order to investigate the possibility that burnout patients with more severe symptoms would respond differently, sub-groups of patients reporting higher and lower burnout scores were compared.Results: In both patients and healthy controls, we observed elevated levels of ACTH and cortisol after exposure to the stressor. There were no differences in responses of ACTH, serum cortisol, or salivary cortisol between patients and controls. Patients reporting higher burnout scores had lower salivary cortisol responses than controls, indicating that patients with more severe burnout symptoms may be suffering from hypocortisolism. In addition, patients with more severe burnout symptoms tended to have smaller ACTH responses than the other patients. However, there was no corresponding difference in serum cortisol.Conclusion: This study indicates that hypocortisolism is not present in a clinical burnout patient group as a whole but may be present in the patients with more severe burnout symptoms.

Burnout is associated with elevated prolactin levels in men but not in women

ObjectiveProlactin levels have been shown to be increased by different types of psychosocial stress. Since burnout is a consequence of long-term psychosocial stress, prolactin levels might also be affected in burnout. The aim of this study was to investigate whether there are differences in prolactin levels between individuals who report burnout and others. MethodMorning fasting serum prolactin levels were compared between individuals who reported burnout (24 men and 25 women) and individuals who reported no burnout (25 men and 13 women). Women were tested in the follicular phase of the menstrual cycle. Men and women were analysed separately. ResultsMen who reported burnout exhibited significantly higher (34%) serum prolactin levels compared to men who reported no burnout. The prolactin levels in women who reported burnout were not different from the levels in the women who reported no burnout before or after adjusting for estradiol levels. ConclusionsThis study indicates that prolactin levels are higher in men with burnout than men without burnout but not affected in women with burnout. Why no association was seen in women needs to be further explored.

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.

Unemployment and ill health: a connection through inflammation?

BackgroundUnemployment is a source of acute and long-term psychosocial stress. Acute and chronic psychosocial stress can induce pronounced changes in human immune responses. In this study we tested our hypothesis that stress-induced low-grade tissue inflammation is more prevalent among the unemployed.MethodsWe determined the inflammatory status of 225 general population subjects below the general retirement age (65 years in Finland). Those who had levels of both interleukin-6 (≥ 0.97 pg/mL) and high-sensitivity C-reactive protein (≥ 1.49 mg/L) above the median were assessed to have an elevated inflammatory status (n = 72).ResultsAn elevated inflammatory status was more common among the unemployed than among other study participants (59% versus 30%, p = 0.011). In the final multivariate model, those who were unemployed had over five-fold greater odds for having an elevated inflammatory status (OR 5.20, 95% CI 1.55-17.43, p = 0.008).ConclusionThis preliminary finding suggests that stress-induced low-grade inflammation might be a link between unemployment and ill health.

Astroglial Plasticity in the Hippocampus is Affected by Chronic Psychosocial Stress and Concomitant Fluoxetine Treatment

Analysis of post-mortem tissue from patients with affective disorders has revealed a decreased number of glial cells in several brain areas. Here, we examined whether long-term psychosocial stress influences the number and morphology of hippocampal astrocytes in an animal model with high validity for research on the pathophysiology of major depression. Adult male tree shrews were submitted to 5 weeks of psychosocial stress, after which immunocytochemical and quantitative stereological techniques were used to estimate the total number and somal volume of glial fibrillary acidic protein-positive astrocytes in the hippocampal formation. Stress significantly decreased both the number (-25%) and somal volume (-25%) of astroglia, effects that correlated notably with the stress-induced hippocampal volume reduction. Additionally, we examined whether antidepressant treatment with fluoxetine, a selective serotonin reuptake inhibitor, offered protection from these stress-induced effects. Animals were subjected to 7 days of psychosocial stress before the onset of daily oral administration of fluoxetine (15 mg/kg per day), with stress continued throughout the 28-day treatment period. Fluoxetine treatment prevented the stress-induced numerical decrease of astrocytes, but had no counteracting effect on somal volume shrinkage. In nonstressed animals, fluoxetine treatment had no effect on the number of astrocytes, but stress exposure significantly reduced their somal volumes (-20%). These notable changes of astroglial structural plasticity in response to stress and antidepressant treatment support the notion that glial changes may contribute to the pathophysiology of affective disorders as well as to the cellular actions of antidepressants.

Chronic stress decreases the number of parvalbumin-immunoreactive interneurons in the hippocampus: prevention by treatment with a substance P receptor (NK1) antagonist.

Previous studies have demonstrated that stress may affect the hippocampal GABAergic system. Here, we examined whether long-term psychosocial stress influenced the number of parvalbumin-containing GABAergic cells, known to provide the most powerful inhibitory input to the perisomatic region of principal cells. Adult male tree shrews were submitted to 5 weeks of stress, after which immunocytochemical and quantitative stereological techniques were used to estimate the total number of hippocampal parvalbumin-immunoreactive (PV-IR) neurons. Stress significantly decreased the number of PV-IR cells in the dentate gyrus (DG) (-33%), CA2 (-28%), and CA3 (-29%), whereas the CA1 was not affected. Additionally, we examined whether antidepressant treatment offered protection from this stress-induced effect. We administered fluoxetine (15 mg/kg per day) and SLV-323 (20 mg/kg per day), a novel neurokinin 1 receptor (NK1R) antagonist, because the NK1R has been proposed as a possible target for novel antidepressant therapies. Animals were subjected to a 7-day period of psychosocial stress before the onset of daily oral administration of the drugs, with stress continued throughout the 28-day treatment period. NK1R antagonist administration completely prevented the stress-induced reduction of the number of PV-IR interneurons, whereas fluoxetine attenuated this decrement in the DG, without affecting the CA2 and CA3. The effect of stress on interneuron numbers may reflect real cell loss; alternatively, parvalbumin concentration is diminished in the neurons, which might indicate a compensatory attempt. In either case, antidepressant treatment offered protection from the effect of stress and appears to modulate the hippocampal GABAergic system. Furthermore, the NK1R antagonist SLV-323 showed neurobiological efficacy similar to that of fluoxetine.

Social factors and life events as predictors for children's health. A one-year prospective study within a general practice.

During a period of one year information was obtained concerning social background, life events and diseases among children, who happened to consult the general practitioner. One year after this index consultation information concerning the children's present state of health was obtained. 43 (13%) had been admitted to hospital during the follow-up year. 45 (12%) had had more than 5 consultations at the general practitioner, and the parents of 23 children (6%) stated that their child had poor health. A multivariate predictor-analysis was performed. The associations discovered suggest 1) that the selected social or psycho-social factors do not appear to be of considerable importance for prediction of later hospitalization, 2) that indices for short-term psycho-social stress appear to increase the risk for many consultations at the general practitioner, 3) that "poor health" in the children is partly predicted by indices for more longterm psycho-social stress.