Stress-The International Journal on the Biology of Stress最新文献

Chronic psychological stress is a known modulator of immune responses and gut microbiota composition. However, its impact on the host's inflammatory response to leptospiral lipopolysaccharide (LPS) remains insufficiently studied. This study aimed to evaluate how chronic social stress alters immune gene expression and gut microbiota composition in a rat model of leptospiral LPS-induced systemic inflammation. Male Wistar rats were divided into control (n = 6), LPS-induced inflammation group (n = 6), and LPS-induced inflammation group with chronic stress group (n = 12). Inflammation was induced by intraperitoneal injection of LPS from Leptospira interrogans (10 mg/kg). Chronic social stress was applied through 14-day overcrowding. Gene expression in peripheral blood was analyzed using RT² Profiler PCR Arrays, and gut microbiota composition was evaluated via culture-based quantification of selected taxa. Data were analyzed using Student's t-test, Kruskal-Wallis test with Dwass-Steel-Critchlow-Fligner post hoc comparisons, PCA, and Spearman's correlation. LPS administration significantly upregulated six immune-related genes compared to controls, including Il6, Il1b, Ifng, Il10, Ccl3, and Ccl5 (log₂FC ≥ 2, p < 0.05). In the LPS+Stress group, only Il10 and Tnf remained significantly upregulated above the same threshold. Principal component analysis (PCA) revealed distinct clustering of the gut microbiota profiles between the experimental groups. Significant alterations were found in the relative abundance of Bifidobacteriumspp., Lactobacillusspp., Klebsiella spp., Morganellaceae, and Alcaligenes faecalis. Notably, Klebsiellaspp. abundance positively correlated with Il1b expression in both LPS (r = 0.613, p = 0.0342) and LPS+Stress groups (r = 0.663, p = 0.0188), while Alcaligenes faecalis abundance correlated with Tnf expression in the LPS+Stress group (r = 0.616, p = 0.0330). Chronic social stress modifies the leptospiral LPS-induced immune response and contributes to significant alterations in gut microbiota. The observed correlations between specific microbial taxa and proinflammatory gene expression indicate microbiota-immune interactions that may underlie stress-associated changes in systemic inflammation.

Loneliness is increasingly recognized as a multisystem stressor that contributes to morbidity and premature mortality. This narrative review draws on searches of PubMed, PsycINFO, and Scopus (2000-2025), focusing on studies linking loneliness to neuroendocrine, immune, neural, and cardiometabolic pathways associated with allostatic load. Evidence is strongest in older adults and clinical subgroups, though emerging findings suggest relevance and mechanistic insight across community populations. Loneliness is associated with dysregulated hypothalamic-pituitary-adrenal (HPA) axis activity, elevated inflammatory biomarkers, altered amygdala reactivity, and cardiometabolic risk factors. These patterns highlight loneliness as both a psychological and biological risk factor. Limitations include heterogeneous measures and reliance on cross-sectional designs, underscoring the need for longitudinal and mechanistic studies. Addressing loneliness requires early detection through screening and implementation of evidence-based interventions, including psychosocial therapies (e.g. cognitive-behavioral and mindfulness-based approaches), social prescribing, and trauma-informed primary care. Reframing loneliness as a modifiable determinant of health underscores its importance for translational research, clinical care, and public health policy.

Stress urinary incontinence (SUI) is a serious disease for females. This study attempts to explore the role of activating transcription factor 4 (ATF4) in mechanical trauma-induced SUI fibroblast cell proliferation and apoptosis, thereby finding a candidate target for SUI treatment. A cell model simulating the condition of SUI was established for the assessment of ATF4, miR-93-3p and Smad7 expression. Cellular biological behaviors were evaluated, and levels of PCNA and Caspase-3 were measured. Mechanically, the enrichment of ATF4 on the miR-93-3p promoter was analyzed. The binding relation between ATF4 and miR-93-3p promoter and between miR-93-3p and Smad7 3'UTR was verified. The mechanism of the ATF4/miR-93-3p/Smad7 pathway in mechanical trauma-induced fibroblast proliferation and apoptosis was validated. ATF4 was upregulated in mechanical trauma-induced fibroblast, and ATF4 silencing promoted mechanical trauma-induced fibroblast proliferation and inhibited apoptosis. ATF4 bound to the miR-93-3p promoter and inhibited miR-93-3p expression. miR-93-3p targeted Smad7 3'UTR to downregulate Smad7 expression. miR-93-3p depletion or Smad7 overexpression could partially neutralize the role of ATF4 knockdown in mechanical trauma-induced fibroblast proliferation and apoptosis. ATF4 promotes apoptosis and inhibits the proliferation of mechanical trauma-induced fibroblasts via the miR-93-3p/Smad7 axis, providing a potential candidate therapeutic target for mechanical trauma-induced SUI.

Epigenetic changes affecting genes in the glucocorticoid pathway have been studied as biomarkers for major depressive disorder (MDD). The aim of this cross-sectional study was to evaluate glucocorticoid receptor (GR) gene promoter methylation levels in depressed workers exposed to occupational stress. Nuclear receptor subfamily 3 group C member 1 (NR3C1) promoter methylation levels were measured by methylation-sensitive high-resolution melting (MS-HRM) in 70 patients with MDD and 40 healthy controls. Occupational stress was evaluated in patients and controls using the Job Content Questionnaire (JCQ). NR3C1 promoter methylation levels were found to be significantly higher in MDD patients than in controls (p = 0.0001). A multiple regression analysis revealed a significant positive association between NR3C1 methylation levels and MDD diagnosis (r = 0.507, p < 0.0001), and a negative association with occupational stress (r = -0.218, p = 0.03). No differences in NR3C1 methylation levels were found between depressed patients exposed and non-exposed to previous traumatic events and the history of trauma was not a significant independent predictor of NR3C1 methylation levels. Hypothalamic-pituitary-adrenal (HPA) axis dysregulation through GR gene hypermethylation could play a key role in the pathophysiology of occupational stress-related disorders. Occupational stress could independently contribute to the epigenetic mechanisms underlying vulnerability to psychopathology. Further research is needed focusing on biomarkers for stress-related disorders as a potential tool for the diagnosis and prevention of occupational diseases.

The Trier Social Stress Test (TSST) reliably induces psychosocial stress, but its high resource demands limit its applicability in many research contexts. We evaluated a single-person videoconference TSST (vcTSST) delivered via Zoom using pre-recorded "jury" members. Forty-one healthy, German-speaking students were randomized to vcTSST (n = 21) or a structurally matched control (n = 20). Continuous heart rate and root mean square of successive interbeat differences (RMSSD) were recorded alongside visual analog scales for stress and mood across baseline, anticipation, speech, and arithmetic phases. In the vcTSST, stress and heart rate increased sharply (partial η² = .59 and .60) while mood and RMSSD decreased (partial η² = .23 and .31; all p < .001). Phase × condition interactions revealed significantly higher stress, negative affect, and heart rate in vcTSST versus control (p < .01), with no group difference in RMSSD. No participant detected the pre-recorded jury, confirming deception fidelity. The vcTSST provides a cost-effective, standardized stress paradigm, which can be used in laboratory settings and is easily adaptable for remote applications. Future studies should include neuroendocrine measures, recruit more diverse samples, and validate the protocol in online contexts.

Functional hypothalamic amenorrhea (FHA) is a form of hypogonadotropic hypogonadism that accounts for approximately 30-35% of secondary amenorrhea in women of reproductive age. This condition is characterized by anovulation due to a reduced gonadotropin-releasing hormone (GnRH) drive, activation of the hypothalamic‒pituitary‒adrenal (HPA) axis and sick euthyroid syndrome, resulting in nonorganic hypoestrogenemia, hypercortisolemia, and hypothyroidism. The stressors contributing to FHA include psychological factors such as perfectionism and mood disorders; psychosocial factors such as adverse life events and relationship conflicts; and metabolic factors such as excessive exercise and undernutrition. Stress-induced behaviors and energy deficiency may then result in the neuroendocrine triad of HPA activation, hypothalamic-pituitary-thyroid suppression, and hypothalamic-pituitary-gonadal suppression. FHA has been associated with endothelial dysfunction, a preclinical form of cardiovascular disease (CVD) characterized by physiological yet asymptomatic changes in the blood vessels that can progress to CVD. Research suggests that hypoestrogenism alone does not explain the risk for preclinical CVD in women with FHA. The combined neuroendocrine and metabolic alterations in women with FHA may predispose them to endothelial dysfunction and increase long-term CVD risk. Hypercortisolemia may be a key mediator in linking stress physiology with both reproductive suppression and cardiometabolic risk in women with FHA. This narrative review explores the psychological, psychosocial, and metabolic factors contributing to stress in young women with FHA and their potential impact on cardiovascular health.

Acute stress causes a shift from executive to automated behavior. A key executive function suffering from this shift is working memory. Working memory is mainly negatively affected in the first 10 and more than 25 minutes after acute stress. These phases coincide with increased central levels of noradrenaline and cortisol. Increased levels of both hormones can cause a relative deactivation in prefrontal areas related to working memory processing. However, so far, there is little research that investigates the complete relationship between acute stress and resulting changes in stress hormones, neural activation, and working memory processing, over time. In this study, we used functional near-infrared spectroscopy to measure prefrontal activity during an nback task in a stress (28 subjects, 7 female/21 male) and a control group (28 subjects, 10 female/18 male) once (20 minutes) before and twice (4 and 24 minutes) after a socially evaluated cold pressor test or a warm water control condition. Additionally, we regularly measured changes in salivary cortisol and α-amylase (a correlate of central noradrenaline) during the experiment. While salivary cortisol was increased starting 14 minutes after acute stress, no effect of stress on salivary α-amylase or working memory performance was found. On a neural level, we found a marginally stronger decline in 3-back-related prefrontal activity from the first to the third measurement point in the stress than in the control group. These results present tentative evidence for a negative effect of acute stress on working-memory-related prefrontal processing mediated by central cortisol levels.

Research on stress has demonstrated that the hypothalamic-pituitary-adrenal (HPA) axis contributes to major depressive disorder in youth. Hair glucocorticoids are key biological markers of chronic stress. We assessed group differences in hair cortisol and cortisone concentrations, and the cortisol/cortisone ratio between depressed adolescent women and a non-depressed comparison group. Further, within the depression group, we explored the contribution of symptom severity and clinical correlates of depression in relation to glucocorticoid concentrations. Hair samples of three centimeters for 74 adolescent women (41 in the depression group and 33 in the comparison group), aged between 12 and 19 years old, were analyzed. Depressive and anxiety symptoms were measured using the Beck Youth Inventory II and clinical correlates of depression were measured using the Childhood Trauma Questionnaire-Short Form and the Borderline Personality Features Scale for Children. No significant differences emerged between the depression group and the comparison group on hair cortisol or hair cortisone concentrations. However, groups differed significantly on the cortisol/cortisone ratio, a proposed proxy of 11-beta-hydroxysteroid dehydrogenase activity, with a higher ratio for the depression group. Within the depression group, neither symptom severity nor clinical correlates were associated with glucocorticoid concentrations. Although cross-sectional, our findings highlight the importance of future studies to test whether the group difference found in cortisol/cortisone ratio is the result of alterations in 11-beta-hydroxysteroid dehydrogenase enzymes (type 1 or 2) activity. Further research is thus needed to clarify the role of these enzymes in major depressive disorder in youth and to develop more targeted intervention strategies.

Depression commonly accompanies acute coronary syndrome (ACS), impacting up to 30% of patients and correlating with adverse outcomes. Our study aimed to assess the accuracy of clinical impression compared to the PHQ9 questionnaire for evaluating depression in ACS patients admitted to the cardiac intensive care unit. Screening for depression was conducted at least 48 hours from hospital admission and 24 hours following coronary angiography and PCI. The assessment was performed separately and in a blinded manner by the clinical assessment of the attending medical team and by the PHQ9 questionnaire. The study comprised 150 ACS patients with a mean age of 62 ± 13 years. Baseline clinical and demographic characteristics were typical for ACS patients. Based on the PHQ9 questionnaire, depressive symptoms were above the cutoff for clinical depression in 31 (20.7%) patients, with 10 (32.3%) of them experiencing moderate or severe depression (PHQ9 score >15). There were no significant differences in clinical baseline characteristics between the groups with and without clinical depression. Compared to the PHQ9 questionnaire, the medical team's assessment of depression demonstrated a reasonable specificity of 84% and low sensitivity of 32%. Negative and positive predictive values were 82.6% and 35.8%, respectively. Similar findings were observed in subgroup analyses according to gender, age, type of ACS, and history of cardiovascular disease. Depression is prevalent among ACS patients, highlighting the importance of an increased awareness of this condition. Our findings suggest that detecting clinically significant severity of depressive symptoms by the attending medical team alone may not suffice for depression assessment. Incorporating validated screening tools such as the PHQ9 questionnaire or involving psychological evaluations can enhance the accuracy of depression diagnosis in ACS patients. This multifaceted approach is crucial for ensuring comprehensive care and improving patient outcomes.

Stress occurs as a reaction to mental and emotional pressure, anxiety, or scarring. Chronic stress is defined as constant submission to these moments. It can affect several body systems, increase blood pressure, and weaken immunity, thereby interfering with physiological health processes. Thus, this study aims to evaluate the effects of chronic stress on the redox status and histomorphological parameters of salivary glands. Thirty-two albino Wistar male rats were randomly divided into two groups: chronic stress and control. Chronically stressed animals were subjected to a restraint protocol by introducing them into a polyvinyl tube for 4 hours daily for 28 days, allowing immobilization of their movements. Subsequently, the animals were euthanized for further collection of the parotid and submandibular salivary glands. The redox state of the glands was evaluated using the antioxidant capacity against peroxyl radicals (ACAP) and thiobarbituric acid reactive substances (TBARS) assays. Histological analysis was performed through morphometry of the tissues stained with hematoxylin and eosin and histochemical through picrosirius red staining. Both the parotid and submandibular glands of stressed rats exhibited oxidative stress due to a decrease in ACAP and an increase in TBARS levels. However, the parotid glands are more susceptible to harmful changes in the tissue, such as an increase in the stromal area and in the collagen area fraction, decrease in the acinar area, and smaller size of the acinus and ducts. Our results suggest that chronic stress may cause harmful modulation of the redox state of the salivary glands, with different histological repercussions.