Search Results (22)

Organisms respond to environmental stress primarily through the autonomic nervous system and hypothalamic–pituitary–adrenal (HPA) axis, regulating metabolism, psychological states, and immune function and modulating memory, reward processing, and immune responses. The HPA axis plays a central role in stress response, exhibiting distinct activation patterns under acute versus chronic social defeat stress. However, differences in physiological impacts and regulatory pathways between these stress conditions remain understudied. This study integrates RNA sequencing and behavioral analyses to reveal that acute social defeat stress triggers transient anxiety-like behaviors, accompanied by systemic inflammation and immediate-early gene (IEG) activation. In contrast, chronic social defeat stress induces long-term behavioral and physiological alterations, including neurotransmitter imbalance (e.g., reduced GABA and increased glutamate), sustained activation of maladaptive pathways (e.g., IL-17 signaling), and disrupted corticosterone synthesis. These findings highlight the dynamic regulatory role of the HPA axis under varying stress conditions, providing novel insights into mental health disorders such as anxiety and depression. The study identifies potential therapeutic targets to mitigate chronic social defeat stress effects and offers a theoretical foundation for personalized interventions. Full article

A significant portion of adolescents suffer from mental illnesses and persistent pain due to repeated stress. The components of the nervous system that link stress and pain in early life remain unclear. Prior studies in adult mice implicated the innate immune system, specifically Toll-like receptors (TLRs), as critical for inducing long-term anxiety and pain-like behaviors in social defeat stress (SDS) models. In this work, we investigated the pain and anxiety behavioral phenotypes of wild-type and TLR4-deficient juvenile mice subjected to repeated SDS and evaluated the engagement of TLR4 by measuring dimerization in the spinal cord, dorsal root ganglia, and prefrontal cortex. Male juvenile (4-week-old) mice (C57BL/6J or Tlr4^-/-) underwent six social defeat sessions with adult aggressor (CD1) mice. In WT mice, SDS promotes chronic mechanical allodynia and thermal hyperalgesia assessed via von Frey testing and the Hargreaves test, respectively. In parallel, the stressed WT mice exhibited transient anxiety-like behavior and long-lasting locomotor activity reduction in the open-field test. Tlr4^-/--stressed animals were resistant to the induction of pain-like behavior but had a remnant of anxious behavior, spending less time in the center of the arena. In WT SDS, there were concordant robust increases in TLR4 dimerization in dorsal root ganglia macrophages and spinal cord microglia, indicating TLR4 activation. These results suggest that the chronic pain phenotype and locomotor impairment induced by SDS in juvenile mice depends on TLR4 engagement evidenced by dimerization in immune cells of the dorsal root ganglia and spinal cord. Full article

Background/Objectives: Being a healthcare professional often involves exposure to complex situations that can contribute to the development of psychological problems. Evidence suggests that both mental and physical health are crucial for the well-being of these professionals, which in turn influences the quality of care they provide to patients. The main aim of this study was to examine the association between adaptive and maladaptive forms of humor and psychopathological disorders among healthcare workers. Methods: A cross-sectional and descriptive correlational design was employed. The participants consisted of 250 healthcare professionals at a general hospital. Humor styles and the presence of psychological and psychosomatic symptoms were assessed. Data were collected using the Humor Styles Questionnaire (HSQ), the Short Checklist of Symptoms (LSB-50), and sociodemographic information. Spearman correlation analysis and linear regression analysis were conducted. Results: Healthcare professionals were more inclined to use affiliative and self-enhancing humor styles compared to self-defeating and aggressive humor. Affiliative and self-enhancing humor styles were negatively correlated with psychological symptoms, whereas aggressive humor and, to a lesser extent, self-defeating humor styles showed a significantly positive correlation with most psychological symptoms. Regression analysis revealed that positive humor styles negatively predicted all severity indices of the LSB-50. In contrast, negative humor styles, particularly self-defeating humor, positively predicted the severity indices. Being female, working night shifts, and having temporary contracts were positive predictors of most global indices of the LSB-50. Conclusions: This study highlights the importance of considering different types of humor as a potential strategy for improving the mental health of healthcare professionals, as well as the influence of other independent variables related to their personal and work environment. Positive humor styles, specifically affiliative and self-enhancing humor, are associated with a lower prevalence of psychological symptoms among healthcare professionals. Negative humor styles are correlated with a higher prevalence of these symptoms. Full article

Stress is a critical factor in the development of mental disorders such as addiction, underscoring the importance of stress resilience strategies. While the ketogenic diet (KD) has shown efficacy in reducing alcohol consumption in male mice without cognitive impairment, its impact on the stress response and addiction development, especially in females, remains unclear. This study examined the KD’s effect on increasing ethanol intake due to vicarious social defeat (VSD) in female mice. Sixty-four female OF1 mice were divided into two dietary groups: standard diet (n = 32) and KD (n = 32). These were further split based on exposure to four VSD or exploration sessions, creating four groups: EXP-STD (n = 16), VSD-STD (n = 16), EXP-KD (n = 16), and VSD-KD (n = 16). KD-fed mice maintained ketosis from adolescence until the fourth VSD/EXP session, after which they switched to a standard diet. The Social Interaction Test was performed 24 h after the last VSD session. Three weeks post-VSD, the Drinking in the Dark test and Oral Ethanol Self-Administration assessed ethanol consumption. The results showed that the KD blocked the increase in ethanol consumption induced by VSD in females. Moreover, among other changes, the KD increased the expression of the ADORA1 and CNR1 genes, which are associated with mechanisms modulating neurotransmission. Our results point to the KD as a useful tool to increase resilience to social stress in female mice. Full article

The drive for a more person-centred approach in the broader field of clinical medicine is also gaining traction in chronic pain treatment. Despite current advances, a further departure from ‘business as usual’ is required to ensure that the care offered or received is not only effective but also considers personal values, goals, abilities, and day-to-day realities. Existing work typically focuses on explaining pain symptoms and the development of standardised interventions, at the risk of overlooking the broader consequences of pain in individuals’ lives and individual differences in pain responses. This review underscores the importance of considering additional factors, such as the influence of chronic pain on an individual’s sense of self. It explores innovative approaches to chronic pain management that have the potential to optimise effectiveness and offer person-centred care. Furthermore, it delves into research applying hybrid and individual formulations, along with self-monitoring technologies, to enhance pain assessment and the tailoring of management strategies. In conclusion, this review advocates for chronic pain management approaches that align with an individual’s priorities and realities while fostering their active involvement in self-monitoring and self-management. Full article

Introduction: Internal migrant workers have a great chance to experience defeat due to their low social status and economic situation. It has been reported that defeat might play a prospective role in predicting depression and anxiety; however, defeat is rarely explored among internal migrant workers due to the lack of appropriate measurement scales. The defeat scale (DS) can measure the feeling of defeat, social hierarchy reduction, and loss in social struggle. But its reliability and validity among internal migrant workers have not been reported. This study aimed to verify the content validity and structural validity of the DS among internal migrant workers in China and to explore its correlations with anxiety and depression. Methods: 1805 internal migrant workers (IMWs) were recruited by stratified multistage sampling from 16 factories in Shenzhen, China. The content validity index (CVI) was used to assess content validity. Cronbach’s coefficient alpha of each factor and the total scale were calculated to assess the reliability of DS. The scree test was used to determine the number of factors. Convergent validity and discriminant validity were estimated by calculating the average variance extracted and composite reliability. Logistic regression was performed to explore the effects of DS scores on anxiety and depression. Results: Mean score of DS among IMWs was 18.42 ± 9.40. There were 606 (33.6%) IMWs who were considered to have depression symptoms, and 524 (29.0%) IMWs were considered to have anxiety symptoms. A two-factor model was obtained and fitted well (CFI = 0.956, GFI = 0.932, IFI = 0.956, RMSEA = 0.068, SRMR = 0.052). Cronbach’s alpha reliability coefficient for the DS was 0.92. Logistic regression showed that DS scores were positively associated with anxiety and depression among IMWs. Conclusions: DS performed well among IMWs on content validity and structural validity, and it was suitable as a measurement instrument to assess defeat among this population. Defeat was positively associated with anxiety and depression and might play an important role in the mental health of IMWs. Full article

Chronic stress can affect gene expression in the hippocampus, which alters neural and cerebrovascular functions, thereby contributing to the development of mental disorders such as depression. Although several differentially expressed genes in the depressed brain have been reported, gene expression changes in the stressed brain remain underexplored. Therefore, this study examines hippocampal gene expression in two mouse models of depression induced by forced swim stress (FSS) and repeated social defeat stress (R-SDS). Transthyretin (Ttr) was commonly upregulated in the hippocampus of both mouse models, as determined by microarray, RT-qPCR, and Western blot analyses. Evaluation of the effects of overexpressed Ttr in the hippocampus using adeno-associated virus-mediated gene transfer revealed that TTR overexpression induced depression-like behavior and upregulation of Lcn2 and several proinflammatory genes (Icam1 and Vcam1) in the hippocampus. Upregulation of these inflammation-related genes was confirmed in the hippocampus obtained from mice vulnerable to R-SDS. These results suggest that chronic stress upregulates Ttr expression in the hippocampus and that Ttr upregulation may be involved in the induction of depression-like behavior. Full article

Psychosocial stress precipitates mental illnesses, such as depression, and increases the risk of other health problems, including cardiovascular diseases. In this study, we observed the effects of psychosocial stress on the histopathological features of systemic organs and tissues in a mouse psychosocial stress model, namely the subchronic and mild social defeat stress (sCSDS) model. There were several pathological findings in the tissues of both sCSDS and control mice. Mild fibrosis of the heart was observed in sCSDS mice but not in control mice. Extramedullary hematopoiesis in the spleen and hemorrhage in the lungs were observed in both the control and sCSDS mice. Focal necrosis of the liver was seen only in control mice. Furthermore, putrefactive substances in the blood plasma were analyzed because these metabolites originating from intestinal fermentation might be linked to heart fibrosis. Among them, plasma p-cresyl glucuronide and p-cresyl sulfate concentrations significantly increased owing to subchronic social defeat stress, which might influence cardiac fibrosis in sCSDS mice. In conclusion, several pathological features such as increased cardiac fibrosis and elevated plasma putrefactive substances were found in sCSDS mice. Thus, sCSDS mice are a potential model for elucidating the pathophysiology of psychosocial stress and heart failure. Full article

Upon chronic stress, a fraction of individuals shows stress resilience, which can prevent long-term mental dysfunction. The underlying molecular mechanisms are complex and have not yet been fully understood. In this study, we performed a data-driven behavioural stratification together with single-cell transcriptomics of the hippocampus in a mouse model of chronic social defeat stress. Our work revealed that in a sub-group exhibiting molecular responses upon chronic stress, the dorsal hippocampus is particularly involved in neuroimmune responses, angiogenesis, myelination, and neurogenesis, thereby enabling brain restoration and homeostasis after chronic stress. Based on these molecular insights, we applied rapamycin after the stress as a proof-of-concept pharmacological intervention and were able to substantially increase stress resilience. Our findings serve as a data resource and can open new avenues for further understanding of molecular processes underlying stress response and for targeted interventions supporting resilience. Full article

Depression has become one of the severe mental disorders threatening global human health. In this study, we first used the proteomics approach to obtain the differentially expressed proteins in the liver between naive control and chronic social defeat stress (CSDS) induced depressed mice. We have identified the upregulation of iron binding protein transferrin (TF) in the liver, the peripheral blood, and the brain in CSDS-exposed mice. Furthermore, bioinformatics analysis of the Gene Expression Omnibus (GEO) database from various mouse models of depression revealed the significantly upregulated transcripts of TF and its receptor TfR1 in multiple brain regions in depressed mice. We also used the recombinant TF administration via the tail vein to detect its permeability through the blood-brain barrier (BBB). We demonstrated the permeability of peripheral TF into the brain through the BBB. Together, these results identified the elevated expression of TF and its receptor TfR1 in both peripheral liver and the central brain in CSDS-induced depressed mice, and peripheral administration of TF can be transported into the brain through the BBB. Therefore, our data provide a compelling information for understanding the potential role and mechanisms of the cross-talk between the liver and the brain in stress-induced depression. Full article

Circadian rhythms are an inherent property of all living systems and an essential part of the external and internal temporal order. They enable organisms to be synchronized with their periodic environment and guarantee the optimal functioning of organisms. Any disturbances, so-called circadian disruptions, may have adverse consequences for health, physical and mental performance, and wellbeing. The environmental light–dark cycle is the main zeitgeber for circadian rhythms. Moreover, regular physical activity is most useful. Not only does it have general favorable effects on the cardiovascular system, the energy metabolism and mental health, for example, but it may also stabilize the circadian system via feedback effects on the suprachiasmatic nuclei (SCN), the main circadian pacemaker. Regular physical activity helps to maintain high-amplitude circadian rhythms, particularly of clock gene expression in the SCN. It promotes their entrainment to external periodicities and improves the internal synchronization of various circadian rhythms. This in turn promotes health and wellbeing. In experiments on Djungarian hamsters, voluntary access to a running wheel not only stabilized the circadian activity rhythm, but intensive wheel running even reestablished the rhythm in arrhythmic individuals. Moreover, their cognitive abilities were restored. Djungarian hamsters of the arrhythmic phenotype in which the SCN do not generate a circadian signal not only have a diminished cognitive performance, but their social memory is also compromised. Voluntary wheel running restored these abilities simultaneously with the reestablishment of the circadian activity rhythm. Intensively exercising Syrian hamsters are less anxious, more resilient to social defeat, and show less defensive/submissive behaviors, i.e., voluntary exercise may promote self-confidence. Similar effects were described for humans. The aim of the present paper is to summarize the current knowledge concerning the effects of physical activity on the stability of the circadian system and the corresponding consequences for physical and mental performance. Full article

Background: Migrant workers are in a socially disadvantaged position and thus suffer from more stress and mental health disorders, resulting in a high risk of suicidal ideation. This study aimed to explore the association between psychosocial problems and suicidal ideation, and the syndemic effect of concurrent psychosocial problems on suicidal ideation among migrant workers. Methods: We conducted a cross-sectional study and recruited 1805 migrant workers in Shenzhen, China. Each participant completed a self-administered questionnaire to report sociodemographic information and mental health status. Univariate and multivariate logistic regression were used to explore the association between psychosocial variables and suicidal ideation, and their syndemic effect on suicidal ideation. Results: The prevalence of suicidal ideation among migrant workers was 7.5%. All selected psychosocial variables were independently associated with suicidal ideation. Multivariate logistic regression analysis showed that three psychosocial variables were associated with suicidal ideation: anxiety (ORm: 1783, 95% CI: 1.089–2.920), entrapment (ORm: 2.064, 95% CI: 1.257–3.388), and defeat (ORm: 2.572, 95% CI: 1.612–4.103). Various mental health issues can exist simultaneously to increase the risk of suicidal ideation (AOR: 5.762, 95% CI: 3.773–8.802). Workers with more psychosocial problems were more likely to have suicidal ideation. Conclusions: The association between poor mental health and suicidal ideation should not be overlooked among migrant workers. The co-occurring or syndemic effect of psychosocial problems may increase the risk of suicidal ideation. Full article

This study investigated the role of perceived stigmatization in the relationship between humor styles and coping with stress among young women suffering from stigma due to obesity. In the 21st century, obesity is an increasing global health issue with many physical and mental consequences for obese women. As a chronic stigmatizing disease, it requires that the affected individuals cope with social consequences; women with obesity are more prone to such consequences than men. Humor fosters the breaking of stereotypes and alleviating the consequences of stigmatization. A total of 127 young adult women (age M = 25.74, SD = 2.73) participated in the study (n = 54 with overfat and n = 73 with healthy fat). Participants filled out the Humor Styles Questionnaire, Perceived Stigmatization Questionnaire, and the Brief COPE Scale. Anthropometric data were gathered using a body composition analyzer. Results indicate that, when perceiving hostile behaviors toward themselves and using humor as a coping strategy, women with overfat select maladaptive styles of humor (i.e., self-defeating and aggressive styles). Women with overfat were also more likely to use humor as a coping strategy in difficult situations. Furthermore, none of the participants were satisfied with their body mass. At the same time, among women without obesity, a lack of compliments was not treated as a problem, even if they had high body fat. Full article

Piccolo, a presynaptic cytomatrix protein, plays a role in synaptic vesicle trafficking in the presynaptic active zone. Certain single-nucleotide polymorphisms of the Piccolo-encoding gene PCLO are reported to be associated with mental disorders. However, a few studies have evaluated the relationship between Piccolo dysfunction and psychotic symptoms. Therefore, we investigated the neurophysiological and behavioral phenotypes in mice with Piccolo suppression in the medial prefrontal cortex (mPFC). Downregulation of Piccolo in the mPFC reduced regional synaptic proteins, accompanied with electrophysiological impairments. The Piccolo-suppressed mice showed an enhanced locomotor activity, impaired auditory prepulse inhibition, and cognitive dysfunction. These abnormal behaviors were partially ameliorated by the antipsychotic drug risperidone. Piccolo-suppressed mice received mild social defeat stress showed additional behavioral despair. Furthermore, the responses of these mice to extracellular glutamate and dopamine levels induced by the optical activation of mPFC projection in the dorsal striatum (dSTR) were inhibited. Similarly, the Piccolo-suppressed mice showed decreased depolarization-evoked glutamate and -aminobutyric acid elevations and increased depolarization-evoked dopamine elevation in the dSTR. These suggest that Piccolo regulates neurotransmission at the synaptic terminal of the projection site. Reduced neuronal connectivity in the mPFC-dSTR pathway via suppression of Piccolo in the mPFC may induce behavioral impairments observed in schizophrenia. Full article

As daily lifestyle is closely associated with mental illnesses, diet-based preventive approaches are receiving attention. Supplementation with hop bitter acids such as iso-α-acids (IAA) and mature hop bitter acids (MHBA) improves mood states in healthy older adults. However, the underlying mechanism remains unknown. Since acute oral consumption with IAA increases dopamine levels in hippocampus and improves memory impairment via vagal nerve activation, here we investigated the effects of chronic administration of hop bitter acids on the dopaminergic activity associated with emotional disturbance in a mouse model of repeated social defeat stress (R-SDS). Chronic administration of IAA and MHBA significantly increased dopaminergic activity based on the dopamine metabolite to dopamine ratio in the hippocampus and medial prefrontal cortex following R-SDS. Hippocampal dopaminergic activity was inversely correlated with the level of R-SDS-induced social avoidance with or without IAA administration. Therefore, chronic treatment with hop bitter acids enhances stress resilience-related hippocampal dopaminergic activity. Full article