Does the stress axis mediate behavioural flexibility in a social cichlid, Neolamprologus pulcher?

Behavioural flexibility plays a major role in the way animals cope with novel situations, and physiological stress responses are adaptive and highly efficient mechanisms to cope with unpredictable events. Previous studies investigating the role of stress responses in mediating behavioural flexibility were mostly done in laboratory rodents using stressors and cognitive challenges unrelated to the ecology of the species. To better understand how stress mediates behavioural flexibility in a natural context, direct manipulations of the stress response and cognitive tests in ecologically relevant contexts are needed. To this aim, we pharmacologically blocked glucocorticoid receptors (GR) in adult Neolamprologus pulcher using a minimally invasive application of a GR antagonist. GR blockade prevents the recovery after a stressful event, which we predicted to impair behavioural flexibility. After the application of the GR antagonist, we repeatedly exposed fish to a predator and tested their behavioural flexibility using a detour task, i.e. fish had to find a new, longer route to the shelter when the shortest route was blocked. While the latencies to find the shelter were not different between treatments, GR blocked fish showed more failed attempts during the detour tasks than control fish. Furthermore, weak performance during the detour tasks was accompanied by an increase of fear related behaviours. This suggests that blocking GR changed the perception of fear and resulted in an impaired behavioural flexibility. Therefore, our results support a potential link between the capacity to recover from stressors and behavioural flexibility in N. pulcher with potential consequences for an effective and adaptive coping with changing environments.

The dexamethasone suppression test as a biomarker for suicidal behavior: A systematic review and meta-analysis.

BACKGROUND: The dexamethasone suppression test (DST), which measures HPA-axis functioning, is a potential biomarker for suicidal behavior. The current study aimed (a) to synthesize available knowledge on the association between DST non-suppression and suicidal behavior, and (b) to study potential moderators. METHODS: A total of 4236 studies were screened, 43 were included. Suicide attempts and suicide completion were studied separately. The meta-analysis included 37 effect sizes for suicide attempts (n = 3733) and 11 effect sizes for suicide completion (n = 1626). RESULTS: DST non-suppression was associated with completed suicide (odds ratio (OR) = 2.10, (95 % CI [1.37, 3.23]). For suicide attempts, we found no evidence that DST status was associated in the overall meta-analysis including all patient samples. However, moderator analysis indicated that the DST status was associated with suicide attempts in patient samples that included psychopathology other than just mood disorders, such as psychotic, substance use and personality disorders (OR = 2.34, 95 % CI [1.39-3.93], k = 11). LIMITATIONS: The potential influence of publication bias and exclusion of some relevant published studies (since effect sizes could not be calculated, authors could not supply data or authors could not be reached) are limitations. Furthermore, missing moderator data decreased our ability to explain heterogeneity between studies. CONCLUSIONS: The results of this meta-analysis support the hypothesis that DST non-suppression is predictive of suicidal behavior. More research is needed to investigate optimal cut-off values, confounding factors and the potential usefulness of the DST in clinical practice in terms of personalized medicine.

Links between ethnic discrimination, mental health, protective factors, and hair cortisol concentrations in asylum seekers living in Germany.

Objective: Asylum seekers often experience ethnic discrimination on the flight or in the host country, which may be associated with chronic stress and impaired mental health. Dysregulation of the hypothalamic-pituitary-adrenal axis, a known physiological correlate of chronic stress, can be assessed using hair cortisol concentrations (HCC). The present study aimed to investigate how different forms of perceived ethnic discrimination are associated with mental health outcomes, HCC, and protective factors in asylum seekers living in Germany.Methods: Somatic symptoms (PHQ-15), symptoms of posttraumatic stress (PDS), depressive symptoms (PHQ-9), different forms of ethnic discrimination (active harm, passive harm, institutional discrimination), and protective factors (in-group identification, social support) were assessed cross-sectionally in 144 asylum seekers (average age 32 years, average duration of stay in Germany nine months; 67% men). HCC were obtained from 68 participants. Multiple regression analyses were conducted and social support and in-group identification were tested as potential moderators.Results: Active ethnic discrimination was positively associated with all assessed mental health outcomes, and all forms of ethnic discrimination positively correlated with depressive symptoms. Ethnic discrimination was not associated with HCC. When controlling for other possible influences (e.g. age, gender, traumatic events), passive harm was negatively associated with depressive symptoms (ß = -0.17, p = .033) and active harm was positively associated (ß = 0.28, p = .022) with somatic symptoms. After the inclusion of the protective factors, the associations were no longer significant. Lower social support was associated with higher depressive symptoms (ß = -0.35, p < .001), posttraumatic stress (ß = -0.77, p < .001), and somatic symptoms (ß = -0.32, p < .001), but did not moderate the associations between ethnic discrimination and the mental health outcomes.Conclusions: Perceived ethnic discrimination may negatively influence asylum seekers' mental health but does not seem to be associated with HCC. Social support was associated with psychological symptom severity, but did not buffer the effects of ethnic discrimination on mental health.

The study examined the relationship between ethnic and institutional discrimination, protective factors (social support and in-group identification), hair cortisol concentrations (HCC) and mental health in asylum seekers.Ethnic discrimination was associated with mental health outcomes and social support, but not with HCC.Lower social support was associated with higher depressive and somatic symptoms, but did not moderate the relationship between ethnic discrimination and mental health.

Hair cortisol concentrations in clipped and combed hair and associations with characteristics, health status and stress in domestic cats.

Hair cortisol concentrations (HCC) are measured to assess long-term HPA-axis activity and may represent a valuable non-invasive tool to evaluate chronic stress in cats. This study investigated combing as a novel, low-stress method for HCC assessment, as well as possible associations between HCC and cat characteristics in 167 owned cats. Hair was sampled at veterinary clinics through clipping and/or combing the cat, or at home by the owner combing the cat. A questionnaire was sent to cat owners, including inquiries about the cat's sex, health status, and exposure to stress. HCC was quantified using a commercial cortisol assay kit. Despite variations within and between sampling methods, Spearman's correlation and Bland-Altman plots revealed a moderate correlation between clipped and combed samples (rs = 0.61, LOA -5.51 ± 22.54). In multiple linear regression, variations in HCC were observed based on sex, health status and cat group size. No associations were found between HCC and stress as assessed by owners. Despite study limitations and remaining uncertainty regarding factors influencing HCC, combing presents a convenient approach for evaluating long-term HPA-axis activity in clinical settings. The association between health and HCC suggests alterations in cortisol levels that are related to disease processes and stress-inducing events associated with the disease.

Association of stress hormones and the risk of cardiovascular diseases systematic review and meta-analysis.

Background: The roles of endogenous stress hormones (norepinephrine, epinephrine, and cortisol) in cardiovascular diseases have been discussed. However, the higher versus lower level of stress hormones in relation to cardiovascular risks remained uncertain. Methods: We searched databases from their inception to 31, March 2023. We conducted a meta-analysis to estimate the effect of higher to lower level of stress hormones with random effect model. Subgroup and meta-regression analysis were done to clarify the heterogeneity. Results: In total, 33 studies involving 43641 participants were included. With regard to cardiovascular disease risks, a higher risk for individuals with higher level of all stress hormones (risk ratio (RR), 1.63; 95 % Confidence intervals (CIs): 1.36, 1.97) was noted compared with lower level of all stress hormones. The meta-regression showed that as the follow-up year increased per year, the impact of higher level of all stress hormones on the risk of cardiovascular disease declined significantly (RR, -0.09; 95 % CIs: 0.15, -0.03, p = 0.006). A significantly higher risk of cardiovascular diseases for individuals with higher level of norepinephrine (RR, 1.68; 95 % CIs: 1.37, 2.06), with higher level of epinephrine (RR, 1.58; 95 % CIs: 1.10, 2.26), and with higher level of cortisol (RR, 1.60; 95 % CIs: 1.04, 2.26) were noted compared with a lower level of each stress hormone. Conclusion: Higher levels of stress hormones were significantly associated with higher risks of cardiovascular diseases compared with lower levels of stress hormones.

Diurnal cortisol patterns in chronic pain: Associations with work-family spillover, work, and home stress.

Chronic pain is a prevalent condition with significant impacts on individuals' lives, including heightened stress and impaired physiological functioning. Given that work and family are the two main social domains where stress manifests, this study aimed to investigate the interactions between chronic pain, work-family stressors, and diurnal cortisol patterns to understand how chronic pain affects daily life and physiological stress responses. We identified 1,413 adults with chronic pain and 1,413 matched controls within MIDUS II samples to examine work-family spillover, daily work and home stressors, and cortisol levels across multiple days. The chronic pain group reported more negative work to family spillover and experienced more instances of stressful home events, particularly avoided arguments. These results align with literature suggesting chronic pain exacerbates tensions in close relationships and increases stress. The chronic pain group also had higher cortisol levels cross late-day periods, indicative of hypothalamic-pituitary-adrenal (HPA) axis dysregulation. This dysregulation is associated with poorer health outcomes, including increased inflammation and psychological distress. We did not find any differences in previously identified cortisol profiles, which are higher-level summaries of cortisol levels within each day. We discuss why such difference might not have appeared in this sample.

Postmortem study of adrenomedullin and cortisol in femoral serum and pericardial fluid related to acute pulmonary edema.

Currently, various tools aid in determining the cause of death and the circumstances surrounding it. Thanatochemistry is one such method that provides insights into the physiopathological mechanisms of death and the behavior of specific biomarkers in different body fluids postmortem. Certain biomarkers, characterized by their stability and specificity to vital tissues like the lungs, are associated with mechanisms contributing to death, such as acute pulmonary edema (APE). This study aims to analyze the behavior of midregional pro-adrenomedullin (MR-proADM) and cortisol levels, measured in pericardial fluid and femoral serum, in relation to the severity of APE, categorized according to specific criteria. Samples were collected from a total of 92 corpses (77 males, 15 females) with a mean age of 56.7 ± 15.2 years. The severity of APE associated with the deaths was classified into three groups: slight or absent (n = 7; 8.6%), medium or moderate (n = 16; 19.8%), and intense (n = 58;71.6%).The determination of MR-proADM and cortisol levels was conducted using ELISA kits and an Immunoassay Analyzer, respectively. Our results reveal a significant increase in MR-proADM concentration with the severity of APE. Furthermore, a correlation was established between cortisol and MR-proADM concentrations in both pericardial fluid and femoral serum samples. This indicates that the severity of APE influences the production of ADM, regardless of the specific underlying pathophysiological mechanisms. Cortisol values were also found to be higher in the intense APE group compared to the moderate group.This study contributes to our understanding of the relationship between MR-proADM and cortisol, and the severity of APE, shedding light on potential applications in postmortem investigations.

Hair cortisol and psychiatric symptomatology in children; outcomes of group CBT.

The associations between hair cortisol concentration (HCC), a biomarker of chronic stress, and behavior and sleep disturbance symptoms have not been studied in children with psychiatric disorders. While cognitive behavioral therapy (CBT) has proven effective in treating psychiatric symptoms in children, its potential biological implications as determined by HCC have not been investigated. We explored associations between HCC, behavior and sleep disturbance symptoms, and different diagnostic groupings (depression/anxiety, ADHD, or other types of psychiatric disorders) in clinician-diagnosed 6-12-year-old children (n = 100) with mixed psychiatric disorders and comorbidities. In addition, we examined whether group CBT led to changes in HCC, behavior symptoms, and sleep disturbance symptoms and whether any fluctuations in HCC levels were associated with potential symptom change. We collected data on HCC, internalizing and externalizing symptoms (The Spence Children's Anxiety Self-Report, Child Behavior Checklist, and Teacher Report Form), and sleep disturbance symptoms (The Sleep Disturbance Scale for Children) at three time points (baseline, post-treatment, and seven-month follow-up). Baseline HCC was not associated with behavior or sleep disturbance symptoms, whereas behavior and sleep disturbance symptoms were mutually correlated. No changes in HCC levels were observed with group CBT. Moreover, potential variations in HCC levels over the course of the study did not appear to be associated with behavior symptom relief after group CBT. Our findings suggest that HCC may not be a methodologically relevant biomarker of behavior or sleep disturbance symptoms in children with diverse psychiatric disorders.

Environmental study and stress-related biomarkers modifications in a crew during analog astronaut mission EMMPOL 6.

PURPOSE: Human presence in space is increasingly frequent, but we must not forget that it is a hostile environment. We aimed to study the characteristics of experimental scenarios, to obtain data on human response to isolation, disruption of circadian rhythm and high levels of psychophysical stress. METHODS: In these experiments, we evaluated stress response in five young healthy subjects inside an earth-based moon-settlement-like habitat during a 1-week long analog astronaut mission. Wearable devices were used to monitor daily step count of the subjects, physical activity, heart rate during physical exercise and at rest, and sleep parameters. From saliva and urine samples collected every day at awakening, we studied oxy-inflammation biomarkers and hormones (stress and appetite) were studied too. RESULTS: At the end of the week, all subjects revealed an increase in oxidative stress and cortisol levels but no inflammation biomarkers variations, in conjunction with increasing time/daily exercise. Furthermore, a significant decrease in hours of sleep/day, sleep quality, and REM phase of sleep was recorded and correlated with the increase of reactive oxygen species. CONCLUSION: Oxidative stress increased in a short period of time and may be attributed to the influence of psychological stress during confinement, as well as increased exercise and decreased amount of sleep. On a long-term basis, this could impact performance.

Impact of cortisol on liver fat and metabolic health in adrenal incidentalomas and Cushing's syndrome.

OBJECTIVE: To evaluate liver fat content in patients with non-functional adrenal incidentalomas (NFAI), mild autonomous cortisol secretion (MACS), and Cushing's syndrome (CS), and assess its relationship with cortisol levels. METHODS: This cross-sectional study used retrospective data from 103 NFAI patients, 100 MACS (serum cortisol after a 1-mg dexamethasone test >50 nmol/L), and 59 with CS. Abdominal CT scans measured hepatic and splenic CT values to calculate the liver-to-spleen (L/S) ratio. Metabolic indicators including fasting plasma glucose (FPG), LDL-c, HDL-c, HbA1c, etc were measured. Mediation analysis was used to explore the indirect effects of metabolic traits on the cortisol-liver fat relationship. RESULTS: Patients included 103 NFAI, 100 MACS, and 59 CS. MACS patients had higher NAFLD prevalence (57%) than NFAI (26.2%, p < 0.001) but lower than CS (66.1%, p < 0.001). MACS and CS were associated with NAFLD (OR 3.83 and OR 5.73, p < 0.01), adjusted for age, body mass index (BMI), and covariates. Midnight serum cortisol correlated with L/S ratio (p < 0.001). HbA1c and Triglyceride-glucose index (TyG) mediated 24.5% and 49.5% of the cortisol and L/S ratio association, respectively. FPG, HbA1c, HDL-c, and TyG mediated the association between MACS or CS and the L/S ratio. Homeostasis model assessment of insulin resistance (HOMA-IR), fructosamine, and triglycerides mediated for MACS, while alkaline phosphatase did so for CS. Total cholesterol, LDL-c, ALT, AST, γ-GT, insulin, and uric acid did not mediate the association. CONCLUSION: MACS and CS are linked to significant metabolic disturbances, including increased liver fat and impaired glucose and lipid metabolism, contributing to fatty liver.

Critical illness-related corticosteroid insufficiency: latest pathophysiology and management guidelines.

Intensive care unit (ICU) admissions in the United States exceed 5.7 million annually, often leading to complications such as post-intensive care syndrome and high mortality rates. Among these challenges, critical illness-related corticosteroid insufficiency (CIRCI) requires emphasis due to its complex, multiple-cause pathophysiology and varied presentations. CIRCI, characterized by adrenal insufficiency during critical illness, presents in up to 30% of ICU patients and may manifest as an exaggerated inflammatory response. Factors such as dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, altered cortisol metabolism, tissue corticosteroid resistance, and drug-induced suppression contribute to CIRCI. Diagnosis is a complex process, relying on a comprehensive assessment including clinical presentation, laboratory findings, and dynamic stimulatory testing. Treatment involves intensive medical care and exacting glucocorticoid therapy. Recent guidelines advocate for individualized approaches tailored to patient presentation and etiology. Understanding the pathophysiology and treatment of CIRCI is vital for clinicians managing critically ill patients and striving to improve outcomes. This research paper aims to explore the latest developments in the pathophysiology and management of CIRCI.

Shoden promotes Relief from stress and anxiety: A randomized, double-blind, placebo-controlled study on healthy subjects with high stress levels.

Background: This randomized placebo-controlled study examined the effect of ashwagandha root and leaf extract 60 mg (AE60) and 120 mg (AE120) (35 % withanolide glycosides, Shoden) in physically healthy subjects with higher stress and anxiety. It is hypothesized that a low dose extract with higher withanolide glycosides would decrease cortisol and increase testosterone thereby reducing stress and anxiety. Methods: This parallel arm study recruited 60 subjects with an allocation ratio of 1:1:1 (AE60:AE120: placebo) for 60 days. Subjects who fulfilled the DSM -IV Criteria for generalized anxiety disorder (GAD) with a Hamilton Anxiety Rating Scale, HAMA score >20, and morning serum cortisol >25 mcg/dl were included in the study. The participants did not have depression symptoms and were screened using Montgomery-Asberg Depression Rating Scale. The primary outcome measure was HAMA and the secondary measures were morning serum cortisol, testosterone, perceived stress scale (PSS), clinical global impressions scale (CGI), and patient's global impression of change scale (PGIC). Results: After 60 days, significant differences were observed between the treatment groups and placebo. HAMA scores decreased by 59 % in both AE60 and AE120 groups compared to a negligible increase of 0.83 % in the placebo group (p < 0.0001). Morning serum cortisol levels decreased by 66 % in AE60 and 67 % in AE120, compared to a 2.22 % change in the placebo group (p < 0.0001). Testosterone levels increased by 22 % in AE60 and 33 % in AE120, compared to a 4 % increase in males in the placebo group (p < 0.0001). PSS scores decreased by 53 % in AE60 and 62 % in AE120, CGI-severity scores decreased by 72 % in AE60 and 68 % in AE120, and PGIC scores improved by 60 % in both AE60 and AE120 groups, all showing significant differences compared to the placebo group. Conclusion: Ashwagandha extract with 35 % withanolide glycosides (Shoden) at 60 mg and 120 mg was significantly effective in reduced morning serum cortisol and increasing total testosterone. Therefore, it can be recommended for reducing high stress and anxiety. Clinical trial registration: The study was prospectively registered in Clinical Trial Registry, India with registration number CTRI/2022/04/042133 [Registered on: April 25, 2022].

Effects of simulated space conditions on CD4+ T cells: a multi modal analysis.

Introduction: The immune system is an intricate network of cellular components that safeguards against pathogens and aberrant cells, with CD4+ T cells playing a central role in this process. Human space travel presents unique health challenges, such as heavy ion ionizing radiation, microgravity, and psychological stress, which can collectively impede immune function. The aim of this research was to examine the consequences of simulated space stressors on CD4+ T cell activation, cytokine production, and gene expression. Methods: CD4+ T cells were obtained from healthy individuals and subjected to Fe ion particle radiation, Photon irradiation, simulated microgravity, and hydrocortisone, either individually or in different combinations. Cytokine levels for Th1 and Th2 cells were determined using multiplex Luminex assays, and RNA sequencing was used to investigate gene expression patterns and identify essential genes and pathways impacted by these stressors. Results: Simulated microgravity exposure resulted in an apparent Th1 to Th2 shift, evidenced on the level of cytokine secretion as well as altered gene expression. RNA sequencing analysis showed that several gene pathways were altered, particularly in response to Fe ions irradiation and simulated microgravity exposures. Individually, each space stressor caused differential gene expression, while the combination of stressors revealed complex interactions. Discussion: The research findings underscore the substantial influence of the space exposome on immune function, particularly in the regulation of T cell responses. Future work should focus expanding the limited knowledge in this field. Comprehending these modifications will be essential for devising effective strategies to safeguard the health of astronauts during extended space missions. Conclusion: The effects of simulated space stressors on CD4+ T cell function are substantial, implying that space travel poses a potential threat to immune health. Additional research is necessary to investigate the intricate relationship between space stressors and to develop effective countermeasures to mitigate these consequences.

Evaluation of stress in farmed Atlantic salmon (Salmo salar) using different biological matrices.

Atlantic salmon were subjected to an acute crowding scenario, and their subsequent stress responses were observed under three distinct swimming speed/water flow (WF) conditions: 0.5, 1, and 1.5 body lengths per second (BL/s). Feces, dermal mucus, and plasma were collected for analysis at 1, 6, and 24 h (h) post-stress. Additionally, the head kidney and two regions of the brain (pituitary and POA) were collected for transcript expression analysis. Fish swimming at 0.5 BL/s exhibited higher pre-stress (baseline) cortisol levels. Across all groups and matrices, the highest cortisol/cortisol metabolites (CM) levels were observed at the 1 h post-stress sampling point. At 6 h (second sampling time point), a clear decline toward baseline levels were observe in all groups. Significant increases in mean plasma glucose levels were observed at 1 h post-stress for all groups. The mean plasma lactate levels varied based on WF treatments, with a significant increase observed at 1 h only for the 1.5 BL/s group. Additionally, significant decreases in mean plasma lactate were noted at 6 and 24 h post-stress for some groups. The mRNA abundances of the tested genes (star, cyp17a1, hsd11ß2, srd5a1) increased following the stress events. These changes were not uniform across all groups and were tissue dependent. In summary, the results indicate that mucus and feces can be used as potentially less invasive matrices than blood for evaluating stress and, consequently, the welfare of Atlantic salmon in captivity.

The impact of maternal vulnerability on stress biomarkers and first-trimester growth: the Rotterdam Periconceptional Cohort (Predict Study).

STUDY QUESTION: Is the degree of maternal vulnerability positively associated with stress biomarkers (stress hormones, C-reactive protein, tryptophan metabolites, and one-carbon metabolites), and does long-term exposure to stress hormones reduce first-trimester growth? SUMMARY ANSWER: The maternal vulnerability risk score is positively associated with concentrations of hair cortisol and cortisone and negatively with tryptophan, while higher hair cortisol concentrations are associated with reduced first-trimester growth without mediation of tryptophan. WHAT IS KNOWN ALREADY: A high degree of maternal vulnerability during the periconception period is associated with impaired first-trimester growth and pregnancy complications, with consequences for long-term health of the child and future life course. However, due to the challenges of early identification of vulnerable women, the uptake of periconception care is low in this target group. STUDY DESIGN, SIZE, DURATION: Between June 2022 and June 2023, this study was conducted in a sub-cohort of 160 pregnant women participating in the Rotterdam Periconceptional Cohort (Predict Study), an ongoing prospective tertiary hospital-based cohort. PARTICIPANTS/MATERIALS, SETTING, METHODS: One hundred and thirty-two women with ongoing pregnancies and available stress biomarker data were included in the analysis. Data on periconceptional social, lifestyle, and medical risk factors were collected via self-administered questionnaires, and these factors were used for the development of a composite maternal vulnerability risk score. Stress biomarkers, including stress hormones (hair cortisol and cortisone) and inflammatory and oxidative stress biomarkers (C-reactive protein, total homocysteine, and tryptophan metabolites) were determined in the first trimester of pregnancy. First-trimester growth was assessed by crown-rump length (CRL) and embryonic volume (EV) measurements at 7, 9, and 11 weeks gestation by making use of an artificial intelligence algorithm and virtual reality techniques using 3D ultrasound data sets. The associations between the maternal vulnerability risk score and stress biomarkers were identified using linear regression models, and between stress hormones and CRL- and EV-trajectories using mixed models. A mediation analysis was performed to assess the contribution of tryptophan. All associations were adjusted for potential confounders, which were identified using a data-driven approach. Several sensitivity analyses were performed to check the robustness of the findings. MAIN RESULTS AND THE ROLE OF CHANCE: The maternal vulnerability risk score was positively associated with concentrations of hair cortisol and cortisone (pg/mg) (ß = 0.366, 95% CI = 0.010-0.722; ß = 0.897, 95% CI = 0.102-1.691, respectively), and negatively with tryptophan concentrations (µmol/L) (ß = -1.637, 95% CI = -2.693 to -0.582). No associations revealed for C-reactive protein and total homocysteine. Higher hair cortisol concentrations were associated with reduced EV-trajectories (3√EV: ß = -0.010, 95% CI = -0.017 to -0.002), while no associations were found with CRL-trajectories. Mediation by tryptophan was not shown. LIMITATIONS, REASONS FOR CAUTION: Residual confounding cannot be ruled out, and the external validity may be limited due to the study's single-center observational design in a tertiary hospital. WIDER IMPLICATIONS OF THE FINDINGS: There is mounting evidence that a high degree of maternal vulnerability negatively affects maternal and perinatal health, and that of the future life course. The results of our study emphasize the need to identify highly vulnerable women as early as possible, at least before conception. Our findings suggest that the chronic stress response and alterations of the maternal tryptophan metabolism are involved in maternal vulnerability, affecting first-trimester growth, with potential impact on the long-term health of the offspring. STUDY FUNDING/COMPETING INTEREST(S): This study was funded by the Departments of Obstetrics and Gynecology and Clinical Chemistry of the Erasmus MC, University Medical Center, Rotterdam, the Netherlands, and the Junior Award granted by the De Snoo-van 't Hoogerhuijs Foundation in March 2022. There are no conflicts of interest. TRIAL REGISTRATION NUMBER: N/A.

Exploring the associations between momentary cortisol levels and psychotic-like experiences in young adults: Results from a temporal network analysis of daily-life data.

Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis has been implicated in the development of psychosis and subthreshold psychotic symptoms commonly referred to as psychotic-like experiences (PLEs). The exact mechanisms linking the HPA axis responses with the emergence of PLEs remain unknown. The present study aimed to explore real-life associations between stress, negative affect, salivary cortisol levels (a proxy of the HPA axis activity) as well as PLEs together with their underlying cognitive biases (i.e., threat anticipation and aberrant salience). The study was based on the experience sampling method scheduled over 7 consecutive days in the sample of 77 drug-naïve, young adults (18-35 years). The saliva samples were collected with each prompt to measure cortisol levels. A temporal network analysis was used to explore the directed associations of tested variables. Altogether, 3234 data entries were analyzed. Data analysis revealed that salivary cortisol levels did not directly predict next-moment fluctuations of PLEs. However, higher salivary cortisol levels were associated with higher next-moment levels of PLEs through the effects on threat anticipation and negative affect. In turn, PLEs appeared to predict cortisol levels through the effects on negative affect and event-related stress. Negative affect and threat anticipation were the most central nodes in the network. There might be bidirectional associations between the HPA axis responses and PLEs. Threat anticipation and negative affect might be the most important mediators of these associations. Interventions targeting these mediators might hold promise for disrupting the connection between the HPA axis dysregulation and PLEs.

The curious case of the hypothalamic-pituitary-gonadal axis dysfunction in subordinate female naked mole-rats (Heterocephalus glaber): No apparent role of opioids and glucocorticoids.

The naked mole-rat (Heterocephalus glaber) is a unique model mammal in which to study socially induced inhibition of the hypothalamic-pituitary-gonadal (HPG) axis. Naked mole-rat groups exhibit a high degree of reproductive bias in which breeding is restricted to one female (the queen) and one male, with subordinate non-breeding colony members rarely, if ever, having the opportunity to reproduce due to a dysfunctional HPG axis. It is posited that aggression directed at subordinates by the queen suppresses reproduction in these subordinates, yet the underlying physiological mechanisms causing this dysfunction are unknown. This study aimed to investigate the possible factors contributing to the dysfunction of the HPG axis in subordinate female naked mole-rats with a specific focus on the role of ovarian feedback and stress-related factors such as circulating glucocorticoid and endogenous opioid peptides. The results showed that stress-related factors appear to not mediate the suppression of reproductive function in subordinate female naked mole rats. Indeed, in some cases, the activation of the stress axis may lead to reproductive activation instead of deactivation. At the same time, the role of ovarian sex steroid feedback in reproductive suppression is likely limited and not clearly delineated. This study highlights the need for detailed studies to elucidate the mechanism of reproductive suppression in this unique model mammalian species which may shed light on, and reveal novel mechanisms, in the social regulation of reproduction.

Characteristics of the oral microbiome in youth exposed to caregiving adversity.

Caregiving adversity (CA) exposure is robustly linked to increased risk for poor oral, physical, and mental health outcomes. Increasingly, the gut microbiome has garnered interest as a contributor to risk for and resilience to such health outcomes in CA-exposed individuals. Though often overlooked, the oral microbiome of CA-exposed individuals may be just as important a contributor to health outcomes as the gut microbiome. Indeed, outside the context of CA, the oral microbiome is well-documented as a regulator of both oral and systemic health, and preliminary data suggest its association with mental health. However, research examining the association between CA and the oral microbiome is extremely sparse, especially in childhood, when the community composition of such organisms is still stabilizing. To address that sparsity, in the current study, we examined composition and differential abundance metrics of the oral microbiome in 152 youth aged 6-16 years, who had either been exposed to significant caregiving adversity (significant separation from or maltreatment by a caregiver; N = 66, CA) or who had always remained with their biological/birth families (N = 86, Comparison). We identified a significant negative association between hair cortisol and oral microbiome richness in the Comparison group that was significantly blunted in the CA group. Additionally, youth in the CA group had altered oral microbiome composition and elevated abundance of potentially pathogenic bacteria relative to youth in the Comparison group. Questionnaire measures of fatigue, somatic complaints, and internalizing symptoms had limited associations with oral microbiome features that were altered in CA. Although we found differences in the oral microbiomes of CA-exposed youth, further research is required to elucidate the implications of those differences for health and well-being.

Exploring the Relationship Between Stress, Salivary C-Reactive Protein, and Embodied Physiological Responses in a Nigerian Population.

OBJECTIVES: The impacts of stress on inflammation, although hypothesized, have not been thoroughly examined, especially in relation to social and environmental factors and particularly within Black populations. This study aims to explore the biological mechanisms of embodiment linking stress and health to understand physiological changes in the body's response to psychological stress in a Nigerian population. Through a multidisciplinary approach, this study queries the relationship between stress, cortisol, and salivary C-reactive protein (sCRP), a biomarker of inflammation, while also validating the use of sCRP as a potential and accurate stress indicator in the field. METHODS: In this cross-sectional study, 138 passive drool saliva samples (nfemale = 89 nmale = 49) were collected and assessed for sCRP and cortisol levels in adults. Participants also completed a short demographic survey and, to measure psychological stress, the General Health Questionnaire 12 (GHQ-12). Relationships between sCRP and stress-related variables (i.e., cortisol, GHQ-12, and demographic data) were assessed using Spearman's correlations, simple regression, multivariable linear regression, and exploratory factor analysis. RESULTS: sCRP levels ranged from 20.57 to 6879.41 pg/mL across all samples, with significant differences between female and male participants. The GHQ-12 was not a significant predictor of sCRP variability. However, socio-demographic factors such as body mass index (BMI), age, self-reported sex, ethnic identity, and cortisol were significant predictors, collectively explaining 24%-27% of the variation in sCRP. CONCLUSION: Socio-demographic predictors like BMI, age, sex, and particularly ethnic group experience in Nigeria encapsulate aspects of embodied stress, that significantly affect sCRP variability.

Cushing's syndrome developing myasthenia gravis with takotsubo cardiomyopathy after adrenalectomy: a case report.

BACKGROUND: Several cases of autoimmune disease onset after treatment for Cushing's syndrome have been reported. CASE PRESENTATION: Herein, we report a case of myasthenia gravis crisis in a 51-year-old woman 2 months after adrenalectomy for adrenal Cushing's syndrome accompanied by takotsubo cardiomyopathy. The resolution of excessive endogenous cortisol after adrenalectomy may have triggered the onset of previously latent myasthenia gravis. CONCLUSIONS: Observing the similarities in symptoms between myasthenia gravis and adrenal crisis, which can sometimes be challenging to differentiate, is essential. Moreover, the presence of takotsubo cardiomyopathy as a non-motor manifestation of myasthenic crisis must be noted.