Stressors in Atopic Dermatitis.

As with other inflammatory skin disorders, atopic dermatitis has a tendency to cause stress and also be exacerbated by it. Patients with atopic dermatitis have several disease-associated stressors, some of which include physical discomfort due to itching and altered appearance due to flare-ups. These stressors have been shown to effect patients psychosocially by altering sleep patterns, decreasing self-esteem, and interfering with interpersonal relationships. In combination with its direct effect on patients, atopic dermatitis also causes stress for parents and caregivers. Studies suggest that atopic dermatitis is strongly correlated with co-sleeping habits, which can negatively impact the health and mood of parents or caregivers. It has also been reported to interfere with the formation of a strong mother-child relationship. In order to optimize treatment for patients with atopic dermatitis, it is important to note the impact that it has on quality of life. By implementing patient counseling, sleep-targeted therapies, and the use of quality of life (QoL) indices, atopic dermatitis patients and caregivers have the potential to experience greater satisfaction with treatment.

An Overview on Atopic Dermatitis, Oxidative Stress, and Psychological Stress: Possible Role of Nutraceuticals as an Additional Therapeutic Strategy.

Atopic dermatitis (AD) is a chronic inflammatory skin condition with a considerable impact on patients' quality of life. Its etiology is multifactorial and, among the predisposing factors, a role is played by oxidative stress. Pollution, recurrent infections, and psychological stress contribute to oxidative stress, amplifying the production of proinflammatory cytokines and worsening barrier damage. There are various oxidative stress mechanisms involved in the pathogenesis of AD. Moreover, AD often appears to be associated with psychological disorders such as alexithymia, depression, and anxiety due to severe itching and related insomnia, as well as social distress and isolation. The increasing incidence of AD requires the evaluation of additional therapeutic approaches in order to reduce the psychological burden of this condition. Our review aims to evaluate the role of some nutraceuticals in AD treatment and its related psychological comorbidities. The combination of some natural compounds (flavonoids, alkaloids, terpenes, isothiocyanates) with traditional AD treatments might be useful in improving the effectiveness of therapy, by reducing chronic inflammation and preventing flare-ups, and in promoting corticosteroid sparing. In addition, some of these nutraceuticals also appear to have a role in the treatment of psychological disorders, although the underlying oxidative stress mechanisms are different from those already known for AD.

Cortico-limbic interactions and carotid atherosclerotic burden during chronic stress exposure.

BACKGROUND AND AIMS: Chronic stress associates with cardiovascular disease, but mechanisms remain incompletely defined. Advanced imaging was used to identify stress-related neural imaging phenotypes associated with atherosclerosis. METHODS: Twenty-seven individuals with post-traumatic stress disorder (PTSD), 45 trauma-exposed controls without PTSD, and 22 healthy controls underwent 18F-fluorodeoxyglucose positron emission tomography/magnetic resonance imaging (18F-FDG PET/MRI). Atherosclerotic inflammation and burden were assessed using 18F-FDG PET (as maximal target-to-background ratio, TBR max) and MRI, respectively. Inflammation was assessed using high-sensitivity C-reactive protein (hsCRP) and leucopoietic imaging (18F-FDG PET uptake in spleen and bone marrow). Stress-associated neural network activity (SNA) was assessed on 18F-FDG PET as amygdala relative to ventromedial prefrontal cortex (vmPFC) activity. MRI diffusion tensor imaging assessed the axonal integrity (AI) of the uncinate fasciculus (major white matter tract connecting vmPFC and amygdala). RESULTS: Median age was 37 years old and 54% of participants were female. There were no significant differences in atherosclerotic inflammation between participants with PTSD and controls; adjusted mean difference in TBR max (95% confidence interval) of the aorta 0.020 (-0.098, 0.138), and of the carotids 0.014 (-0.091, 0.119). Participants with PTSD had higher hsCRP, spleen activity, and aorta atherosclerotic burden (normalized wall index). Participants with PTSD also had higher SNA and lower AI. Across the cohort, carotid atherosclerotic burden (standard deviation of wall thickness) associated positively with SNA and negatively with AI independent of Framingham risk score. CONCLUSIONS: In this study of limited size, participants with PTSD did not have higher atherosclerotic inflammation than controls. Notably, impaired cortico-limbic interactions (higher amygdala relative to vmPFC activity or disruption of their intercommunication) associated with carotid atherosclerotic burden. Larger studies are needed to refine these findings.

A Self-Reported Study on Explanatory Variables of Stress in Multiple Sclerosis Patients: Exploring the Effect of Physical Conditions and Emotion Regulation Processes.

BACKGROUND: Multiple sclerosis (MS)-linked stress is frequent, multidetermined and facilitates the onset/exacerbation of MS. However, few explanatory models of stress analysed the joint explanatory effect of emotion regulation and clinical outcomes of MS in those patients. OBJECTIVE: This study explored whether self-reported MS-related conditions (number of relapses, fatigue and global disability) and specific emotion regulation processes (experiential avoidance and self-compassion) explain stress symptoms in MS patients. METHODS: The MS sample comprised 101 patients with MS diagnosis receiving treatment in hospitals and recruited through the Portuguese MS Society. The no-MS sample included 134 age-, sex- and years of education-matched adults without MS recruited from the general Portuguese population. Both samples did not report other neurological disorders. Data were collected using self-response measures. RESULTS: All potential explanatory variables differed significantly between samples, with higher scores found in MS patients. In MS clinical sample, those variables and years of education correlated with stress symptoms and predicted stress symptoms in simple linear regression models. These results allowed their selection as covariates in a multiple linear regression model. Years of education, the number of relapses, fatigue and experiential avoidance significantly predicted 51% of stress symptoms' total variance. CONCLUSIONS: This study provides preliminary evidence on the importance of clinicians and researchers considering the simultaneous contribution of years of education, the number of perceived relapses, fatigue and experiential avoidance as factors that can increase vulnerability to stress in MS patients. Psychological intervention programmes that tackle these factors and associated stress symptomatology should be implemented.

Dexmedetomidine attenuates acute stress-impaired learning and memory in mice by maintaining the homeostasis of intestinal flora.

Dexmedetomidine (Dex) has been used in surgery to improve patients' postoperative cognitive function. However, the role of Dex in stress-induced anxiety-like behaviors and cognitive impairment is still unclear. In this study, we tested the role of Dex in anxiety-like behavior and cognitive impairment induced by acute restrictive stress and analyzed the alterations of the intestinal flora to explore the possible mechanism. Behavioral and cognitive tests, including open field test, elevated plus-maze test, novel object recognition test, and Barnes maze test, were performed. Intestinal gut Microbe 16S rRNA sequencing was analyzed. We found that intraperitoneal injection of Dex significantly improved acute restrictive stress-induced anxiety-like behavior, recognition, and memory impairment. After habituation in the environment, mice (male, 8 weeks, 18-23 g) were randomly divided into a control group (control, N = 10), dexmedetomidine group (Dex, N = 10), AS with normal saline group (AS + NS, N = 10) and AS with dexmedetomidine group (AS + Dex, N = 10). By the analysis of intestinal flora, we found that acute stress caused intestinal flora disorder in mice. Dex intervention changed the composition of the intestinal flora of acute stress mice, stabilized the ecology of the intestinal flora, and significantly increased the levels of Blautia (A genus of anaerobic bacteria) and Coprobacillus. These findings suggest that Dex attenuates acute stress-impaired learning and memory in mice by maintaining the homeostasis of intestinal flora.

Positive psychosocial factors may protect against perceived stress in people with systemic lupus erythematosus with and without trauma history.

OBJECTIVE: Trauma history is associated with SLE onset and worse patient-reported outcomes; perceived stress is associated with greater SLE disease activity. Stress perceptions vary in response to life events and may be influenced by psychosocial factors. In an SLE cohort, we examined whether stressful events associated with perceived stress, whether psychosocial factors affected perceived stress, and whether these relationships varied by prior trauma exposure. METHODS: This is a cross-sectional analysis of data from the California Lupus Epidemiology Study, an adult SLE cohort. Multivariable linear regression analyses controlling for age, gender, educational attainment, income, SLE damage, comorbid conditions, glucocorticoids ≥7.5 mg/day and depression examined associations of recent stressful events (Life Events Inventory) and positive (resilience, self-efficacy, emotional support) and negative (social isolation) psychosocial factors with perceived stress. Analyses were stratified by lifetime trauma history (Brief Trauma Questionnaire (BTQ)) and by adverse childhood experiences (ACEs) in a subset. RESULTS: Among 242 individuals with SLE, a greater number of recent stressful events was associated with greater perceived stress (beta (95% CI)=0.20 (0.07 to 0.33), p=0.003). Positive psychosocial factor score representing resilience, self-efficacy and emotional support was associated with lower perceived stress when accounting for number of stressful events (-0.67 (-0.94 to -0.40), p<0.0001); social isolation was associated with higher stress (0.20 (0.14 to 0.25), p<0.0001). In analyses stratified by BTQ trauma and ACEs, associations of psychosocial factors and perceived stress were similar between groups. However, the number of recent stressful events was significantly associated with perceived stress only for people with BTQ trauma (0.17 (0.05 to 0.29), p=0.0077) and ACEs (0.37 (0.15 to 0.58), p=0.0011). CONCLUSION: Enhancing positive and lessening negative psychosocial factors may mitigate deleterious perceived stress, which may improve outcomes in SLE, even among individuals with a history of prior trauma who may be more vulnerable to recent stressful events.

Cathepsin K deficiency prevented stress-related thrombosis in a mouse FeCl3 model.

BACKGROUND: Exposure to chronic psychological stress (CPS) is a risk factor for thrombotic cardiocerebrovascular diseases (CCVDs). The expression and activity of the cysteine cathepsin K (CTSK) are upregulated in stressed cardiovascular tissues, and we investigated whether CTSK is involved in chronic stress-related thrombosis, focusing on stress serum-induced endothelial apoptosis. METHODS AND RESULTS: Eight-week-old wild-type male mice (CTSK+/+) randomly divided to non-stress and 3-week restraint stress groups received a left carotid artery iron chloride3 (FeCl3)-induced thrombosis injury for biological and morphological evaluations at specific timepoints. On day 21 post-stress/injury, the stress had enhanced the arterial thrombi weights and lengths, in addition to harmful alterations of plasma ADAMTS13, von Willebrand factor, and plasminogen activation inhibitor-1, plus injured-artery endothelial loss and CTSK protein/mRNA expression. The stressed CTSK+/+ mice had increased levels of injured arterial cleaved Notch1, Hes1, cleaved caspase8, matrix metalloproteinase-9/-2, angiotensin type 1 receptor, galactin3, p16IN4A, p22phox, gp91phox, intracellular adhesion molecule-1, TNF-α, MCP-1, and TLR-4 proteins and/or genes. Pharmacological and genetic inhibitions of CTSK ameliorated the stress-induced thrombus formation and the observed molecular and morphological changes. In cultured HUVECs, CTSK overexpression and silencing respectively increased and mitigated stressed-serum- and H2O2-induced apoptosis associated with apoptosis-related protein changes. Recombinant human CTSK degraded γ-secretase substrate in a dose-dependent manor and activated Notch1 and Hes1 expression upregulation. CONCLUSIONS: CTSK appeared to contribute to stress-related thrombosis in mice subjected to FeCl3 stress, possibly via the modulation of vascular inflammation, oxidative production and apoptosis, suggesting that CTSK could be an effective therapeutic target for CPS-related thrombotic events in patients with CCVDs.

Non-alcoholic fatty liver disease and coexisting depression, anxiety and/or stress in adults: a systematic review and meta-analysis.

Background: Non-alcoholic fatty liver disease (NAFLD) is a common chronic liver disease, affecting 25-30% of the general population globally. The condition is even more prevalent in individuals with obesity and is frequently linked to the metabolic syndrome. Given the known associations between the metabolic syndrome and common mental health issues, it is likely that such a relationship also exists between NAFLD and mental health problems. However, studies in this field remain limited. Accordingly, the aim of this systematic review and meta-analysis was to explore the prevalence of one or more common mental health conditions (i.e., depression, anxiety, and/or stress) in adults with NAFLD. Methods: PubMed, EBSCOhost, ProQuest, Ovid, Web of Science, and Scopus were searched in order to identify studies reporting the prevalence of depression, anxiety, and/or stress among adults with NAFLD. A random-effects model was utilized to calculate the pooled prevalence and confidence intervals for depression, anxiety and stress. Results: In total, 31 studies were eligible for inclusion, involving 2,126,593 adults with NAFLD. Meta-analyses yielded a pooled prevalence of 26.3% (95% CI: 19.2 to 34) for depression, 37.2% (95% CI: 21.6 to 54.3%) for anxiety, and 51.4% (95% CI: 5.5 to 95.8%) for stress among adults with NAFLD. Conclusion: The present findings suggest a high prevalence of mental health morbidity among adults with NAFLD. Given the related public health impact, this finding should prompt further research to investigate such associations and elucidate potential associations between NAFLD and mental health morbidity, exploring potential shared underlying pathophysiologic mechanisms. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42021288934.

Effectiveness of stress management interventions for nursing students: A systematic review and meta-analysis.

Elevated stress levels are related to diminished mental health, potentially leading to decreased well-being and performance of nursing students. While researchers have focused on developing stress management interventions, there is a need to synthesize the evidence. A systematic review with meta-analysis was conducted to assess the evidence for the effectiveness of stress management interventions in nursing students. A systematic literature search identified controlled stress management interventions employing a validated psychological or physiological stress measure. Forty-one studies were included, with 36 forming a pool of 2715 participants in the meta-analysis. The overall effect on psychological stress was positive. Intervention type, delivery modality, intervention duration in weeks, and number of sessions were moderators of intervention effectiveness, with more significant effects for mind-body programs, on-site delivery methods, durations of 9-12 weeks, and 15-30 sessions. For physiological stress, the biomarkers of blood pressure, heart rate, and cortisol levels decreased significantly. Future research is necessary for promising outcomes related to currently underrepresented indicators and to investigate the long-term effects of interventions.

Electroacupuncture alleviates the symptom of depression in mice by regulating the cGAS-STING-NLRP3 signaling.

PURPOSE: To investigate the therapeutic effect of electroacupuncture (EA) on chronic and unpredictable mild stress (CUMS)-induced depression in mice and the underlying mechanism. METHODS: Male C57BL/6 mice were randomly divided into 6 groups: Control, CUMS, CUMS+EA-placebo, CUMS+EA, CUMS+ ad-NC, CUMS+ ad-cGAS-shRNA. CUMS was utilized to establish the depression model in mice. The behavioral changes were determined by the forced swimming, open field, and sucrose preference experiments. The pathological changes in the hippocampus tissue were evaluated by HE staining. The release of TNF-α, IL-1ß, IL-6, 5-HT, and NE in the hippocampus tissue was determined by ELISA. IBA-1 expression detected by the immunofluorescence was used to represent the activity of microglia. Western blot and RT-PCR were utilized to measure the expression of Bax, bcl-2, cGAS, STING, TBK1, IRF3, and NLRP3. RESULTS: The depression behavior in CUMS mice was significantly alleviated by the treatment of EA and cGAS-shRNA, accompanied by ameliorated hippocampus pathological changes, declined production of TNF-α, IL-1ß, and IL-6, elevated secretion of 5-HT and NE, and inhibition on the activity of microglia. Furthermore, significantly elevated expression level of Bax, cGAS, STING, TBK1, IRF3, and NLRP3 and declined expression level of bcl-2 were observed in the CUMS+EA and CUMS+ ad-cGAS-shRNA groups. CONCLUSIONS: EA significantly mitigated the symptom of depression in mice, which was closely associated with the repressed neuroinflammation, increased monoamine concentration, inactivated microglia, and inhibited cGAS-STING-NLRP3 signaling.

A new predictive scoring model for globus pharyngeus in patients with gastroesophageal reflux disease.

BACKGROUND: Globus pharyngeus is a clinical condition, wherein, a patient senses a lump or a foreign body in the throat with a tightening or choking feeling. A strong association between globus pharyngeus and gastroesophageal reflux disease (GERD) was reported. Therefore, we sought to investigate the predictive factors of globus pharyngeus in patients with established GERD and fit a predictive scoring model for globus pharyngeus. METHODS: In this case-control study, 143 patients having globus pharyngeus along with GERD ( case ) and 109 patients having globus pharyngeus without GERD ( control ) were enrolled. Data comprising demographics, comorbidities, and psychosocial stress levels were recorded. The predictive factors of globus pharyngeus in patients with GERD were unraveled, and a predictive scoring model was fit for globus pharyngeus. RESULTS: Proton pump inhibitor usage in the case group was significantly higher compared to controls (63.63% vs 24.78%, P < 0.001), and differences in Hiatus Hernia and Stress levels were highly significant between the two groups ( P < 0.001). Multivariate logistic regression revealed that variates, Hiatus Hernia, psychosocial stress, and age were highly significant ( P < 0.001) independent predictors of globus pharyngeus. Using the regression coefficients of all the independent predictor variables, a predictive scoring model was fitted, which yielded an area under receiver operating characteristic (AUROC) curve of 78.9. CONCLUSION: Hiatus hernia, psychosocial stress, and age are significant independent predictors of globus pharyngeus in GERD, and our predictive scoring model may help in identifying patients at higher odds of experiencing globus pharyngeus and modulate treatment accordingly.

Chronic unpredictable mild stress increases serum aldosterone without affecting corticosterone levels and induces hepatic steatosis and renal injury in young adult male rats.

Stress is often associated with anxiety and depressive symptoms in adolescents. Stress is associated with components of metabolic syndrome and inflammation. The present study hypothesizes that aldosterone, more than corticosterone, promotes chronic stress-hepatic steatosis and fibrosis, as well as renal inflammation and fibrosis in young adult rats. Thirty-two young adult male Wistar rats of 51 days old were divided into four groups (n = 8 per group): Control (C), chronic unpredictable mild stress (CUMS), control plus vehicle (C plus veh), CUMS plus eplerenone, a selective aldosterone blocker (CUMS plus EP). On postnatal day 51, eplerenone was administered orally through a gastric tube two hours before the start of the stress test. The CUMS paradigm was administered once daily at different times, with no repetition of the stressor sequence for four weeks. Renal inflammation and fibrosis were measured, as well as liver glycogen, triacylglycerol, and fibrosis levels. The serum concentrations of corticosterone, aldosterone, sodium, and creatinine were measured in urine and serum. The CUMS group showed a high level of serum aldosterone without affecting the level of corticosterone, increased urinary sodium, tubular atrophy, glomerular sclerosis, the presence of inflammation, and fibrosis, without affecting creatinine, increased glycogen content, triacylglycerol, and moderate fibrosis in the liver, and treatment with eplerenone prevented the inflammation, fibrosis, glycogen, and triacylglycerol. Our results show that chronic stress-induced aldosterone promotes hepatic steatosis and renal injury more than corticosterone. The prevention by eplerenone supports our hypothesis.

Predictors of Burden for First-Ever Stroke Survivor's Long-Term Caregivers: A Study of KOSCO.

Long-term changes in caregiver burden should be clarified considering that extended post-stroke disability can increase caregiver stress. We assessed long-term changes in caregiver burden severity and its predictors. This study was a retrospective analysis of the Korean Stroke Cohort for Functioning and Rehabilitation. Patients with an acute first-ever stroke were enrolled from August 2012 to May 2015. Data were collected at 6 months and 6 years after stroke onset. The caregiver burden was measured with a subjective caregiver burden questionnaire based on the Korean version of the Caregiver Burden Inventory. The caregivers' characteristics and patients' clinical and functional status were also examined at each follow-up. A high caregiver burden, which suggests a risk of burnout, was reported by 37.9% and 51.7% of caregivers at 6 months and 6 years post-stroke, respectively. Both the caregiver burden total score and proportion of caregivers at risk of burnout did not decrease between 6 months and 6 years. The patients' disability (OR = 11.60; 95% CI 1.58-85.08; p = 0.016), caregivers' self-rated stress (OR = 0.03; 95% CI 0.00-0.47; p = 0.013), and caregivers' quality of life (OR = 0.76; 95% CI 0.59-0.99; p = 0.042) were burden predictors at 6 months. At 6 years, only the patients' disability (OR = 5.88; 95% CI 2.19-15.82; p < 0.001) and caregivers' psychosocial stress (OR = 1.26; 95% CI 1.10-1.44; p = 0.001) showed significance. Nearly half of the caregivers were at risk of burnout, which lasted for 6 years after stroke onset. The patients' disability and caregivers' stress were burden predictors in both subacute and chronic phases of stroke. The findings suggest that consistent interventions, such as emotional support or counseling on stress relief strategies for caregivers of stroke survivors, may reduce caregiver burden. Further research is needed to establish specific strategies appropriate for Korean caregivers to alleviate their burden in caring for stroke patients.

Hydroxytyrosol ameliorates stress-induced liver injury through activating autophagy via HDAC1/2 inhibition.

Hydroxytyrosol (HT), a phenolic extra-virgin olive oil compound used as a food supplement, has been recognized to protect liver function and alleviate stress-induced depressive-like behaviors. However, its protective effects against stress-induced liver injury (SLI) remain unknown. Here, the anti-SLI effect of HT was evaluated in mice with chronic unpredictable mild stress-induced SLI. Network pharmacology combined with molecular docking was used to clarify the underlying mechanism of action of HT against SLI, followed by experimental verification. The results showed that accompanying with the alleviation of HT on stress-induced depressive-like behaviors, HT was confirmed to exert the protective effects against SLI, as represented by reduced serum corticosterone (CORT), aspartate aminotransferase and alanine aminotransferase activities, as well as repair of liver structure, inhibition of oxidative homeostasis collapse, and inflammation reaction in the liver. Furthermore, core genes including histone deacetylase 1 and 2 (HDAC1/2), were identified as potential targets of HT in SLI based on bioinformatic screening and simulation. Consistently, HT significantly inhibited HDAC1/2 expression to maintain mitochondrial dysfunction in an autophagy-dependent manner, which was confirmed in a CORT-induced AML-12 cell injury and SLI mice models combined with small molecule inhibitors. We provide the first evidence that HT inhibits HDAC1/2 to induce autophagy in hepatocytes for maintaining mitochondrial dysfunction, thus preventing inflammation and oxidative stress for exerting an anti-SLI effect. This constitutes a novel therapeutic modality to synchronously prevent stress-induced depression-like behaviors and liver injury, supporting the advantaged therapeutic potential of HT.

Gastrodin alleviates the deterioration of depressive-like behavior and glucolipid metabolism promoted by chronic stress in type 2 diabetic mice.

The growing burden of psychological stress among diabetes patients has contributed to a rising incidence of depression within this population. It is of significant importance to conduct research on the impact of stress on diabetes patients and to explore potential pharmacological interventions to counteract the stress-induced exacerbation of their condition. Gastrodin is a low molecular weight bioactive compound extracted from the rhizome of Gastrodiae elata Blume, and it may be a preventive strategy for diabetes and a novel treatment for depression symptoms. However, its relevant pharmacological mechanisms for protecting against the impacts of psychological stress in diabetic patients are unclear. In this study, we performed 5 weeks CUMS intervention and simultaneously administered gastrodin (140 mg/kg, once daily) on T2DM mice, to investigate the potential protective effects of gastrodin. The protective effect of gastrodin was evaluated by behavioral tests, biochemical analysis, histopathological examination, RT-qPCR and gut microbiota analysis. We found that the depressive-like behavior and glucolipid metabolism could be deteriorated by chronic stress in type 2 diabetic mice, while gastrodin showed a protective effect against these exacerbations by regulating HPA hormones, activating FXR and Cyp7a1, reducing inflammatory and oxidative stress responses, and regulating ileal gut microbiota abundance. Gastrodin might be a potential therapeutic agent for mitigating the deterioration of diabetes conditions due to chronic stress.

Coprococcus eutactus screened from healthy adolescent attenuates chronic restraint stress-induced depression-like changes in adolescent mice: Potential roles in the microbiome and neurotransmitter modulation.

The onset of depression commonly occurs in adolescence; therefore, depressive prevention and intervention are pivotal during this period. It is becoming evident that neurotransmitter imbalance and gut microbiota dysbiosis are prominent causes of depression. However, the underlying links and mechanisms remain poorly understood. In this study, with 16S ribosomal RNA gene sequencing, genus Coprococcus markedly differentiated between the healthy and unmedicated depressive adolescents. Based on this, transplantation of Coprococcus eutactus (C.e.) was found to dramatically ameliorate the chronic restraint stress (CRS) induced depression-like changes and prevent synaptic loss and glial-stimulated neuroinflammation in mice. The Ultra-high performance liquid chromatography tandem mass spectrometry analysis (UHPLC-MS/MS) further showed that neurotoxic neurotransmitters in kynurenine pathway (KP) such as 3-hydroxykynurenine (3-HK) and 3-hydroxyanthranilic acid (3-HAA) decreased in mouse brains, mechanistically deciphering the transfer of the tryptophan metabolic pathway to serotonin metabolic signaling in the brain after C.e. treatment, which was also verified in the colon. Molecularly, blockage of KP activities mediated by C.e. was ascribed to the restraint of the limit-step enzymes responsible for kynurenine, 3-HK, and quinolinic acid generation. In the colon, C.e. treatment significantly recovered goblet cells and mucus secretion in CRS mice which may ascribe to the rebalance of the disordered gut microbiota, especially Akkermansia, Roseburia, Rikenella, Blautia, and Alloprevotella. Taken together, the current study reveals for the first time the beneficial effects and potential mechanisms of C.e. in ameliorating CRS-induced depression, unraveling the direct links between C.e. treatment and neurotransmitter rebalance, which may provide efficacious therapeutic avenues for adolescent depressive intervention.

Effects of Psychological Stress on Spontaneous Itch and Mechanical Alloknesis of Atopic Dermatitis.

Atopic dermatitis (AD), a chronic inflammatory skin disease, manifests as an intractable itch. Psychological stress has been suggested to play a role in the onset and worsening of AD symptoms. However, the pathophysiological relationships between psychological stressors and cutaneous manifestations remain unclear. To elucidate the mechanisms underlying the stress-related exacerbation of itch, we investigated the effects of water stress, restraint stress and repeated social defeat stress on itch-related scratching behaviour, mechanical alloknesis and dermatitis in male NC/Nga mice with AD-like symptoms induced by the repeated application of ointment containing Dermatophagoides farina body. NC/Nga mice with AD-like symptoms were subjected to water stress, restraint stress and repeated social defeat stress, and their scratching behaviour, sensitivity to mechanical stimuli (mechanical alloknesis) and severity of  dermatitis were evaluated. Social defeat stress+ Dermatophagoides farina body-treated mice exposed to stress showed slower improvements in or the exacerbation of AD-like symptoms, including dermatitis and itch. In the mechanical alloknesis assay, the mechanical alloknesis scores of social defeat stress+ Dermatophagoides farina body-treated mice exposed to stress were significantly higher than those of non-exposed social defeat stress+ Dermatophagoides farina body- and social defeat stress-treated mice. These results suggest that psychological stress delays improvements in dermatitis by exacerbating itch hypersensitivity in AD.