Stress-related Mental Disorders Research Articles

Asoprisnil as a Novel Ligand Interacting with Stress-Associated Glucocorticoid Receptor

Background/objective: The glucocorticoid receptor (GR) is critical in regulating cortisol production during stress. This makes it a key target for treating conditions associated with hypothalamic–pituitary–adrenal (HPA) axis dysregulation, such as mental disorders. This study explores novel ligands beyond mifepristone for their potential to modulate GR with improved efficacy and safety. By investigating these interactions, we seek to identify new pharmacotherapeutic options for stress-related mental illness. Methods: The ligands asoprisnil, campestanol, and stellasterol were selected based on structural similarities to mifepristone (reference ligand) and evaluated for pharmacological and ADME (absorption, distribution, metabolism, and excretion) properties using the SwissADME database. Molecular docking with AutoDock 4.2.6 and molecular dynamics simulations were performed to investigate ligand–protein interactions with the human glucocorticoid receptor, and binding free energies were calculated using MMPBSA. Results: Pharmacokinetic analysis revealed that asoprisnil exhibited high gastrointestinal absorption and obeyed Lipinski’s rule, while mifepristone crossed the blood–brain barrier. Toxicological predictions showed that mifepristone was active for neurotoxicity and immunotoxicity, while asoprisnil, campestanol, and stellasterol displayed lower toxicity profiles. Asoprisnil demonstrated the highest stability in molecular dynamics simulations, with the highest negative binding energy of −62.35 kcal/mol, when compared to mifepristone, campestanol, and stellasterol, with binding energies of −57.08 kcal/mol, −49.99 kcal/mol, and −46.69 kcal/mol, respectively. Conclusion: This makes asoprisnil a potentially favourable therapeutic candidate compared to mifepristone. However, further validation of asoprisnil’s interaction, efficacy, and safety in stress-related mental disorders through experimental studies and clinical trials is needed.

Increase in short-term and long-term stress-associated mental illness after Jiji earthquake in Taiwan: A twenty-year longitudinal population-based cohort study (1999–2019)

BackgroundEarthquakes have caused profound physical and mental health impacts in human history. The Jiji earthquake, which had a magnitude of 7.6 on the Richter scale, occurred on 21 September 1999 in Taiwan. A close follow-up on the mental health status of affected adults after major natural disasters to construct the short-term and long-term risk and prevalence of stress-associated mental illnesses has not been performed by using the nationwide health databases. MethodsThis population-based cohort study included 468,804 adults affected by Jiji earthquake spanning from 2000 to 2019 who were matched at a 1:4 ratio with unaffected individuals based on age and sex (n = 1,875,216). Employing a subdistribution hazard regression analysis, we assessed the incidence of sleep, anxiety, and depressive disorders after Jiji earthquake. Corrections for multiple comparisons were carried out using the Benjamini–Hochberg procedure. ResultsAffected adults experienced an increased incidence of short-term (approximately twice) stress-associated psychiatric disorders. The risk of the post-traumatic stress disorder (PTSD) is significantly higher in the affected adults (40–64 years: aSHR: 92.0; ≥65 years: aSHR: 96.7, p < 0.0001). Middle-aged (aged 40–64 years) male adults presented with significantly more short-term (< one year) and long-term (up to 20 years) stress-related mental illnesses, i.e., insomnia, anxiety, and depressive disorders, than individuals in the control group. ConclusionsAn earthquake has significant short and long-term effects on sleep quality, anxiety, and depressive disorders in affected adults. Optimal short and long-term close monitoring is needed to deploy medical resources and socioeconomic support to relieve mental stress burdens.

Machine Learning, Deep Learning, and Data Preprocessing Techniques for Detecting, Predicting, and Monitoring Stress and Stress-Related Mental Disorders: Scoping Review.

Mental stress and its consequent mental health disorders (MDs) constitute a significant public health issue. With the advent of machine learning (ML), there is potential to harness computational techniques for better understanding and addressing mental stress and MDs. This comprehensive review seeks to elucidate the current ML methodologies used in this domain to pave the way for enhanced detection, prediction, and analysis of mental stress and its subsequent MDs. This review aims to investigate the scope of ML methodologies used in the detection, prediction, and analysis of mental stress and its consequent MDs. Using a rigorous scoping review process with PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews) guidelines, this investigation delves into the latest ML algorithms, preprocessing techniques, and data types used in the context of stress and stress-related MDs. A total of 98 peer-reviewed publications were examined for this review. The findings highlight that support vector machine, neural network, and random forest models consistently exhibited superior accuracy and robustness among all ML algorithms examined. Physiological parameters such as heart rate measurements and skin response are prevalently used as stress predictors due to their rich explanatory information concerning stress and stress-related MDs, as well as the relative ease of data acquisition. The application of dimensionality reduction techniques, including mappings, feature selection, filtering, and noise reduction, is frequently observed as a crucial step preceding the training of ML algorithms. The synthesis of this review identified significant research gaps and outlines future directions for the field. These encompass areas such as model interpretability, model personalization, the incorporation of naturalistic settings, and real-time processing capabilities for the detection and prediction of stress and stress-related MDs.

Clemastine improves emotional and social deficits in adolescent social isolation mice by reversing demyelination

Adolescence is a critical period for social experience-dependent oligodendrocyte maturation and myelination. Adolescent stress predisposes to cause irreversible changes in brain structure and function with lasting effects on adulthood or beyond. However, the molecular mechanisms linking adolescent social isolation stress with emotional and social competence remain largely unknown. In our study, we found that social isolation during adolescence leads to anxiety-like behaviors, depression-like behaviors, impaired social memory and altered patterns of social ultrasonic vocalizations in mice. In addition, adolescent social isolation stress induces demyelination in the prefrontal cortex and hippocampus of mice, with decreased myelin-related gene expression and disrupted myelin structure. More importantly, clemastine was sufficient to rescue the impairment of emotional and social memory by promoting remyelination. These findings reveal the demyelination mechanism of emotional and social deficits caused by social isolation stress in adolescence, and provides potential therapeutic targets for treating stress-related mental disorders.

The causal effect of mental health on labor market outcomes: The case of stress-related mental disorders following a human-made disaster

As disasters increase due to climate change, population density, epidemics, and technology, information is needed about postdisaster consequences for people's mental health and how stress-related mental disorders affect multiple spheres of life, including labor-market attachment. We tested the causal hypothesis that individuals who developed stress-related mental disorders as a consequence of their disaster exposure experienced subsequent weak labor-market attachment and poor work-related outcomes. We leveraged a natural experiment in an instrumental variables model, studying a 2004 fireworks factory explosion disaster that precipitated the onset of stress-related disorders (posttraumatic stress disorder, anxiety, and depression) among individuals in the local community (N = 86,726). We measured labor-market outcomes using longitudinal population-level administrative data: sick leave, unemployment benefits, early retirement pension, and income from wages from 2007 to 2010. We found that individuals who developed a stress-related disorder after the disaster were likely to go on sickness benefit, both in the short- and long-term, were likely to use unemployment benefits and to lose wage income in the long term. Stress-related disorders did not increase the likelihood of early retirement. The natural experiment design minimized the possibility that omitted confounders biased these effects of mental health on work outcomes. Addressing the mental health and employment needs of survivors after a traumatic experience may improve their labor-market outcomes and their nations' economic outputs.

Cognitive Training Prevents Stress-Induced Working Memory Deficits

BackgroundWorking memory is a fundamental cognitive process that is critically involved in planning, comprehension, reasoning, and problem solving. Acute stress has been shown to impair working memory. This stress-induced working memory deficit has profound implications for cognitive functioning in everyday life as well as for stress-related mental disorders. Here, we tested whether a cognitive training intervention would make working memory more resistant to disruptive effects of acute stress. MethodsIn a preregistered, fully crossed between-subjects design with the factors stress (vs. control) and cognitive training (vs. sham), 123 healthy men and women (ages 18–35 years) completed a daily cognitive training program targeting working memory–related processes or a sham training over a period of 6 weeks. After this 6-week training intervention, participants underwent a standardized stress or control manipulation shortly before their working memory performance was tested. ResultsAs expected, the exposure to acute stress led to a significant working memory impairment in the sham training group. Critically, although the subjective, autonomic, and endocrine stress responses were comparable in the 2 training groups, this stress-induced working memory impairment was abolished in the intervention training group. ConclusionsThese results are the first to show that a cognitive training intervention directed at prefrontal and hippocampal functioning can prevent the detrimental effects of stressful events on working memory performance.

THE MEDIATING ROLE OF POOR SLEEP QUALITY IN THE RELATIONSHIP BETWEEN POSTTRAUMATIC STRESS DISORDER AND AGGRESSION IN COMBATANTS

Introduction. Stress-related mental disorders pose a significant risk to a patient's social, emotional, and physical well-being. One of the most vulnerable categories of the population to the development of stress-related mental disorders, including post-traumatic stress disorder, in wartime is military personnel who are constantly faced with events that threaten their lives and health. The most common complaints of combatants with PTSD include sleep disturbances and aggression. Therefore, we hypothesized that poor sleep quality may mediate the association between PTSD and aggression in combat veterans. Methods and materials. We conducted a clinical study of 45 combatants, who were divided into the following groups: group 1 (n=24) – combatants with PTSD, and group 2 (n=21) – combatants without stress-related mental disorders. We measured sleep quality by the Pittsburgh Sleep Quality Index and aggression by the Buss-Perry Aggression Questionnaire. Statistical analysis was performed using Jamovi Desktop. The mediation analysis was performed using the medmod 1.1.0 and advanced mediation models 1.0.5. Results. We found a strong statistically significant effect of PTSD on physical aggression (p&lt;0.001). However, the mediating role of sleep was not found (p=0.264), as the effect of sleep disturbance on physical aggression was not confirmed (p=0.257), despite the strong effect of PTSD on sleep disturbance (p&lt;0.001). It was found that the indirect effect of mediation through poor sleep quality accounted for 74.1% of the mediation of the relationship between PTSD and hostility. We established a partial mediation of the relationship between PTSD and aggressiveness by poor sleep quality. The direct effect accounts for 47.6% of the mediation, and the indirect effect through sleep disturbances accounts for 52.4%, which confirms the role of poor sleep quality as a mediator in this model. Concluions. Our findings emphasize that sleep disturbance is a significant symptom of PTSD that can affect other aspects of the disease in combatants. In this study, we demonstrate that poor sleep quality mediates hostility fully and general aggression partially in combatants with PTSD.

Sex-Specific Differences and the Role of Environmental Enrichment in the Expression of Hippocampal CB1 Receptors following Chronic Unpredictable Stress.

Stress-related mental disorders have become increasingly prevalent, thus endangering mental health worldwide. Exploring stress-associated brain alterations is vital for understanding the possible neurobiological mechanisms underlying these changes. Based on existing evidence, the brain endogenous cannabinoid system (ECS) plays a significant role in the stress response, and disruptions in its function are associated with the neurobiology of various stress-related disorders. This study primarily focuses on investigating the impact of chronic unpredictable stress (CUS) on the expression of hippocampal cannabinoid type 1 (CB1) receptors, part of the ECS, in adult male and female Wistar rats. Additionally, it explores whether environmental enrichment (EE) initiated during adolescence could mitigate the CUS-associated alterations in CB1 expression. Wistar rats, shortly after weaning, were placed in either standard housing (SH) or EE conditions for a duration of 10 weeks. On postnatal day 66, specific subgroups of SH or EE animals underwent a 4-week CUS protocol. Western blot (WB) analysis was conducted in the whole hippocampus of the left brain hemisphere to assess total CB1 protein expression, while immunohistochemistry (IHC) was performed on the right hemisphere to estimate the expression of CB1 receptors in certain hippocampal areas (i.e., CA1, CA3 and dentate gyrus-DG). The WB analysis revealed no statistically significant differences in total CB1 protein levels among the groups; however, reduced CB1 expression was found in specific hippocampal sub-regions using IHC. Specifically, CUS significantly decreased CB1 receptor expression in the CA1 and DG of both sexes, whereas in CA3 the CUS-associated decrease was limited to SH males. Interestingly, EE housing proved protective against these reductions. These findings suggest a region and sex-specific endocannabinoid response to chronic stress, emphasizing the role of positive early experiences in the protection of the adolescent brain against adverse conditions later in life.

Regarding the implementation of foreign psychotherapeutic approaches in the mental health protection system of the population of Ukraine in conditions of war

Background. The work is devoted to the problem of preserving the mental health of the population of Ukraine. The emergence of stress-related mental disorders, including post-traumatic stress disorder, leads to a negative effect on families and communities, problems of mutual understanding, support and recovery. Against this background, there is no doubt about the need to implement the experience of Western colleagues in the mental health care system at all levels of care provision. The purpose of the work is to update the issue of the implementation of foreign psychotherapeutic approaches in the system of mental health care of the population of Ukraine in the conditions of war. Materials and methods. On the basis of the analysis of literary sources and information resources, a modern overview of the problem of introducing modern psychotherapeutic directions into the system of mental health protection of the population in wartime conditions was obtained. Discussion. An analytical review of pathogenetic prerequisites for the implementation of the experience of Western doctors in rehabilitation measures and psychological support measures was carried out. Implementation of strategies aimed at preventing mental illness through education, stress reduction, and development of psychosocial support can help reduce the prevalence of risk factors for the development of mental health problems. Justification of the implementation of Western experience is important for improving the provision of assistance in the mental health system in Ukraine, which will meet modern standards and take into account the peculiarities of Ukrainian culture and society.At the same time, ensuring effective rehabilitation for victims is an act of recognition of their dignity and rights to a full life. Conclusions. At the current stage, Western health care systems emphasize the prevention of mental illnesses through education, stress reduction, and the development of psychosocial support. Implementing these strategies can help reduce the prevalence of risk factors for developing mental health problems. The ability to integrate mental health care into the general medical context is a priority, as it can improve detection of mental illness, provide a comprehensive approach to treatment, and reduce stigmatisation in the society. Focusing on the scientific basis is a priority, because the proven base of Western approaches to the issue of maintaining mental health is based on scientific research and effective methods.

A post-traumatic stress disorder in military servicemen and war veterans

Aim. To analyze the characteristics of the incidence of a post-traumatic stress disorder in military servicemen and war veterans in order to search for new methods of diagnosis and treatment. Materials and methods. The analysis of the data of a secret questionnaire of doctors (psychiatrists, neuropathologists) regarding changes in character, complaints about anxiety after returning from the war zone in military servicemen and war veterans was used. Results and discussion. Since the start of russia’s full-scale invasion of Ukraine, there has been a brutal, exhausting war bringing a post-traumatic stress disorder (PTSD) on a par with Ukraine’s leading health problems. By monitoring foreign sources and literature, which more broadly highlight the problems of military personnel and war veterans with experience of working in such harsh conditions, a study on the prevalence of a post-traumatic stress disorder was conducted. Conclusions. Therefore, it is promising to conduct further research to improve understanding of the prevalence of a post-traumatic stress disorder in military servicemen and war veterans, which remains one of the “young” diagnoses in Ukraine and in world psychiatry. In the International Classification of Diseases (ICD-10), it is designated by the code F43. 1 and is included in the section F40-F48 “Anxiety, dissociative, stress-related, somatoform and other nonpsychotic mental disorders”.

Exercise as Treatment for "Stress-Related" Mental Disorders.

The beneficial impact of physical activity on preventing and treating mental disorders has captured growing (research) interest. This article aims to provide a concise overview of essential evidence regarding the effectiveness and underlying mechanisms of physical activity for individuals with mental disorders clustered as "stress-related" conditions. Empirical findings (e.g., longitudinalprospective studies, interventional randomized-controlled-trials, reviews, meta-analyses) regarding the effects of physical activity in the prevention and treatment of stress-related mental disorders are summarized. Furthermore, potential mechanisms underlying these effects are discussed, and recommendations regarding the use of physical activity are outlined. The majority of studies indicate good efficacy of physical activity in prospectively lowering the risk for the incidence of subsequent stress-related mental disorders as well as in the treatment of manifest disorders. Most evidence targets unipolar depressive disorder and, secondly, anxiety disorders. Research regarding posttraumatic stress disorder, obsessive-compulsive disorders, and somatoform disorders is promising but scarce. Physical activity seems to be useful as a stand-alone-treatment as well as in combination with other psychotherapeutic or pharmacological treatments. Multiple intertwined physiological, psychological, and social mechanisms are assumed to mediate the beneficial effects. Recommendations regarding physical activity can orientate on official guidelines but should consider the individual needs and circumstances of each subject. In summary, physical activity seems to be effective in the prevention and treatment of stressrelated mental disorders and, therefore, should be fostered in healthcare-settings. Future studies are needed to clarify partly inconsistent patterns of results and to close research gaps, e.g., concerning somatoform disorders.

Сучасне уявлення про вплив стресу на імунну систему вагітної

Today, there is increasing attention being paid to mental health, especially in pregnant women who are vulnerable to the risk of mental disorders such as depression, anxiety, and post-traumatic stress disorder. Despite scientific progress, research on the impact of stress on mental health during pregnancy is insufficient. Purpose - to analyze the impact of stress on the immune system of pregnant women. A search and analysis of 78 original studies investigating the impact of stress on the course of pregnancy were conducted. Keywords and article selection criteria were applied. The systematic review included the most relevant studies that met the established criteria. The findings indicate that the immune system plays a significant role in the development of stress-related mental disorders during pregnancy. However, most studies do not establish a clear link between stress, inflammation, and mental disorders in pregnant women. Conclusions. The review highlights the need for further research aimed at understanding the relationship between stress, the immune system, and mental health in pregnant women. This will help develop effective methods for the prevention and treatment of mental disorders in this population, promoting healthy pregnancy outcomes and the birth of healthy children. No conflict of interests was declared by the authors.

Beneficial Effects of Acupuncture for Depression-A Possible Mediation of Peripheral Sensory Stimulation and Central Oxytocin Release

In modern society, depression is one of the most common mental disorders. It is generally thought that depression is due to the disorders of neuronal circuits and chemical balance in the brain. Patients with depression often receive treatment with selective serotonin reuptake inhibitors (SSRIs). However, recent studies suggest that the magnitude of benefit of pharmacological treatment is quite limited for these patients. Although recent studies propose acupuncture as a non-pharmacological approach to managing depression, the mechanism of its beneficial effects is not well understood. Somatosensory pathways stimulated by acupuncture relay to the central nervous system (CNS). In animal studies, acupuncture has demonstrated the potential to ameliorate neural abnormalities associated with depression. As complex daily life stress is highly associated with depression, the procedure that suppresses stress responses would be a good candidate to treat depression. Oxytocin (OXT) is a hormone produced at the hypothalamus and mediates social bonding and stress reduction. OXT inhibits stress-induced corticotropin-releasing factor (CRF) expression at the hypothalamus, resulting in anti-stress and anti-anxiety effects. Research has demonstrated that acupuncture stimulates the release of hypothalamic OXT through somatosensory stimulation. Thus, stress-related mental disorders can be treated, at least in part, by acupuncture. It is proposed that somatosensory stimulations induced by acupuncture are a possible candidate as a non-pharmacological approach for depression.

Ventral tegmental area dopaminergic circuits participates in stress-induced chronic postsurgical pain in male mice

BackgroundChronic postsurgical pain (CPP) markedly impairs patients’ quality of life. Research has shown that chronic stress may extend incisional nociception in male mice. Dopaminergic (DAergic) neurons in the ventral tegmental area (VTA) are integral to stress-related mental disorders (including major depressive disorder, anxiety disorders, and PTSD) and pain. However, the impact of chronic social defeat stress (CSDS) on mesolimbic dopamine (DA) transmission in the development of CPP is yet to be established. It remains uncertain whether the dopamine signals in the rostral anterior cingulate cortex (rACC), which regulate pain, derive from the VTA. This study aims to explore the role of VTA-rACC dopaminergic circuits in a mouse model of CPP induced by CSDS.MethodsWe conducted CSDS on C57BL/6 J wild-type male mice (n = 12–16 mice/group) and DAT-cre male mice (n = 10–12 mice/group). After 10 days of CSDS, a left posterior plantar incision was made to establish a mouse model of CPP. Paw withdrawal thresholds (PWTs) were evaluated using Von-Frey fibre stimulation. The open field test (OFT) and elevated plus maze test (EPM) were used to assess pain-related negative emotions. We used immunofluorescence staining and Western Blot to analyse D1, D2, c-Fos, and TH expression. DAergic fibre projections in the VTA-rACC neural pathway were traced using retrograde tracing and immunofluorescence staining. Optogenetics and Chemogenetics were employed to manipulate DAergic neurons in the VTA and their axons in the rACC.ResultsThe ipsilateral PWTs in male C57BL/6 J mice significantly decreased after surgery, returning to baseline after seven days. Conversely, in CSDS mice, ipsilateral PWTs remained reduced for at least 30 days post-incision. A significant reduction in TH-positive neurons expressing c-Fos in the VTA of CPP mice was observed 15 days post-incision. Activating DAergic neurons significantly improved ipsilateral PWTs and locomotor performance in the OFT and EPM in CPP mice post-incision. Additionally, D1 expression in the rACC was found to decrease in CPP mice, and this reduction counteracted the increase in PWTs caused by activating DAergic neuron axon terminals in the rACC.ConclusionCSDS results in chronicity of postsurgical nociception and anxiety-like negative emotions, with alterations in DA transmission playing a role in CPP. Specific activation of DAergic neurons mitigates nociceptive responses and anxiety-like bahaviors, possibly mediated by D1 receptors in the rACC.

The Role of Telomere Length in Stress-related Aging and its Implications for Mental Health

Telomeres, the protective caps at chromosome ends, have emerged as crucial biomarkers of cellular aging and potential mediators of stress-induced physiological decline. This review synthesized current evidence on how chronic stress and various mental health conditions are associated with accelerated telomere shortening, potentially serving as a biological mechanism linking psychological distress to cellular aging and increased risk of age-related diseases. Research studies showed that major depressive disorder, post-traumatic stress disorder, and anxiety disorders have been consistently linked to shorter telomeres, while findings for bipolar disorder and schizophrenia remain mixed. The review explored the biological mechanisms underlying stress-induced telomere attrition, including oxidative stress, inflammation, and dysregulation of the hypothalamic-pituitary-adrenal axis. It critically evaluated telomere length as a potential biomarker for stress-related aging and mental health disorders, assessing its reliability and clinical relevance. The review also examined interventions targeting telomere biology, including lifestyle modifications, stress reduction techniques, and pharmacological approaches. These interventions showed promise in mitigating the effects of stress-related aging and improving mental health outcomes. However, methodological challenges and high inter-individual variability currently limit the clinical utility of telomere length assessment. Ethical implications of telomere-based interventions and diagnostics were also discussed, including issues of privacy, potential discrimination, and the blurring lines between treatment and enhancement.

Multiple Sex- and Circuit-Specific Mechanisms Underlie Exercise-Induced Stress Resistance.

Prior physical activity reduces the risk of future stress-related mental health disorders including depression, anxiety, and post-traumatic stress disorder. Rodents allowed to engage in voluntary wheel running are similarly protected from behavioral consequences of stress. The present review summarizes current knowledge on mechanisms underlying exercise-induced stress resistance. A conceptual framework involving the development (during exercise) and expression (during stress) of stress resistance from exercise is proposed. During the development of stress resistance, adaptations involving multiple exercise signals and molecular mediators occur within neural circuits orchestrating various components of the stress response, which then respond differently to stress during the expression of stress resistance. Recent data indicate that the development and expression of stress resistance from exercise involve multiple independent mechanisms that depend on sex, stressor severity, and behavioral outcome. Recent insight into the role of the prefrontal cortex in exercise-induced stress resistance illustrates these multiple mechanisms. This knowledge has important implications for the design of future experiments aimed at identifying the mechanisms underlying exercise-induced stress resistance.

The utility of wearable headband electroencephalography and pulse photoplethysmography to assess cortical and physiological arousal in individuals with stress-related mental disorders.

Several stress-related mental disorders are characterised by disturbed sleep, but objective sleep biomarkers are not routinely examined in psychiatric patients. We examined the use of wearable-based sleep biomarkers in a psychiatric sample with headband electroencephalography (EEG) including pulse photoplethysmography (PPG), with an additional focus on microstructural elements as especially the shift from low to high frequencies appears relevant for several stress-related mental disorders. We analysed 371 nights of sufficient quality from 83 healthy participants and those with a confirmed stress-related mental disorder (anxiety-affective spectrum). The median value of macrostructural, microstructural (spectral slope fitting), and heart rate variables was calculated across nights and analysed at the individual level (N = 83). The headbands were accepted well by patients and the data quality was sufficient for most nights. The macrostructural analyses revealed trends for significance regarding sleep continuity but not sleep depth variables. The spectral analyses yielded no between-group differences except for a group × age interaction, with the normal age-related decline in the low versus high frequency power ratio flattening in the patient group. The PPG analyses showed that the mean heart rate was higher in the patient group in pre-sleep epochs, a difference that reduced during sleep and dissipated at wakefulness. Wearable devices that record EEG and/or PPG could be used over multiple nights to assess sleep fragmentation, spectral balance, and sympathetic drive throughout the sleep-wake cycle in patients with stress-related mental disorders and healthy controls, although macrostructural and spectral markers did not differ between the two groups.

Advances in electrochemical biosensor design for the detection of the stress biomarker cortisol.

The monitoring of stress levels in humans has become increasingly relevant, given the recent incline of stress-related mental health disorders, lifestyle impacts, and chronic physiological diseases. Long-term exposure to stress can induce anxiety and depression, heart disease, and risky behaviors, such as drug and alcohol abuse. Biomarker molecules can be quantified in biological fluids to study human stress. Cortisol, specifically, is a hormone biomarker produced in the adrenal glands with biofluid concentrations that directly correlate to stress levels in humans. The rapid, real-time detection of cortisol is necessary for stress management and predicting the onset of psychological and physical ailments. Current methods, including mass spectrometry and immunoassays, are effective for sensitive cortisol quantification. However, these techniques provide only single measurements which pose challenges in the continuous monitoring of stress levels. Additionally, these analytical methods often require trained personnel to operate expensive instrumentation. Alternatively, low-cost electrochemical biosensors enable the real-time detection and continuous monitoring of cortisol levels while also providing adequate analytical figures of merit (e.g., sensitivity, selectivity, sensor response times, detection limits, and reproducibility) in a simple design platform. This review discusses the recent developments in electrochemical biosensor design for the detection of cortisol in human biofluids. Special emphasis is given to biosensor recognition elements, including antibodies, molecularly imprinted polymers (MIPs), and aptamers, as critical components of electrochemical biosensors for cortisol detection. Furthermore, the advantages and limiting factors of various electrochemical techniques and sensing in complex biofluid matrices are overviewed. Remarks on the current challenges and future perspectives regarding electrochemical biosensors for stress monitoring are provided, including matrix effects (pH dependence and biological interferences), wearability, and large-scale production.

Dose-dependent action of cordycepin on the microbiome-gut-brain-adipose axis in mice exposed to stress

The high risk for anxiety and depression among individuals with stress has become a growing concern globally. Stress-related mental disorders are often accompanied by symptoms of metabolic dysfunction. Cordycepin is a Chinese herbal medicine commonly used for its metabolism-enhancing effects. We aimed to investigate the dose-dependent effects of cordycepin on psycho-metabolic disorders induced by stress. Our behavioral tests revealed that 12.5 mg/kg cordycepin by oral gavage significantly attenuated the anxiety- and depression-like behaviors induced by stress in mice. At 25 mg/kg, cordycepin restored the reduced weight and cell size of adipose tissues caused by stress. Besides ameliorating the metabolic dysbiosis of gut microbiota due to stress, cordycepin significantly reduced the elevated contents of 5-hydroxyindoleacetic acid in the serum and prefrontal cortex at 12.5 mg/kg and reversed the decrease in adipose induced by stress at 25 mg/kg. Correlation analyses further revealed that 12.5 mg/kg cordycepin reversed stress-induced changes in the intestinal microbiome of NK4A214_group and decreased serum Myristic acid and PC(15:0/18:1(11Z)) and cytokines, such as IFN-γ and IL-1β. 25 mg/kg cordycepin reversed stress-induced changes in the abundances of Prevoteaceae_UCG-001 and Desulfovibrio, increased serum L-alanine level, and decreased serum Inosine-5'-monophosphate level. Cordycepin thereby ameliorated the anxiety- and depression-like behaviors as well as disturbances in the adipose metabolism of mice exposed to stress. Overall, these findings offer evidence indicating that the prominent effects of cordycepin in the brain and adipose tissues are dose dependent, thus highlight the importance of evaluating the precise therapeutic effects of different cordycepin doses on psycho-metabolic diseases.

Detecting Prolonged Stress in Real Life Using Wearable Biosensors and Ecological Momentary Assessments: Naturalistic Experimental Study.

Increasing efforts toward the prevention of stress-related mental disorders have created a need for unobtrusive real-life monitoring of stress-related symptoms. Wearable devices have emerged as a possible solution to aid in this process, but their use in real-life stress detection has not been systematically investigated. We aimed to determine the utility of ecological momentary assessments (EMA) and physiological arousal measured through wearable devices in detecting ecologically relevant stress states. Using EMA combined with wearable biosensors for ecological physiological assessments (EPA), we investigated the impact of an ecological stressor (ie, a high-stakes examination week) on physiological arousal and affect compared to a control week without examinations in first-year medical and biomedical science students (51/83, 61.4% female). We first used generalized linear mixed-effects models with maximal fitting approaches to investigate the impact of examination periods on subjective stress exposure, mood, and physiological arousal. We then used machine learning models to investigate whether we could use EMA, wearable biosensors, or the combination of both to classify momentary data (ie, beeps) as belonging to examination or control weeks. We tested both individualized models using a leave-one-beep-out approach and group-based models using a leave-one-subject-out approach. During stressful high-stakes examination (versus control) weeks, participants reported increased negative affect and decreased positive affect. Intriguingly, physiological arousal decreased on average during the examination week. Time-resolved analyses revealed peaks in physiological arousal associated with both momentary self-reported stress exposure and self-reported positive affect. Mediation models revealed that the decreased physiological arousal in the examination week was mediated by lower positive affect during the same period. We then used machine learning to show that while individualized EMA outperformed EPA in its ability to classify beeps as originating from examinations or from control weeks (1603/4793, 33.45% and 1648/4565, 36.11% error rates, respectively), a combination of EMA and EPA yields optimal classification (1363/4565, 29.87% error rate). Finally, when comparing individualized models to group-based models, we found that the individualized models significantly outperformed the group-based models across all 3 inputs (EMA, EPA, and the combination). This study underscores the potential of wearable biosensors for stress-related mental health monitoring. However, it emphasizes the necessity of psychological context in interpreting physiological arousal captured by these devices, as arousal can be related to both positive and negative contexts. Moreover, our findings support a personalized approach in which momentary stress is optimally detected when referenced against an individual's own data.