Chronic Psychosocial Stress Research Articles

Community Social Stressors and Susceptibility to Urban Air Pollution in Cardiovascular Disease

Cardiovascular disease (CVD), the leading cause of death in the U.S., has been linked to chronic and acute air pollution exposures. Research has identified stronger effects of air pollution in lower-socioeconomic position (SEP) communities, where pollution exposures are also often higher. While specific factors underlying this susceptibility are unknown, chronic psychosocial stress related to social adversity is hypothesized as a key component. In this study, we use data on 1.3 million New York City (NYC) CVD emergency department (ED) visits, multiple air pollutants [fine particles (PM2.5), nitrogen dioxide (NO2), sulfur dioxide (SO2)], and community-level SEP, violence, and race-based residential segregation to: (1) examine associations between spatiotemporal pollution exposures and CVD events in NYC for 2005-2011, and (2) assess effect modification in pollution-CVD associations by community social stressors. In case-crossover models examining associations between spatio-temporal air pollution and CVD, we found significant same-day associations between NO2 and risk of any CVD event, ischemic heart disease, and heart failure; this association remained significant with any form of co-pollutant adjustment. Significant associations for PM2.5 and SO2 on all CVD, heart failure (for PM2.5), and ischemic heart disease (for SO2) were somewhat less robust to co-pollutant adjustment. Finally, to test effect modification in the relationship between spatio-temporal pollution measures and CVD, we tested whether associations with individual-level CVD risk differed by community SEP and/ or chronic stressors. We found, as hypothesized, stronger associations between pollutants and CVD risk among individuals in communities with higher social stressor exposures. Further analyses are needed to compare relative modification by multiple community stressors.

Mediterranean diet, stress resilience, and aging in nonhuman primates

Persistent psychological stress increases the risk of many chronic diseases of aging. Little progress has been made to effectively reduce stress responses or mitigate stress effects suggesting a need for better understanding of factors that influence stress responses. Limited evidence suggests that diet may be a factor in modifying the effects of stress. However, long-term studies of diet effects on stress reactive systems are not available, and controlled randomized clinical trials are difficult and costly. Here we report the outcomes of a controlled, randomized preclinical trial of the effects of long-term consumption (31 months, ~ equivalent to 9 human years) of Western versus Mediterranean - like diets on behavioral and physiological responses to acute (brief social separation) and chronic (social subordination) psychosocial stress in 38 adult, socially-housed, female cynomolgus macaques. Compared to animals fed a Western diet, those fed the Mediterranean diet exhibited enhanced stress resilience as indicated by lower sympathetic activity, brisker and more overt heart rate responses to acute stress, more rapid recovery, and lower cortisol responses to acute psychological stress and adrenocorticotropin (ACTH) challenge. Furthermore, age-related increases in sympathetic activity and cortisol responses to stress were delayed by the Mediterranean diet. Population level diet modification in humans has been shown to be feasible. Our findings suggest that population-wide adoption of a Mediterranean-like diet pattern may provide a cost-effective intervention on psychological stress and promote healthy aging with the potential for widespread efficacy.

Effects chronic administration of corticosterone and estrogen on HPA axis activity and telomere length in brain areas of female rats

Chronic stress is related to the acceleration of telomere shortening. Recent work showed a correlation between chronic psychosocial stress and reduced telomere length in certain cells. The exposure of T lymphocytes to cortisol promoted a significant reduction in telomerase activity. Although stress can promote changes in telomere length, whether increased glucocorticoid concentrations alter telomere length in brain tissue cells is unclear. In addition to modulating the activity of the stress system, estrogen also influences telomere length. The objective of this study was to verify whether chronic exposure to glucocorticoids promotes changes in the telomere length of encephalic areas involved in the control of HPA axis activity and whether estrogen affects these changes. Wistar rats were ovariectomized and treated with estradiol cypionate [(50 or 100 μg/kg, subcutaneously)] or oil and 20 mg/kg corticosterone or vehicle (isotonic saline with 2% Tween 80, subcutaneously) for 28 days. On the day after the end of the hormonal treatment, the animals were euthanized for collection of blood, brain and pituitary gland samples. Estrogen modulated the activity of the HPA axis. CRH, AVP and POMC mRNA levels were reduced by estrogen. At least in doses and treatment time used, there was no correlation between effects of exposure to glucocorticoids and estrogen on telomere length in the brain areas of female rats. However, estrogen treatment reduced the telomere length in the central amygdala and dorsal hippocampus, but not in the PVN, indicating a variation of reaction of telomeres for estrogen in different brain areas.

Changes in adrenal functioning induced by chronic psychosocial stress in male mice: A time course study

Background and aim: Chronic subordinate colony housing (CSC, 19 days), an established and preclinically-validated mouse model for posttraumatic stress disorder (PTSD), causes evening hypocorticism and a reduced adrenal in vitro ACTH (adrenocorticotropic hormone) sensitivity despite pronounced adrenal hyperplasia. However, until now it remains unclear at what time point during CSC exposure evening hypocorticism and adrenal in vitro ACTH insensitivity develop and whether the repeated change of dominant aggressor mice plays an important role in this context. It is, therefore, the aim of the current study, to explore the detailed time course of these stress-induced adrenal changes. Methods: Adrenal weight, plasma corticosterone (CORT) and ACTH were assessed in the morning of days 8 (right before exposure to the 2nd aggressor), 9 (24 h after exposure to the 2nd aggressor), 15 (right before exposure to the 3rd aggressor), 16 (24 h after exposure to the 3rd aggressor) and 20 or in the evening of days 8 (10 h after exposure to the 2nd aggressor), 9 (34 h after exposure to the 2nd aggressor), 15 (10 h after exposure to the 3rd aggressor), 16 (34 h after exposure to the 3rd aggressor) and 20 of CSC exposure. Moreover, we in vitro cultured adrenal explants of all mice euthanized in the morning of days 8, 9, 15, 16 and 20 either in the presence or absence of ACTH to subsequently assess CORT concentration in the supernatants. Results: Our results indicate that while adrenal mass was increased at all time points assessed, plasma morning CORT only transiently increased in response to the 2nd (on day 8) but not 3rd (on day 15) dominant aggressor mouse. Moreover, although mild signs of adrenal in vitro ACTH insensitivity developed already after one week of CSC exposure, moderate and severe adrenal in vitro ACTH insensitivity required two and three weeks of chronic subordination, respectively. Conclusion: Together with unaffected plasma ACTH levels at all time points assessed, our data suggest that stress-induced adrenal in vitro ACTH insensitivity develops gradually during times of chronic subordination while subordination to different aggressor mice aggravates its severity. Moreover, a mild form of adrenal ACTH insensitivity seems to allow prevention of morning hypercorticism on day 8 of CSC, despite functional adrenal mass being increased, while a moderate and severe form of adrenal ACTH insensitivity in CSC mice seems to promote HPA axis adaptation to repeated homotypic stressor exposure (i.e. dominant aggressor mice) and basal evening hypocorticism in CSC mice, respectively. Our results might, therefore, be the basis for future clinical studies assessing CORT supplementation as novel treatment regimen for somatic and affective pathologies linked to chronic and/or traumatic stress.

Inducing a stressed phenotype in healthy recipient mice by adoptively transferring CD4+ lymphocytes from mice undergoing chronic psychosocial stress

Although chronic stress is an acknowledged risk factor for the development of somatic and affective disorders, the cellular and molecular mechanisms underlying stress-induced pathologies are not fully understood. Interestingly, rodent studies involving immune cell transfer suggest that CD4+ T cells might be at least in part involved in reactivation of a chemically-induced colitis by stress. However, until now evidence is lacking that these immune cell types are indeed involved in the development of a “stressed phenotype”.The aim of the present study was, therefore, to assess the effects of adoptively transferring total mesenteric lymph node cells (mesLNCs) and CD4+ mesLNCs isolated from chronically-stressed mice into healthy recipient mice on various physiological, immunological and behavioral parameters. To induce chronic psychosocial stress in donor mice we employed the chronic subordinate colony housing (CSC) paradigm.Our data indicate that transfer of total or CD4+ mesLNCs from CSC mice, compared with respective cells from single-housed control (SHC) mice, promoted splenomegaly and interferon (IFN)-γ secretion from in vitro anti-CD3-stimulated mesLNCs in naïve recipient mice. This effect was independent of recipient mice additionally being administered with dextran sulfate sodium (DSS) or not. Transfer of CD4+ mesLNCs additionally increased adrenal weight and secretion of IL-6 from in vitro anti-CD3 stimulated mesLNCs in recipients administered with DSS. Importantly, transfer of neither cell type from CSC vs. SHC donor mice affected anxiety-related behavior of recipient mice in the light-dark box.Taken together, our data demonstrate that typical physiological and immunological, but not behavioral, effects of chronic stress can be induced in naïve recipient mice by adoptively transferring mesLNCs, in particular CD4+ mesLNCs, from chronically stressed donor mice.

Behavioral and hormonal effects of prolonged Sildenafil treatment in a mouse model of chronic social stress

Chronic social defeat can inhibit the reproductive system of subordinate males and causes behavioral deficits. Sildenafil treatment increases mice testosterone levels through its effects on Leydig cells of mice and it has been found to work as an antidepressant drug both in humans and in animal models. Since previous findings showed that sildenafil can counteract the inhibitory effects of chronic social defeat on agonistic, reproductive and anxiety-like behaviors of subordinate male mice, we investigated whether these behavioral outcomes can be explained by Sildenafil stimulation of testosterone. CD1 mice underwent an intruder-resident paradigm. After the fifth day of test, subordinate mice were injected with either a 10 mg/kg Sildenafil or a saline solution for 4 weeks. The results of the present study showed that Sildenafil treatment increased counterattacking behaviors and sexual motivation of subordinate males in addition to limiting the increase in body weight often observed in subordinate mice following chronic psychosocial stress. Moreover, sildenafil treated mice showed a pattern of behaviors reflecting lower anxiety. In agreement with previous studies, Sildenafil also increased testosterone levels. These data demonstrate that sildenafil can counteract the effects of chronic stress, possibly through its stimulatory effects on Leydig cells. These data demonstrate that sildenafil might counteract the effects of chronic psychosocial stress through centrally and peripherally mediated mechanisms.

The role of the microbiome and psychosocial stress in the expression and activity of drug metabolizing enzymes in mice

The gut microbiota is involved in a number of different metabolic processes of the host organism, including the metabolism of xenobiotics. In our study, we focused on liver cytochromes P450 (CYPs), which can metabolize a wide range of exo- and endogenous molecules. We studied changes in mRNA expression and CYP enzyme activities, as well as the mRNA expression of transcription factors that have an important role in CYP expression, all in stressed germ-free (GF) and stressed specific-pathogen-free (SPF) mice. Besides the presence of the gut microbiota, we looked at the difference between acute and chronic stress. Our results show that stress has an impact on CYP mRNA expression, but it is mainly chronic stress that has a significant effect on enzyme activities along with the gut microbiome. In acutely stressed mice, we observed significant changes at the mRNA level, however, the corresponding enzyme activities were not influenced. Our study suggests an important role of the gut microbiota along with chronic psychosocial stress in the expression and activity of CYPs, which can potentially lead to less effective drug metabolism and, as a result, a harmful impact on the organism.

Neuroprotective effects of cerium oxide nanoparticles on experimental stress-induced depression in male rats

Introduction: Inflammation and oxidative/nitrative stress induced by chronic psychosocial or physical stress play fundamental roles in the pathogenesis of depression, and lead to the loss of neurotrophic support, decreased neurogenesis and synaptic plasticity in the hippocampus. Findings have shown inhibition of inflammation waterfall may offer new approaches to the treatment of depression, especially for patients with treatment-resistant depression (TRD). Cerium Oxide (CeO2) is the oxide form of cerium, a rare earth element in the lanthanide series. Cerium oxide nanoparticles (CeO2NPs) are potent regenerative antioxidant and anti-inflammatory agents. We evaluated the neuroprotective and the neuronal plasticity activities of CeO2NPs in the stress-induced model of depression. Methods: We have analyzed the effects of single-dose intrahippocampal and intracerebroventricular (ICV) injections of CeO2NPs treatment on immobility behavior (forced swimming test), hippocampal IL-6 and malondialdehyde (Elisa), cell survival (Nissl staining), dentate gyrus BrdU-positive cells (Immunohistofluorescence) and growth associated protein-43 (GAp-43) expression (Immunohistofluorescence) of the hippocampal CA3 region. Results: In our study, single-dose CeO2NPs treatment could effectively suppress inflammatory and oxidative markers level induced by unpredictable chronic mild stress (UCMS) and improved immobility behavior, increased hippocampal cell proliferation, cell survival and neurite outgrowth, and thereby, prevented the progression of hippocampal destruction and dysfunction. Conclusion: This study demonstrates a new prospect for the treatment of depression. Our study gives us the confidence to continue the investigation of CeO2 NPs as a novel therapy, especially, for TRD that characterized by chronic and persistent inflammation.

Abdominal surgery prior to chronic psychosocial stress promotes spleen cell (re)activity and glucocorticoid resistance

There is convincing evidence from different mouse models that chronic psychosocial stress promotes splenomegaly, basal and lipopolysaccharide (LPS)-induced in vitro splenocyte activation and insensitivity towards glucocorticoids (GC) in in vitro LPS-treated splenocytes. However, we just recently showed, employing the chronic subordinate colony housing (CSC) paradigm, that bite wounds received during stressor exposure drive these stress-induced spleen changes. As skin wounds induced by planned surgery or physical trauma are more adequately reflecting what chronically stressed humans are likely to experience, it was the objective of the present study to investigate whether abdominal surgery prior to stressor exposure also promotes respective stress-induced spleen effects in the absence of any bite wounds. In line with our hypothesis, abdominal surgery prior to CSC induced splenomegaly, increased in vitro cell viability under basal and LPS conditions as well as the delta response to LPS (LPS – basal), and promoted the inability of isolated splenocytes to respond with a decreased cell viability to increasing concentrations of corticosterone following LPS-stimulation in vitro. Together with previous data, these findings demonstrate that physical injury, either in form of received bite wounds during stressor exposure or in form of abdominal surgery prior to stressor exposure, promotes the development of splenic immune activation and GC resistance.

Exposure to Violence, Psychosocial Stress, and Asthma.

Over the last two decades, chronic psychosocial stress has been linked to asthma. Exposure to violence is a common stressor for people living in urban settings, particularly in the U.S, and has received increased attention in the asthma literature in recent years. Improving our understanding of whether and how exposure to chronic stressors causes or worsens asthma could help us gain insights into disease pathogenesis, design public health policies, and develop new therapies. In this review, we assess the evidence linking violence or stress to asthma, describe recent insights on potential mechanisms, and discuss challenges and future directions. To date, experimental and observational studies suggest a causal association between chronic stress and worse asthma control, and a growing body of literature suggests that pre- or post-natal chronic stress may lead to new-onset asthma. Such evidence supports conducting randomized controlled trials of stress-reduction interventions to improve asthma control in subjects with high chronic stress. On the other hand, additional studies are needed to better understand if the specific stressor of violence exposure leads to asthma or worse asthma outcomes. Longitudinal studies with assessment of co-exposures and coping mechanisms are key to not only better understand the independent effects of violence or stress on asthma but also to identify factors that could ameliorate or worsen such effects. At this time, preliminary evidence supports prospective studies of whether and how chronic stress affects asthma or treatment responses through changes in DNA methylation or gene expression in cells relevant to disease pathogenesis.

Termination of acute stress response by the endocannabinoid system is regulated through lysine-specific demethylase 1-mediated transcriptional repression of 2-AG hydrolases ABHD6 and MAGL.

Acute environmental stress rarely implies long-lasting neurophysiological and behavioral alterations. On the contrary, chronic stress exerts a potent toxic effect at the glutamatergic synapse whose altered physiology has been recognized as a core trait of neuropsychiatric disorders. The endocannabinoid system (ECS) plays an important role in the homeostatic response to acute stress. In particular, stress induces synthesis of endocannabinoid (eCB) 2-arachidonyl glycerol (2-AG). 2-AG stimulates presynaptic cannabinoid 1 (CB1) receptor contributing to stress response termination through inhibition of glutamate release, restraining thereafter anxiety arousal. We employ mouse models of stress response coupled to gene expression analyses, unravelling that in response to acute psychosocial stress in the mouse hippocampus, ECS-mediated synaptic modulation is enhanced via transcriptional repression of two enzymes involved in 2-AG degradation: α/β-hydrolase domain containing 6 (ABHD6) and monoacylglycerol lipase (MAGL). Such a process is orchestrated by the epigenetic corepressor LSD1 who directly interacts with promoter regulatory regions of Abhd6 and Magl. Remarkably, negative transcriptional control of Abhd6 and Magl is lost in the hippocampus upon chronic psychosocial stress, possibly contributing to trauma-induced drift of synapse physiology toward uncontrolled glutamate transmission. We previously showed that in mice lysine-specific demethylase 1 (LSD1) increases its hippocampal expression in response to psychosocial stress preventing excessive consolidation of anxiety-related plasticity. In this work, we unravel a nodal epigenetic modulation of eCB turn over, shedding new light on the molecular substrate of converging stress-terminating effects displayed by ECS and LSD1.

Down-regulation of miR-181a promotes microglial M1 polarization through increasing expression of NDRG2

Background: Microglia exist in two polarized states: a classical activation state (M1) and an alternative activation state (M2). Accumulating evidence has suggested an involvement of miR-181a in neuronal development, survival, function, and plasticity, but its exact functional role in microglial polarization still requires clarification. We investigated the impact of miR-181a on microglial polarization using a rat chronic social stress model of depression. Methods: N9 microglia were stimulated with lipopolysaccharide (LPS; 100 ng/mL ) or IL-4 (10 ng/mL ) for 12h. Expression of Nos2, Arg-1, miR-181a, and NDRG2 was determined using real-time PCR. NDRG2 and syntaxin-1A protein expressions were analyzed by western blotting. The cell viability of N2A neuron was measured by an MTT assay. Body weight gain and adrenal weight were also evaluated. Results: Five weeks of daily social defeat significantly increased Nos2 and NDRG2 mRNA expression and dramatically reduced miR-181a expression in the hippocampus. Microglia were also polarized into different functional phenotypes. LPS treatment significantly enhanced mRNA expression of Nos2 and dramatically inhibited the expression of miR-181a. Conversely, treatment with IL-4 markedly increased the mRNA levels of Arg-1 and the expression of miR-181a. Expression of miR-181a regulated microglia differentiation by targeting NDRG2, while inhibition of miR-181a expression in N9 microglia induced N2A neuron death, which could be reversed by NDRG2 interference. Overexpression of miR-181a overcame the impacts of chronic psychosocial stress on body weight gain, adrenal weight, and syntaxin-1A expression in the hippocampus. Conclusion: Down-regulation of miR-181a promoted microglial M1 polarization by enhancing NDRG2 expression. Keywords: miR-181a, microglial M1 polarization, NDRG2

Increased dipeptidyl peptidase-4 accelerates chronic stress-related thrombosis in a mouse carotid artery model.

Exposure to chronic psychosocial stress is a risk factor for metabolic cardiovascular disorders. Given that dipeptidyl peptidase-4 (DPP-4) has an important role in human pathobiology, we investigated the role of DPP-4 in stress-related thrombosis in mice, focusing on oxidative stress and the von Willebrand factor (vWF)-cleaving protease ADAMTS13 (a disintegrin and metalloproteinase with thrombospondin type 1 motif, member 13). Male mice randomly assigned to nonstress and 2-week immobilized-stress groups underwent iron chloride3 (FeCl3)-induced carotid artery thrombosis surgery for morphological and biochemical studies at specific times. On day 14 post-stress/surgery, stress had enhanced the lengths and weights of arterial thrombi, with alterations of plasma DPP-4, plasminogen activation inhibitor-1 and ADAMTS13. The stressed mice had increased levels of vascular cell adhesion molecule-1, intracellular adhesion molecule-1, monocyte chemoattractant protein-1, gp91phox, p22phox, matrix metalloproteinase-2 (MMP-2), MMP-9, cathepsins S and K mRNAs and/or proteins, and reduced levels of endothelial nitric oxide synthase, catalase and superoxide dismutase-1 mRNAs and/or proteins. Stress also accelerated arterial endothelial cell damage. The DPP-4 inhibitor anagliptin ameliorated the stress-induced targeted molecular and morphological changes and thrombosis. In vitro, DPP-4 inhibition also mitigated the alterations in the targeted ADAMTS13 and other oxidative and inflammatory molecules in human umbilical vein endothelial cells in response to H2O2. DPP-4 inhibition appeared to improve the FeCl3-induced thrombosis in mice that received stress, possibly via the improvement of ADAMTS13 and oxidative stress, suggesting that DPP-4 could become a novel therapeutic target for chronic psychological stress-related thrombotic events in metabolic cardiovascular disorders.

The daily grind: Assessing bruxism as a potential indicator of stress in archaeological human remains

The identification of stress indicators in archaeological human remains is confounded not only by how paleopathologists define “stress”, but also by our understanding of how stress impacts the body. With the interpretation of commonly used osteological stress indicators being cautioned, if not challenged, the door is open for bioarchaeologists to explore new ways of identifying stress in past populations. One potentially identifiable stress response is bruxism. A behavior disorder characterized by the unconscious grinding and/or clenching of teeth, bruxism is often associated with acute and chronic psychosocial stress. This disorder is quite common; international clinical literature shows the disorder affecting up to 31% of adults and 20% of children. Though the frequency and severity of bruxism varies by individual, the long-term pathological impact of bruxing can be severe. Bruxism is associated with excessive dental attrition, abfraction, fracture, hypercementosis, occlusal pits, myofascial pain, hypertrophy of masticatory muscles, and possibly with mandibular and maxillary tori and temporomandibular disorder (TMD). However, despite its prevalence, associated pathologies, and association with stress, bruxism is rarely discussed in the osteological “stress” literature. This lack of attention is likely due to the challenges inherent in differential diagnosis. Evidence of bruxism may be obscured, exacerbated, and/or confounded by masticatory wear, malocclusion, tooth-loss, and general aging. Furthermore, the idiosyncratic nature of the disorder and the variability in the biomechanical forces associated with it (clenching vs. grinding) suggest that the dental effects will present differently within and between individuals, which may further complicate diagnosis. Despite these obstacles, as a clinically-correlated stress response, bruxism is a potentially useful new avenue for conceptualizing and identifying stress in past populations.

Chronic Psychosocial Stress Causes Increased Anxiety-Like Behavior and Alters Endocannabinoid Levels in the Brain of C57Bl/6J Mice

Introduction: Chronic stress causes a variety of physiological and behavioral alterations, including social impairments, altered endocrine function, and an increased risk for psychiatric disorders. Thereby, social stress is one of the most effective stressful stimuli among mammals and considered to be one of the major risk factors for the onset and progression of neuropsychiatric diseases. For analyzing the effects of social stress in mice, the resident/intruder paradigm of social defeat is a widely used model. Although the chronic social defeat stress model has been extensively studied, little is known about the effects of repeated or chronic social defeat stress on the endocannabinoid system (ECS). The present study aimed to understand the effects of chronic social stress on anxiety behavior and the levels of endocannabinoids (ECs) and two N-acylethanolamines (NAEs) in different brain regions of mice. Materials and Methods: Two-month-old, male C57Bl/6J mice were exposed to chronic psychosocial stress for 3 weeks. The effects of stress on anxiety behavior were measured using the light-dark box and hole board test. The EC levels of 2-arachidonoyl glycerol (2-AG) and anandamide (N-arachidonoylethanolamine [AEA]), as well as the levels of two NAEs (oleoylethanolamide [OEA] and palmitoylethanolamide), were analyzed by liquid chromatography-tandem mass spectrometry in the hippocampus, cerebellum, and cortex. Results: In comparison with control mice (n=12), mice exposed to social defeat stress (n=11) showed increased anxiety behaviors in the light-dark box and hole board test and gained significantly more weight during the experimental period. Additionally, chronic social stress induced differential alterations in the brain levels of 2-AG and AEA. More precisely, 2-AG levels were higher in the cortex and cerebellum, whereas reduced AEA levels were found in the hippocampus. Furthermore, we observed lower OEA levels in the hippocampus. Conclusion: The current study confirms that the ECS plays an essential role in stress responses, whereby its modulation seems to be brain region dependent.

Effects of social subordination and oestradiol on resting-state amygdala functional connectivity in adult female rhesus monkeys.

Preclinical studies demonstrate that chronic stress modulates the effects of oestradiol (E2) on behaviour through the modification of the amygdala and the medial prefrontal cortex (mPFC) neuronal structure. Clinical studies suggest that alterations in amygdala functional connectivity (FC) with the mPFC may be associated with stress-related phenotypes, including mood and anxiety disorders. Thus, identifying the effects of stress and E2 on amygdala-mPFC circuits is critical for understanding the neurobiology underpinning the vulnerability to stress-related disorders in women. In the present study, we used a well-validated rhesus monkey model of chronic psychosocial stress (subordinate social rank) to examine effects of E2 on subordinate (SUB) (i.e. high stress) and dominant (DOM) (i.e. low stress) female resting-state amygdala FC with the mPFC and with the whole-brain. In the non-E2 treatment control condition, SUB was associated with stronger left amygdala FC to subgenual cingulate (Brodmann area [BA] 25: BA25), a region implicated in several psychopathologies in people. In SUB females, E2 treatment strengthened right amygdala-BA25 FC, induced a net positive amygdala-visual cortex FC that was positively associated with frequency of submissive behaviours, and weakened positive amygdala-para/hippocampus FC. Our findings show that subordinate social rank alters amygdala FC and the impact of E2 on amygdala FC with BA25 and with regions involved in visual processing and memory encoding.

Chronic, Elevated Maternal Corticosterone During Pregnancy in the Mouse Increases Allergic Airway Inflammation in Offspring.

Allergic asthma is a chronic pulmonary disorder fundamentally linked to immune dysfunction. Since the immune system begins developing in utero, prenatal exposures can affect immune programming and increase risk for diseases such as allergic asthma. Chronic psychosocial stress during pregnancy is one such risk factor, having been associated with increased risk for atopic diseases including allergic asthma in children. To begin to define the underlying causes of the association between maternal stress and allergic airway inflammation in offspring, we developed a mouse model of chronic heightened stress hormone during pregnancy. Continuous oral administration of corticosterone (CORT) to pregnant mice throughout the second half of pregnancy resulted in an ~2-fold increase in circulating hormone in dams with no concomitant increase in fetal circulation, similar to the human condition. To determine how prolonged heightened stress hormone affected allergic immunity in offspring, we induced allergic asthma with house dust mite (HDM) and examined the airway immune response to allergen. Female mice responded to HDM more frequently and had a more robust immune cell response compared to their male counterparts, irrespective of maternal treatment. Male offspring from CORT-treated dams had a greater number of inflammatory cells in the lung in response to HDM compared to males from control dams, while maternal treatment did not affect immune cell numbers in females. Alternatively, maternal CORT caused enhanced goblet cell hyperplasia in female offspring following HDM, an effect that was not observed in male offspring. In summary, prenatal exposure to mild, prolonged heightened stress hormone had sexually dimorphic effects on allergic inflammation in airways of adult offspring.

Chronic psychosocial stress during pregnancy affects maternal behavior and neuroendocrine function and modulates hypothalamic CRH and nuclear steroid receptor expression

Postpartum depression (PPD) affects up to 20% of mothers and has negative consequences for both mother and child. Although exposure to psychosocial stress during pregnancy and abnormalities in the hypothalamic pituitary adrenal (HPA) axis have been linked to PPD, molecular changes in the brain that contribute to this disease remain unknown. This study utilized a novel chronic psychosocial stress paradigm during pregnancy (CGS) to investigate the effects of psychosocial stress on maternal behavior, neuroendocrine function, and gene expression changes in molecular regulators of the HPA axis in the early postpartum period. Postpartum female mice exposed to CGS display abnormalities in maternal behavior, including fragmented and erratic maternal care patterns, and the emergence of depression and anxiety-like phenotypes. Dysregulation in postpartum HPA axis function, evidenced by blunted circadian peak and elevation of stress-induced corticosterone levels, was accompanied by increased CRH mRNA expression and a reduction in CRH receptor 1 in the paraventricular nucleus of the hypothalamus (PVN). We further observed decreased PVN expression of nuclear steroid hormone receptors associated with CRH transcription, suggesting these molecular changes could underlie abnormalities in postpartum HPA axis and behavior observed. Overall, our study demonstrates that psychosocial stress during pregnancy induces changes in neuroendocrine function and maternal behavior in the early postpartum period and introduces our CGS paradigm as a viable model that can be used to further dissect the molecular defects that lead to PPD.

Mechanisms of chronic stress influence on the brain hemodynamic in persons with employment-related chronic stress

To discuss the mechanisms by which chronic psychosocial stress (CPSS) affects the parameters of cerebral blood flow. One hundred and sixty locomotive machinists (LM) and machinist assistants (MA), whose profession is rated as one of the most stressful, were enrolled in this study. The control group consisted of 100 healthy volunteers. The activity of the stressor system was assessed by the levels of stress hormones in serum (ACTH, cortisol, adrenaline). The functional state of the endothelium was assessed by secretion of nitric oxide and endothelin-1. Doppler ultrasound was used to measure the linear velocity of blood flow in the cerebral vessels, the size of the intima-media complex of the common carotid artery, and the results of the endothelium-dependent vasodilation. Blood pressure was monitored daily. The action of CPSS is accompanied by the persistent increase in the serum cortisol levels. This process contributes to the development of vasoconstriction with the initiation of endothelial dysfunction with impaired production of nitric oxide and increased secretion of endothelin-1 and the formation of arterial hypertension. With progression of these processes, there is a decrease in cerebral blood flow. The observed increase in the size of the intima-media complex of the common carotid artery correlates with the severity of arterial hypertension and endothelial dysfunction. CPSS leads to a decrease in cerebral blood flow and subsequent development of endothelial dysfunction and arterial hypertension, which are related to high levels of stress hormones circulating in the blood. These processes lead to functional failure of the vascular endothelium.

MATERNAL PSYCHOSOCIAL STRESS AND LABOR DYSTOCIA

The aim: to study the possible role of psychosocial stressors in the emergence of anomalies of childbirth, as well as to examine their nature using the example of pregnant women who have been forcefully displaced from Donetsk and Luhansk regions of Ukraine. Materials and methods: 115 internally displaced pregnant women from Donetsk and Luhansk regions, were surveyed. All women underwent a comprehensive neuropsychological examination of their psycho-emotional status via interviews, questioning, and psychological testing (Spielberg-Haning's Situational and Personal Anxiety Scale). The following analysis of the childbirth process' nature was conducted. Results: The prevalence of high level of situational and personal anxiety by the Spielberg-Haning's test were determined in the internally displaced women. This indicates a high level of social anxiety (stress) in these pregnant women. Labours in women in this group can be characterized by 3 main features: rapid (precipitated) labour with high levels of obstetric traumatism (tear of perineum) and labour medicalization (EDA). The characteristics described above are due to such labour activity anomalies as hypertensive uterine dysfunction - the cases when the speed and strength of uterine contractions significantly exceed the normative parameters. The reasons for the high level of pain in labour in displaced women could be objecttive and subjective factors: excessive nociceptor irritation due to cervical-uterine dysfunction and impaired individual perception of pain. Conclusions: Chronic psychosocial stress has an impact on labour activity in displaced women. A mandatory standard for managing such pregnancy is psychological counselling and correction of the identified disorders.