The glucocorticoid receptor (GR) is a critical nuclear receptor that regulates gene expression in diverse tissues, including the heart, where it plays a key role in maintaining cardiovascular health. GR signaling influences essential processes within cardiomyocytes, including hypertrophy, calcium handling, and metabolic balance, all of which are vital for proper cardiac function. Dysregulation of GR activity has been implicated in various cardiovascular diseases (CVDs), highlighting the potential of GR as a therapeutic target. Remarkably, recent insights into GR's epigenetic regulation and its interaction with circadian rhythms reveal opportunities to optimize therapeutic strategies by aligning glucocorticoid administration with circadian timing. In this review, we provide an overview of the glucocorticoid receptor's role in cardiac physiology, detailing its genomic and non-genomic pathways, interactions with epigenetic and circadian regulatory mechanisms, and implications for cardiovascular disease. By dissecting these molecular interactions, this review outlines the potential of epigenetically informed and circadian-timed interventions that could change the current paradigms of CVD treatments in favor of precise and effective therapies.

Adequate energy intake is crucial for athletic performance and recovery. However, many endurance athletes experience Low Energy Availability (LEA), which, if prolonged, can detrimentally impact both health and performance.

A total of 55 endurance athletes (23 females; 45  ±  13 years, 1.64  ±  0.06 m, 64.4  ±  11.4 kg and 32 males; 44  ±  13 years, 1.76  ±  0.18 m, 78.8  ±  9.2 kg) underwent physical assessments and completed questionnaires on dietary habits, training loads, and psychological stress. Dual-Energy X-ray Absorptiometry (DEXA) scans measured bone mineral density (BMD) in the lumbar L1-L4 spine, and body composition. Risk of LEA burnout, and psychological strain were assessed using sport-specific questionnaires.

Seventy-seven percent of female athletes were identified as at risk of LEA by the LEAF-Q. These females had higher body weight and fat percentage than those at low risk of LEA. Male athletes had a higher prevalence of low lumbar BMD (31%) compared to females, associated with older age, and longer training histories. Although only 9% of female athletes had low-BMD, those affected had a history of amenorrhea and were identified as at risk of LEA by the LEAF-Q.

A high proportion of endurance athletes had low-BMD and were at risk of LEA. This underscores the need for targeted nutritional strategies to mitigate the risks associated with LEA and promote overall athlete well-being.

The hypothalamic-pituitary-adrenal axis regulates the secretion of glucocorticoids in response to environmental challenges. In the brain, a nuclear receptor transcription factor, the glucocorticoid receptor, is an important component of the hypothalamic-pituitary-adrenal axis's negative feedback loop and plays a key role in regulating cognitive equilibrium and neuroplasticity. The glucocorticoid receptor influences cognitive processes, including glutamate neurotransmission, calcium signaling, and the activation of brain-derived neurotrophic factor-mediated pathways, through a combination of genomic and non-genomic mechanisms. Protein interactions within the central nervous system can alter the expression and activity of the glucocorticoid receptor, thereby affecting the hypothalamic-pituitary-adrenal axis and stress-related cognitive functions. An appropriate level of glucocorticoid receptor expression can improve cognitive function, while excessive glucocorticoid receptors or long-term exposure to glucocorticoids may lead to cognitive impairment. Patients with cognitive impairment-associated diseases, such as Alzheimer's disease, aging, depression, Parkinson's disease, Huntington's disease, stroke, and addiction, often present with dysregulation of the hypothalamic-pituitary-adrenal axis and glucocorticoid receptor expression. This review provides a comprehensive overview of the functions of the glucocorticoid receptor in the hypothalamic-pituitary-adrenal axis and cognitive activities. It emphasizes that appropriate glucocorticoid receptor signaling facilitates learning and memory, while its dysregulation can lead to cognitive impairment. This provides clues about how glucocorticoid receptor signaling can be targeted to overcome cognitive disability-related disorders.

Maternal behavior is disturbed by exposure to environmental adversity, including resource scarcity, which can impair maternal care and increase adverse caregiving behaviors like abuse and maltreatment. In rats, exposure to resource scarcity disrupts mother-infant interactions and results in adverse pup-directed maternal behaviors. These changes in maternal behavior are thought to be due to hyperactivity within the hypothalamic-pituitary-adrenal (HPA)-axis, which mediates the stress response. In accordance, upregulation of HPA-axis function is sufficient to drive changes in maternal behavior in rodents. Based on these data, we hypothesized that scarcity-adversity induced changes in maternal behavior would be associated with HPA-axis hyperactivity, as indexed by elevated basal levels of the stress hormone corticosterone (CORT) in rat dams. To test this, we employed a scarcity-adversity paradigm based on creating an impoverished cage environment during postpartum days (PD) 2-9 and examined effects on naturalistic maternal behaviors and basal fecal boli CORT levels (PD 3, PD 5, PD 7) or basal and stress-induced serum CORT levels (PD 9). Surprisingly, rat dams exposed to scarcity-adversity exhibited increases in adverse pup-directed behaviors (e.g., stepping, dragging, shoving) but no elevations in basal or stress-induced CORT levels at any of the time-points assessed. These findings suggest that scarcity-adversity can increase adverse caregiving in a CORT-independent manner. Thus, increases in basal CORT levels are not necessary to induce aberrant maternal behavior in the scarcity-adversity paradigm.

Major depressive disorder (MDD) presents as a multifaceted syndrome with complex pathophysiology and variable treatment responses, posing significant challenges in clinical management. Neuroinflammation is known to play pivotal mechanism in depression, linking immune responses with central nervous system (CNS) dysfunction. This review explores the interplay between peripheral and central inflammatory processes in MDD, emphasizing discrepancies in biomarker validity and specificity. While peripheral markers like cytokines have historically been investigated as proxies for neuroinflammation, their reliability remains contentious due to inconsistent findings, lack of correlation with neuroinflammatory markers, the influence of confounding variables, and the role of regulatory mechanism within the CNS. Additionally, the human brain shows a pattern of regionalized inflammation. Current methodologies for investigating neuroinflammation in humans in vivo, including neural-derived extracellular vesicles (EVs) and positron emission tomography (PET) neuroimaging using translocator protein, offer promising avenues while facing substantial limitations. We propose that future research in MDD may benefit from combined microglia-derived EV-TSPO PET neuroimaging analyses to leverage the strengths and mitigate the limitations of both individual methods.

Patients with chronic kidney disease (CKD) exhibit a disproportionately elevated risk of stroke, frequently compounded by renal impairment. Therapeutic strategies for stroke based on Traditional Chinese Medicine's 'kidney-brain axis' theory demonstrate clinical efficacy, indicating that there may be a potential association between chronic kidney disease and stroke, which needs further exploration and verification.

In this study, databases such as GEO, NHANES, and GWAS were used to collect data related to CKD and stroke. GEO gene data enrichment analysis was used to explore possible mediating factors between CKD and stroke. NHANES clinical data were used to verify the GEO data analysis results. Mendelian randomization was used to confirm the causal relationship between CKD and stroke and verify the association effect of mediating factors in these two diseases.

Cross-gene analysis and transcription factor analysis of GEO data revealed that lipid-related pathways may have a mediating effect on the relationship between CKD and stroke. Logistic regression analysis based on NHANES data revealed that changes in LDL-C, HDL-C, TC, and TG can affect the occurrence of stroke. Mendelian randomization analysis was used to determine the causal relationship between CKD and stroke and verified the mediating effects of lipid factors, such as LDL-C, HDL-C, TC, and TG, indicating that LDL-C, HDL-C, TC, and TG may be potential mediating factors for these two diseases. Our findings highlight the clinical relevance of lipid pathways in bridging CKD and stroke. By integrating predictive biomarkers and multi-level diagnostics, this study paves the way for AI-driven precision medicine in stroke prevention. Specifically, machine learning approaches could enhance risk stratification of high-risk CKD cohorts, enabling tailored interventions such as lipid-lowering therapies and personalized monitoring protocols. These strategies align with emerging paradigms in healthcare benefits and population-specific management.

This study provides new insights into the interactive relationship between CKD and stroke and provides a scientific basis for the process of syndrome differentiation and the treatment of stroke under the guidance of the "kidney-brain correlation". Moreover, the influence of mediating factors related to lipid metabolism on the occurrence of these two diseases was investigated, which deepened researchers' understanding of the potential association mechanism between the two diseases.

Migraine is a complex neurological disorder frequently associated with hypothalamic dysfunction. This brain region is essential for maintaining homeostasis due to its regulation of autonomic, endocrine, and circadian systems. While the pathophysiology of migraine remains incompletely understood, clinical features such as the cyclic nature of attacks and symptoms, including nausea, vomiting, yawning, irritability, and sensitivity to light, indicate a significant role for the hypothalamus. Further, potential triggers of migraine, such as stress and disruption to feeding habits, also impact hypothalamic mechanisms. The higher prevalence of migraine in women compared to men suggests a link to hormonal fluctuations involving estrogen, progesterone, and prolactin. These hormones interact with the hypothalamus, potentially influencing the onset and severity of migraine episodes. Additionally, the hypothalamus synthesizes neuropeptides such as orexins, neuropeptide Y, PACAP, oxytocin, and vasopressin, which are all implicated in migraine mechanisms. Understanding the interplay between the hypothalamus, sex hormones, and neuropeptides offers valuable opportunities for endogenous targeted migraine therapies. In this review we discuss hypothalamic contributions to migraine pathophysiology, highlighting the mechanisms affected by hypothalamic connections, neuropeptides, and hormones, and their role as migraine triggers, particularly focusing on factors like stress, fasting, and changes in sleep patterns.

Exposure to social stress, such as neighborhood violence, affects the body's psychoneuroendocrinology, contributing to multiple chronic diseases. Hair cortisol concentration (HCC) is a novel proxy measure of chronic stress response. While Black Americans are exposed to social stress at a higher level, the association between violence exposure and HCC has not been extensively examined in older Black men. Intersectionality of race, gender, and class may disproportionately affect Black men to exposure to violence, thus, elevated HCC.

Black men aged 45 and older were recruited from four barbershops in predominantly Black communities in Chicago. Hair samples were collected by barbers for HCC, and a set of survey questions concerning perceived stress, exposure to violence, and fear of crime were collected along with demographic characteristics and residential community area. Using the residential community area, the homicide and poverty rates were appended. Descriptive statistics and a two-level hierarchical regression were used to examine the association between HCC and individual- and neighborhood-level factors.

A total of 127 participants were included in the final analytic sample. The mean HCC was 22.3 pg/mg for those living in the lowest quartile homicide rates, while the mean HCC was 40.2 pg/mg for participants residing in the highest quartile homicide areas. Log-HCC was significantly correlated with homicide rate (r = .264, P < .01) and perceived violence exposure (r = .195, p = .028) but not with perceived stress (r = .100, p = .508) or fear of crime (r = .124, p = .136). Multilevel regression models showed that log-HCC was significantly higher for those living in the highest homicide quartile compared to HCC in the lowest quartile homicide rate (p < .01), controlling for age, being a current smoker, being married, being unemployed, and perceived stress, violence exposure, and fear of crime measures.

HCC was significantly higher for Black men residing in neighborhoods with high violence. The study highlights how Black men, particularly those in segregated urban areas, experience disproportionate exposure to social stressors such as neighborhood violence. The study findings demonstrate that multiple social positions compound exposure to systemic inequities, which results in elevated risk of mental and physical health conditions.

Anthropogenic factors are those that occur due to human activities. The exposome is proposed to complement the genome, wherein an individual's exposure begins before birth. The range of exposures includes physical, chemical, dietary, lifestyle, biological, and occupational sources. Exposome has a positive or negative influence on neuroplasticity during different stages of life. A comprehensive study of the exposome is thus necessary to incorporate these factors and their influence on the individual, community, and the population as a whole. Exposomic research and global health present significant opportunities for interdisciplinary research. This review gives an overview of the exposome and its influence on neuroplasticity. It proposes methods to study the exposome on neuroplasticity across the lifespan of the individual. This is possible with the use of self-reported data, large-scale cohort formation, physiological sensors, neuroimaging, omics, molecular biology, and systems approaches. These approaches aim to provide a holistic understanding of an individual's neurological well-being and its implications for the population at large. This will also enable the designing of novel preventive and treatment strategies for managing neurological disorders.

Since ancient times, humanity has been exploring natural substances with the aim of increasing stress resistance, enhancing biochemical homeostasis, and treating different diseases. In this way, the objective of the present review is to compare the biological effects of cannabinoids (CNBs) with adaptogens, this exploration allows us to consider the controversy if they can be classified together considering the effects on the body. First, the work revises different features of adaptogens such as their chemical structure, ligand-receptors properties, and homeostasis-stress capabilities. Also, this review includes an overview of preclinical and clinical studies of the effect of adaptogens considering a broad spectrum of adverse biological, chemical, and physical factors. Then, the work does a review of the CNBs effects on the body including the principal uses for the treatment of several diseases as neurodegenerative disorders, arthritis, cancer, cardiovascular affections, diabetes, anxiety, chronic pain, among others. In addition, the different characteristics of the specific endocannabinoid system are described explaining the wide CNBs body effects. Finally, this review presents a comparative analysis between CNBs and adaptogens properties, expecting to contribute to understanding if CNBs can be classified as adaptogens.

Glucocorticoids (GCs) are widely used anti-inflammatory agents that inhibit growth in children. However, their mechanisms and effect on the growth hormone (GH)/insulin-like growth factor (IGF)-1 axis remain unclear.

This study, we aimed to establish a mouse model of GC-induced growth retardation during the critical growth period and explore the underlying mechanisms. Additionally, we aimed to identify novel biomarkers and potential therapeutic agents for GC-induced growth impairment.

Four-week-old mice were treated with GCs for two weeks and subsequently assessed for body length, weight, and body composition. Immunohistochemical analysis of the growth plate in the proximal tibia and biochemical assays of blood were performed to evaluate changes in growth plate length and GH/IGF-1 axis. KMT1A expression and its effects on Ghr expression were examined, and the impact of berberine on GC-induced growth retardation was assessed.

GCs significantly reduced growth by impairing growth plate expansion, disrupting the GH/IGF-1 axis, and downregulation of the GH receptor (Ghr) and Igf-1 levels in the liver. These changes were attributed to the upregulation of the H3K9 trimethyltransferase KMT1A, which decreased Ghr transcription in the liver. In vitro screening of natural compounds revealed that berberine chloride hydrate decreased the KMT1A levels and increased GHR levels. Berberine chloride hydrate also effectively ameliorated GC-induced growth retardation by restoring Ghr expression via KMT1A inhibition, thereby enhancing the circulating IGF-1 levels.

Overall, our findings highlight the potential of targeting KMT1A using berberine chloride hydrate as an epigenetic modifier to treat GC-induced growth impairment.

The hypothalamic-pituitary-thyroid axis has been well-known. However, whether follicular thyroid adenoma (FTA) could affect brain glucose metabolism is still unknown. Therefore, we explored the brain glucose metabolic characteristics of FTA with Fluorodeoxyglucose F18 positron emission tomography/magnetic resonance imaging.

Totally 30 FTA patients without clinical symptoms (FTA group), and 60 age- and sex-matched healthy controls (HC group) were included and randomly divided into cohort A and B in 2:1 ratio. Cohort A was analyzed with scaled sub-profile model/principal component analysis (SSM/PCA) for pattern identification. Cohort B was calculated the individual scores to validate expression of the pattern. Then we calculated the metabolic connectivity based on characteristics of the pattern to investigate the underlying mechanism. Finally, we constructed metabolic brain networks and analyzed the topological properties to further explore the brain metabolic model.

In SSM/PCA, FTA group showed an almost global, left-right symmetrical pattern. In metabolic connectivity, FTA group showed increased metabolic connectivity in brain regions of the sensorimotor network, ventral default mode network (DMN), posterior salient network, right executive control network (ECN), visuospatial network and language network when compared to HC group, and showed decreased connectivity in dorsal DMN and left ECN. In topological properties of brain network, FTA group showed an increased betweenness centrality (BC) in left rolandic operculum, a decreased BC in superior temporal gyrus, increased BC and Degree in right precentral gyrus, increased D in right parahippocampal gyrus and left hippocampus, and decreased D and efficiency in right orbital part of middle frontal gyrus (FDR correction for multiple comparisons, P < 0.05).

Although FTA patients are not yet symptomatic, their brain metabolic characteristics include extensive brain alterations, disrupted internal connectivity, not only involving brain regions associated with endocrine activity, but also brain networks and regions associated with motor, emotion and cognition.

Laboratory-based stress inductions are commonly used to elicit acute stress but vary widely in their procedures and effectiveness. We compared the effects of stress induction techniques on measures of two major biological stress systems: the early sympathetic-adrenal-medullary (SAM) and the delayed hypothalamic-pituitary-adrenal (HPA) axis response.

A review and meta-analysis to examine the relationship between stress induction techniques on cardiorespiratory and salivary measures of SAM and HPA system activity.

A systematic literature search identified 245 reports and 700 effects.

The overall effect of stress induction techniques on the stress response was moderate (Fisher's zr = 0.44), inducing stronger SAM-related (zr = 0.48) versus HPA-related (zr = 0.37) responses. Three factors moderated these associations: the stress system examined (SAM vs HPA), the specific stress induction technique employed (e.g., Cold Pressor), the physiological sampling time relative to the stress induction, and participant sex. Loud music elicited the most robust SAM-related effects, whereas combined stress inductions elicited the most robust HPA-related effects. Men showed stronger stress responses than women.

Stress induction techniques variably elicit SAM - and HPA-related responses. Results recommend specific induction techniques for targeting stress systems, highlighting the importance of carefully selecting methodologies in laboratory contexts.

The word "cancer" evokes myriad emotions, ranging from fear and despair to hope and determination. Cancer is aptly defined as a complex and multifaceted group of diseases that has unapologetically led to the loss of countless lives and affected innumerable families across the globe. The battle with cancer is not only a physical battle, but also an emotional, as well as a psychological skirmish for patients and for their loved ones. Cancer has been a part of our history, stories, and lives for centuries and has challenged the ingenuity of health and medical science, and the resilience of the human spirit. From the early days of surgery and radiation therapy to cutting-edge developments in chemotherapeutic agents, immunotherapy, and targeted treatments, the medical field continues to make significant headway in the fight against cancer. However, even after all these advancements, cancer is still among the leading cause of death globally. This urges us to understand the central hallmarks of neoplastic cells to identify novel molecular targets for the development of promising therapeutic approaches. Growing research suggests that stress mediators, including epinephrine, play a critical role in the development and progression of cancer by inducing neoplastic features through activating adrenergic receptors, particularly β-adrenoreceptors. Further, our experimental data has also shown that epinephrine mediates the growth of T-cell lymphoma by inducing proliferation, glycolysis, and apoptosis evasion via altering the expression levels of key regulators of these vital cellular processes. The beauty of receptor-based therapy lies in its precision and higher therapeutic value. Interestingly, the enhanced expression of β-adrenergic receptors (ADRBs), namely ADRB2 (β2-adrenoreceptor) and ADRB3 (β3-adrenoreceptor) has been noted in many cancers, such as breast, colon, gastric, pancreatic, and prostate and has been reported to play a pivotal role in facilitating cancer growth mainly by promoting proliferation, evasion of apoptosis, angiogenesis, invasion and metastasis, and chemoresistance. The present review article is an attempt to summarize the available findings which indicate a distinct relationship between stress hormones and cancer, with a special emphasis on epinephrine, considered as a key stress regulatory molecule. This article also discusses the possibility of using beta-blockers for cancer therapy.

Irritable bowel syndrome is a gastrointestinal disorder due to multiple pathologies. While patients with this condition experience anxiety and depressed mood more frequently than healthy individuals, it is unclear how gastrointestinal dysfunction interacts with such neuropsychiatric symptoms. Data suggest that irritable bowel syndrome patients predominantly display a lower zinc intake, which presumably impairs enterochromaffin cells producing 5-hydroxytryptamine, gut bacteria fermenting short-chain fatty acids, and barrier system in the intestine, with the accompanying constipation, diarrhea, low-grade mucosal inflammation, and visceral pain. Dyshomeostasis of copper and zinc concentrations as well as elevated pro-inflammatory cytokine levels in the blood can disrupt blood-cerebrospinal fluid barrier function, leading to locus coeruleus neuroinflammation and hyperactivation with resultant amygdalar overactivation and dorsolateral prefrontal cortex hypoactivation as found in neuropsychiatric disorders. The dysregulation between the dorsolateral prefrontal cortex and amygdala is likely responsible for visceral pain-related anxiety, depressed mood caused by anticipatory anxiety, and visceral pain catastrophizing due to catastrophic thinking or cognitive distortion. Collectively, these events can result in a spiral of gastrointestinal symptoms and neuropsychiatric signs, prompting the progression of irritable bowel syndrome. Given that the negative feedback mechanism in regulation of the hypothalamic-pituitary-adrenal axis is preserved in a subset of neuropsychiatric cases, dorsolateral prefrontal cortex abnormality accompanied by neuropsychiatric symptoms may be a more significant contributing factor in brain-gut axis malfunction than activation of the hypothalamic corticotropin-releasing hormone system. The proposed mechanistic model could predict novel therapeutic interventions for comorbid irritable bowel syndrome and neuropsychiatric disorders.

In functional dyspepsia, increased gut permeability, low-grade inflammation, and altered sensorimotor function have been reported. Both stress and corticotropin-release hormone (CRH) have been shown to increase small bowel permeability in a mast-cell-dependent manner. Moreover, eosinophil-derived CRH has been implicated in mast cell activation. The aim of this study was to evaluate whether CRH administration alters duodenal permeability and immune activation in healthy volunteers (HVs). An intravenous bolus of 100-µg CRH or placebo was administered in HVs in a crossover, double-blind, randomized manner. Two hours later, a gastroscopy was performed to measure permeability in Ussing chambers and to count mast cells and eosinophils on duodenal biopsies. Supernatant was assessed for eosinophil-derived neurotoxin (EDN), tryptase, and chymase. In addition, CRH was administrated ex vivo to baseline biopsies pretreated with or without lodoxamide. Results are described as means ± SD. P values < 0.05 were considered significant. Twenty HVs completed the study. Mast cell or eosinophil counts were not significantly altered after CRH versus Placebo (respectively P = 0.31 and P = 0.069). Tryptase, but not chymase, significantly decreased after CRH (respectively P = 0.037 and P = 0.44) with a trend for a decrease in EDN (P = 0.053). Permeability was unaltered comparing both conditions. Ex vivo, transepithelial electrical resistance significantly decreased after CRH exposure compared with baseline (P = 0.010), which was not prevented by pretreatment with lodoxamide. In vivo CRH administration reduced tryptase levels in the supernatant of duodenal biopsies without affecting permeability, whereas ex vivo duodenal permeability increased regardless of mast cell stabilization. These results suggest the involvement of mast cells in regulating gut permeability in HVs in response to CRH, possibly influenced by in vivo compensatory mechanisms.NEW & NOTEWORTHY Our investigation breaks new ground by directly examining the effects of corticotropin-release hormone (CRH) on duodenal alterations, including permeability and immune activation, in healthy subjects. Intriguingly, our findings highlight disparities between ex vivo and in vivo pathways affecting duodenal permeability, offering novel insights into the potential pathophysiology of CRH on the duodenum.

Stress activates the hypothalamic-pituitary-adrenal (HPA) axis of which cortisol is an end product. 'Allostatic load' is where systems including the HPA axis are exposed to high, cumulative, physiologic burdens (such as chronic breathlessness) leading to flatter diurnal cortisol slopes and poorer health outcomes. The aim of this hypothesis-generating study explored longitudinal changes in cortisol secretion and any associated changes in breathlessness after introducing regular, low dose morphine or placebo.

This was an optional, hypothesis-generating sub-study embedded in a multi-site, randomised, double-blind, placebo-controlled trial (RCT) of regular, low-dose morphine for chronic breathlessness and chronic obstructive pulmonary disease. In a blinded dose-increment algorithm by week three, doses were 0 mg-32 mg. Participants in the RCT could elect to continue in a six-month blinded extension. This sub-study excluded people who used non-inhaled corticosteroids in the previous month or were on subcutaneous insulin. Participants collected saliva for cortisol assays for two days at baseline, and ends of weeks 1, 3 and 12 at 3,6 and 12 h after waking, generating sufficient data to calculate diurnal cortisol slopes and areas under the curve (AUC). Samples were analysed using ELISA. Correlations between diurnal cortisol profiles (slope and AUC) and a range of measures were explored.

Twenty mostly female former smokers were in this sub-study. At baseline and the end of week 1, one-way ANOVA between-group analyses showed no significant differences in the log-transformed cortisol slope or ln-AUC. There was a strong correlation between the age-adjusted Charlson Comorbidity Index (CCI) and ln-AUC (r=-0.70, p < 0.001) and moderate correlation with age (r=-0.43, p = 0.06). In the blinded extension study, there was a self-selecting blinded group (n = 7) all on active medication. Global impression of change (GIC) was highly correlated with the diurnal cortisol slope (rs = 0.98, p = 0.01), and with decrease in average breathlessness (r = 0.89, p = 0.04).

This hypothesis-generating study did not show a relationship between the diurnal cortisol profile and morphine in people with chronic breathlessness and COPD. For the sub-group still on study at 12weeks, the cortisol curves became steeper as average breathlessness decreased and as global impression of change (GIC) improved, suggesting that reducing breathlessness may potentially positively impact the HPA axis in a sub-group of people.

Registration Number NCT02720822 date registered 28/03/2016.

Adverse childhood experiences (ACEs) are linked to later anxiety and depression, and inflammation has been implicated as a mediating mechanism. Black and Latinx men who have sex with men (MSM) face higher prevalences of ACEs, anxiety, and depression compared to White, heterosexual peers. Understanding the links between ACEs and mental health is crucial to addressing these disparities.

This study used structural equation modeling to test moderated mediation models examining inflammation as a mediator of the relationship between ACEs and symptoms of anxiety/depression and minority stress as a moderator on the path between ACEs and inflammation. Data was from a community sample of Black and Latinx MSM (n = 246; mean age = 22.6).

ACEs were significantly associated with symptoms of anxiety (B = 0.414; p < 0.001) and depression (B = 0.346; p < 0.001), but inflammation did not show a significant mediating effect. Additionally, the interaction between ACEs and minority stress had no significant indirect effect on anxiety/depression.

These findings underscore the possibility that inflammation may not represent the global perturbations of stress processes after ACEs at younger ages, particularly among a relatively healthy sample of emerging adults.

Sleep, a state of reduced responsiveness and distinct brain activity, is crucial across the animal kingdom. This review explores the potential adaptive functions of REM sleep in adapting to stress, emphasizing its role in memory consolidation, emotional regulation, and threat processing. We further explore the underlying neural mechanisms linking stress responses to REM sleep. By synthesizing current findings, we propose that REM sleep allows animals to "rehearse" or simulate responses to danger in a secure, offline state, while also maintaining emotional balance. Environmental factors, such as predation risk and social dynamics, further influence REM sleep. This modulation may enhance survival by optimizing stress responses while fulfilling physiological needs in animals. Insights into REM sleep's role in animals may shed light on human sleep in the context of modern stressors and sleep disruptions. This review also explores the complex interplay between stress, immunity, sleep disruptions-particularly involving REM sleep-and their evolutionary underpinnings.

Bioactive peptides consist of multiple linked amino acids that are secreted from cells and act on specific receptors in order to transmit information from one cell to another. Through signal transduction, bioactive peptides regulate various physiological functions in the body, and the discovery of new bioactive peptides is therefore likely to lead to the development of various diagnostic and therapeutic agents. In this article, we have focused on the bioactive peptides that are known as feeding regulatory peptides. They are among the bioactive peptides discovered as ligands for G protein-coupled receptors (GPCRs), and we have reviewed their diverse functions. In addition, the status of structural analysis of GPCRs, which is necessary in the drug discovery process, and research on orphan GPCRs, for which new ligands are expected to be discovered in the future, is introduced to systematize modern peptide research and discuss future developments in bioactive peptide research.

The current discovery that the gut microbiome, which contains roughly 100 trillion microbes, affects health and disease has catalyzed a boom in multidisciplinary research efforts focused on understanding this relationship. Also, it is commonly demonstrated that the gut and the CNS are closely related in a bidirectional pathway. A balanced gut microbiome is essential for regular brain activities and emotional responses. On the other hand, the CNS regulates the majority of GI physiology. Any disruption in this bidirectional pathway led to a progression of health problems in both directions, neurological and gastrointestinal diseases. In this review, we hope to shed light on the complicated connections of the microbiome-gut-brain axis and the critical roles of gut microbiome in the early development of the brain in order to get a deeper knowledge of microbiome-mediated pathological conditions and management options through rebalancing of gut microbiome.

Variation in parenting behavior is widespread across the animal kingdom, both within and between species. There are two ecotypes of the three-spined stickleback fish (Gasterosteus aculeatus) that exhibit dramatic differences in their paternal behavior. Males of the common ecotype are highly attentive fathers, tending to young from eggs to fry, while males of the white ecotype desert offspring as eggs. As the pituitary is a key regulator in the hypothalamic-pituitary-adrenal (HPA) axis and the hypothalamic-pituitary-gonadal (HPG) axis between the brain and body, its peptides may influence parenting behaviors. Here, we utilized matrix-assisted laser desorption ionization mass spectrometry (MALDI-MS) for high-throughput peptide analysis in single cells of pituitaries from both three-spined stickleback ecotypes. Peptide mass fingerprinting was performed using an in silico generated peptide library to identify detected prohormones. Differential analysis revealed POMC-derived peptides, MCH-derived peptides, and oxytocin as significantly different between the two ecotypes, with higher oxytocin levels in the common ecotype. Interestingly, these subtle chemical differences were not captured by Leiden clustering of the cellular phenotypes. These results call for further investigation of the neurochemical basis for parenting in sticklebacks.

Touch has been shown to regulate emotions, stress responses, and physical pain. However, its impact on cognitive functions, such as inhibitory control, remains relatively understudied. In this experiment, we explored the effects of low-force, slow-moving touch-designed to optimally activate unmyelinated cutaneous low-threshold mechanoreceptor C-tactile (CT) afferents in human hairy skin-on inhibitory control and its psychophysiological correlates using the Stroop Task, a classic paradigm commonly employed to assess inhibitory control capacity. The Stroop Task was repeated twice before and once after receiving either gentle touch or no-touch. Participants were assigned to two groups: the touch group (n = 36), which received low-force, slow-moving touch on their forearms at a stroking velocity of ~3 cm/s, and the no-touch group (n = 36), which did not receive any touch stimulation. Changes in autonomic nervous system activity were also assessed by measuring heart rate variability (HRV) and skin conductance levels before and during cognitive performance. Compared to the no-touch group, participants who received gentle, low-force, slow-moving touch demonstrated faster responses and higher HRV during the Stroop Task. Additionally, within the touch group, individuals with higher HRV exhibited even quicker performance on the cognitive task. While we cannot draw definitive conclusions regarding the CT velocity-specific effect, these results provide preliminary evidence that low-force, slow-moving touch may influence cognitive processes involved in the inhibitory control of goal-irrelevant stimuli.

The constrained disorder principle (CDP) defines complex biological systems based on inherent variability. Allostasis refers to the physiological processes that help maintain stability in response to changing environmental demands. Allostatic load describes the cumulative wear and tear on the body resulting from prolonged exposure to stress, and it has been suggested to mediate the relationship between stress and disease. This study presents the concepts of CDP and allostasis while discussing their similarities and differences. We reviewed the current literature on the potential benefits of introducing controlled doses of biological noise into interventions, which may enhance the effectiveness of therapies. The paper highlights the promising role of variability provided by a CDP-based second-generation artificial intelligence system in improving health outcomes.

Sexual dimorphism in immune responses is well documented, but the underlying mechanisms remain incompletely understood. Here, we identified a subset of corticotropin-releasing hormone (CRH) neurons that express androgen receptors (ARs) as key mediators of sex differences in restraint-induced immunosuppression. Mechanistically, androgens directly activate AR-positive CRH neurons, enhancing the hypothalamic-pituitary-adrenal axis activation. This results in elevated corticosterone levels in response to restraint stress, leading to increased immune cell apoptosis and immune organ atrophy in male mice. Conditional knockout of ARs in CRH neurons eliminated this sexual dimorphism, highlighting ARs in CRH neurons as pivotal regulators of sex-specific immune responses to stress.

Different conditions of production systems including stocking density, thermal conditions, and behavior restriction can have a significant detrimental effect on the health and performance of laying hens. The conventional cage system is one of the systems that have been reported to cause stress problems in birds, due to social and behavioral stress. Emerging technologies have facilitated a deeper understanding of animal responses to various scenarios and can be an additional tool to conventional ones to assess animal welfare, where transcriptomic analysis has the potential to show the genetic changes that occur in response to stress. According to this, the aim of this work was to characterize the liver transcriptome of hens housed under two egg production systems (conventional cage and cage-free). Liver tissue from Hy-Line Brown hens housed in conventional cage (n = 3) and cage-free (n = 3) production systems at week 80 of age was processed using the Illumina platform to identify differentially expressed genes with a padj < 0.05. Regarding the differentially expressed genes, 138 genes were found, of which 81 were upregulated and 57 downregulated. Some of the genes of interest were TENM2, GRIN2C, and ACACB, which would indicate greater fat synthesis in the liver of caged hens. The enriched KEGG pathways were DNA replication and the cell cycle. In conclusion, it was identified that the cage production system may influence DNA replication and the cell cycle since the genes related to these terms were found suppressed, which would indicate cellular instability.

Subanesthetic doses of (R,S)-ketamine (ketamine) have demonstrated rapid and robust antidepressant effects in individuals with depression. However, individual variability in response to ketamine exists, and current biomarkers of ketamine treatment response are not entirely understood. Preclinical evidence suggests a link between hypothalamic-pituitary-adrenal (HPA) axis activation, a determinant of the stress response system, and ketamine's efficacy in stressed mice exhibiting enhanced antidepressant responses. Here, we assessed the relationship between HPA axis, major depression features, and antidepressant response to ketamine in humans.

We investigated 42 participants following medication washout with treatment-resistant depression who participated in a randomized, placebo-controlled, crossover trial receiving intravenous ketamine. Plasma levels of corticotropin-releasing factor (CRF), adrenocorticotropic hormone (ACTH), and cortisol were measured at baseline. Ketamine's antidepressant effects were assessed using the Montgomery-Asberg Depression Rating Scale.

We found that baseline HPA axis hormone levels did not significantly moderate the antidepressant effects of ketamine. However, a negative association was observed between ACTH and CRF levels and the overall duration of depressive episodes, suggesting potential biomarker implications. Also, a negative correlation between baseline depressive scores and age of onset was observed, suggesting that the severity of depression might be greater if it develops at a younger age, indicating more enduring stress on the brain and body.

Although we did not find a moderation effect of the plasma HPA axis hormones on the antidepressant effects of ketamine, moderation effects of the brain HPA axis hormones cannot be precluded and warrants further investigation. Importantly, our results implicate HPA axis components as potential biomarkers for the duration of depressive episodes.

The COVID-19 (C-19) pandemic has highlighted the significance of understanding the long-term effects of this disease on the quality of life of those infected. Long COVID-19 (L-C19) presents as persistent symptoms that continue beyond the main illness period, usually lasting weeks to years. One of the lesser-known but significant aspects of L-C19 is its impact on neuropsychiatric manifestations, which can have a profound effect on an individual's quality of life. Research shows that L-C19 creates neuropsychiatric issues such as mental fog, emotional problems, and brain disease symptoms, along with sleep changes, extreme fatigue, severe head pain, tremors with seizures, and pain in nerves. People with cognitive problems plus fatigue and mood disorders experience great difficulty handling everyday activities, personal hygiene, and social interactions. Neuropsychiatric symptoms make people withdraw from social activity and hurt relationships, thus causing feelings of loneliness. The unpredictable state of L-C19 generates heavy psychological pressure through emotional suffering, including depression and anxiety. Neuropsychiatric changes such as cognitive impairment, fatigue, and mood swings make it hard for people to work or study effectively, which decreases their output at school or work and lowers their job contentment. The purpose of this narrative review is to summarize the clinical data present in the literature regarding the neuropsychiatric manifestations of L-C19, to identify current methods of diagnosis and treatment that lead to correct management of the condition, and to highlight the impact of these manifestations on patients' quality of life.

We assessed levels of mRNA encoding two glucocorticoid receptor (GR) isoforms (GRα and GRβ) in saliva and examined their relationship with hair cortisol levels and dental caries experience.

Adolescents and young adults were assessed for dental caries experience, and hair cortisol was measured by ELISA. RNA was extracted from whole saliva using TRIzol, followed by quantitative real-time PCR analysis of GRα, GRβ, and glyceraldehyde 3-phosphate dehydrogenase (GAPDH).

GRβ mRNA was not detectable in most samples, whereas GRα mRNA was observed in all samples. There were significantly lower levels of GRα mRNA in individuals with elevated hair cortisol levels than in those with normal cortisol levels. Levels of GRα mRNA did not differ significantly in individuals with dental caries experience compared to individuals with no caries experience.

We identified and quantified mRNA encoding GRα in saliva. Its levels were inversely associated with hair cortisol (a marker of chronic stress). Although caries experience was associated with hair cortisol levels, there was no significant association between GRα levels and caries experience. Chronic stress has been proposed to be associated with reduced expression of GRα and this association appears to hold for GRα mRNA levels in saliva.

There is growing evidence that organophosphate esters (OPEs) can act as endocrine-disrupting chemicals. However, only a few studies have assessed the effects of OPE exposure on one of the most important endocrine glands in the body, the adrenal gland. Our aim was to test the effects of a mixture of OPEs detected in Canadian house dust on adrenal function in Sprague Dawley rats. Adult male and female rats (n = 15 per treatment group) were administered either a vehicle or an OPE mixture (0.048, 1.6, or 48 mg/kg bw/d) for 70 to 72 d via their diet. With OPE exposure, adrenal glands from male adult rats were reduced in weight, whereas those of female rats showed an increase in weight. This led us to investigate whether OPEs induce sex-specific effects on adrenal gland function and the mechanisms involved. Serum levels of two adrenal hormones, aldosterone and corticosterone, were decreased only in male serum samples. Serum levels of renin and adrenocorticotropic hormone, which regulate aldosterone and corticosterone synthesis, respectively, were assessed. Exposure to the OPE mixture decreased renin levels only in males. Serum biochemistry analysis revealed that triglycerides and LDL cholesterol levels were increased in males. Transcriptomic analysis revealed that the top affected pathways in male adrenal glands from all three treatment groups were related to potassium channels, which play a role in regulating aldosterone and corticosterone levels. The most affected pathways in female adrenal glands were related to cholesterol biosynthesis and immune functions. These results show that an environmentally relevant mixture of OPEs affects adrenal function and that these effects are sex specific.

Introduction: This study examined the relationship between stress and pre-gaming (i.e., drinking prior to going out to an event) in female college students. Methods: Thirty-four female college students were grouped as pre-gamers or non-pre-gamers based on self-reported drinking patterns. They completed surveys about alcohol use and mental health and provided a set of salivary cortisol samples upon waking, 30 min later, and at 10am on the same day. Results: Pre-gamers and non-pre-gamers did not differ on demographics or psychosocial variables. Pre-gamers reported riskier drinking overall and had greater endorsement of social, coping, and enhancement drinking motives. Pre-gamers also had lower cortisol levels 30 min after waking and exhibited attenuated CAR. Conclusions: Female collegiate pre-gamers may differ from their peers not only in terms of alcohol consumption and drinking motives, but also on attenuated CAR, a physiological biomarker associated with stress dysregulation and vulnerability to addictive behaviors.

Integrative models of mental illness and health in psycho-oncology are aimed at all types of cancer, although the patients' experiences and issues may vary. This review summarizes the different theories and models of mental illness and health pertaining to the breast cancer experience and proposes an integrative phasic model applicable to the breast cancer trajectory. Five databases were searched for studies related to breast cancer mental health and illness theories and models. The PRISMA checklist form was used to extract the essential information from the included studies. Eleven theories and models on the experience of breast cancer were found. The integrative model based on these theories and models illustrates that the breast cancer experience is conceptualized as a trajectory with seven landmark 'events', each associated with a pathogenic 'challenge' leading to six possible 'symptoms', 1) psychological distress with anxious features, 2) psychological distress with depressive features, 3) non-specific distress 4) psychological distress with trauma-related features 5) low health-related quality of life, and 6) fear of recurrence. The Breast Cancer Psychological Integrative Phasic Model is supported by a simple clinical tool (BreastCancerPsych - Integrative Clinical Tool) that serves as a valuable resource throughout the care trajectory. These integrative phasic model and clinical tool are designed to help mental health clinicians formulate treatments that are tailored to the needs of their patients, especially for trajectories that are not marked by resilience.

Autoimmune disorders, including type 1 diabetes mellitus (T1DM) and systemic lupus erythematosus (SLE), are influenced by a combination of genetic, environmental, and immunological factors. Among these, stress, both physical and psychological, has been increasingly recognized as a significant contributor to disease onset and progression. This review explores the current literature on the relationship between stress and autoimmune diseases, focusing on the neuroendocrine pathways, such as the hypothalamic-pituitary-adrenal (HPA) axis, and the effects of glucocorticoids on immune modulation. These mechanisms contribute to clinical manifestations, such as disease flares or progression, highlighting the impact of stress on patient outcomes. Evidence suggests that psychological stress can precipitate the onset of T1DM in genetically predisposed individuals, with immune disruptions occurring before diagnosis. In SLE, both acute and chronic stress, particularly trauma-induced stress, has been linked to increased disease activity and flare-ups, largely due to stress-induced immune dysregulation that disrupts the balance between pro-inflammatory and anti-inflammatory cytokines. Despite the substantial evidence supporting the role of stress in autoimmune disease exacerbation, further research is necessary to fully understand the mechanisms by which stress influences autoimmune diseases and to develop effective stress management.

NaiKan Therapy, a method of self-reflection and introspection, has garnered considerable interest for its psychological benefits. However, its physiological impacts, particularly on hormonal regulation, remain underexplored. In this study, we aimed to investigate the effects of NaiKan Therapy on salivary oxytocin and cortisol release, shedding light on the psychophysiological mechanisms underlying this introspective practice. Sixty participants underwent Naikan Therapy sessions over five consecutive days, during which salivary samples were collected at multiple time points. Salivary oxytocin and cortisol levels were measured using enzyme-linked immunosorbent assay (ELISA) kits. Our results revealed significant increases in salivary oxytocin levels following NaiKan Therapy, suggesting a potential role of this practice in enhancing social bonding and emotional regulation. Conversely, salivary cortisol levels exhibited a decrease post-therapy, indicating a reduction in stress reactivity. These findings provide novel insights into the neuroendocrine mechanisms underlying NaiKan Therapy and highlight its potential as a holistic approach to improving mental wellbeing. Further research exploring the long-term effects of NaiKan Therapy and its implications for clinical practice is warranted.

Epilepsy stands out as one of the most prevalent chronic neurological conditions affecting companion animals. Recent research has increasingly focused on exploring the role of gut microbiota in influencing neurological conditions, like epilepsy. This influence stems from the bidirectional communication pathways between gut bacteria and the brain, which involve metabolic, neural, immunological, and endocrine mechanisms. In fact, a balanced and stable gut microbiota is essential to maintaining normal gut physiology and ensuring appropriate signaling along the gut-brain axis. Conversely, dysbiosis can have detrimental effects on gut physiology and may contribute to the development or exacerbation of neurological conditions, including epilepsy. Considering these findings, this review article aims to deepen the understanding of the mechanisms underlying the microbiota-gut-brain connection in the context of canine idiopathic epilepsy. Moreover, this review presents recent data on innovative gut-related therapeutic strategies for canine idiopathic epilepsy treatment.

Exposure to stressful life events is associated with a high risk of developing psychiatric disorders with a wide variety of symptoms. Cognitive symptoms in stress-related psychiatric disorders can be particularly challenging to understand, both for those experiencing them and for health care providers. To gain insights, it is important to capture stress-induced structural, epigenomic, transcriptomic, and proteomic changes in relevant brain regions such as the amygdala, hippocampus, locus coeruleus, and prefrontal cortex that result in long-lasting alterations in brain function. In this review, we will emphasize a subset of stress molecular mechanisms that alter neuroplasticity, neurogenesis, and balance between excitatory and inhibitory neurons. Then, we discuss how to identify genetic risk factors that may accelerate stress-driven or stress-induced cognitive impairment. Despite the development of new technologies such as single-cell resolution sequencing, our understanding of the molecular effects of stress in the brain remains to be deepened. A better understanding of the diversity of stress effects in different brain regions and cell types is a prerequisite to open new avenues for mechanism-informed prevention and treatment of stress-related cognitive symptoms.

Diabetes and depression have a bidirectional relationship, with negative impacts on glycemia, self-care, long-term complications, quality of life, and mortality. This review highlights key aspects of the interconnected and complex relationship between diabetes and depression, including how it affects health outcomes, depression duration and recurrence, age-specific manifestations, and recommendations for screening and nonpharmacological treatment.

Ongoing amphibian population declines are caused by factors such as climate change, habitat destruction, pollution and infectious diseases not limited to chytridiomycosis. Unfortunately, action is taken against these factors once population collapses are underway. To avoid these post hoc responses, wildlife endocrinology aims to analyse physiological mediators that predict future population declines to inform wildlife management. Mediators typically investigated are stress hormones known as glucocorticoids, which are produced by the Hypothalamus-Pituitary-Interrenal axis (HPI axis). The HPI axis is the part of the endocrine system that helps amphibians cope with stress. Chronic increases in glucocorticoids due to stress can lead to immune dysfunction, which makes amphibians more susceptible to infectious diseases. Despite this predictive potential of glucocorticoids, interpretation of glucocorticoid data is confounded by sampling design and type. Glucocorticoid monitoring classically involves blood sampling, which is not widely applicable in amphibians as some are too small or delicate to sample, and repeated samples are often valued. To address this, we tried to validate skin swabbing via corticosterone (CORT) and adrenocorticotropin hormone (ACTH) injections in adults of two amphibian species: Eastern red-spotted newts, Notophthalmus viridescens viridescens, with natural skin infections with Batrachochytrium dendrobatidis (Bd) upon collection in the field, and Northern leopard frogs, Rana (Lithobates) pipiens, raised in captivity and naïve to Bd exposure. Further, we determined the predictive potential of skin glucocorticoids on Bd load in the field via correlations in Eastern red-spotted newts. We found that hormones present in the skin are not related to the HPI axis and poorly predict infection load; however, skin hormone levels strongly predicted survival in captivity. Although skin swabbing is not a valid method to monitor HPI axis function in these species, the hormones present in the skin still play important roles in organismal physiology under stressful conditions relevant to wildlife managers.

This review explores the intricate relationships among the gut microbiota, dietary patterns, and mental health, focusing specifically on depression. It synthesizes insights from microbiological, nutritional, and neuroscientific perspectives to understand how the gut-brain axis influences mood and cognitive function.

Recent studies underscore the central role of gut microbiota in modulating neurological and psychological health via the gut-brain axis. Key findings highlight the importance of dietary components, including probiotics, prebiotics, and psychobiotics, in restoring microbial balance and enhancing mood regulation. Different dietary patterns exhibit a profound impact on gut microbiota composition, suggesting their potential as complementary strategies for mental health support. Furthermore, mechanisms like tryptophan metabolism, the HPA axis, and microbial metabolites such as SCFAs are implicated in linking diet and microbiota to depression. Clinical trials show promising effects of probiotics in alleviating depressive symptoms. This review illuminates the potential of diet-based interventions targeting the gut microbiota to mitigate depression and improve mental health. While the interplay between microbial diversity, diet, and brain function offers promising therapeutic avenues, further clinical research is needed to validate these findings and establish robust, individualized treatment strategies.

The relationship between stress, hair cortisol and alcohol consumption has mostly been investigated among clinical and adult study samples, with inconsistent findings. The present study aimed to examine cross-sectional and longitudinal associations between chronic stress, hair cortisol and average past-year alcohol consumption within a population-based sample of adolescents and young adults. At baseline of the epidemiological cohort study, N = 1180 individuals aged 14-21 from Dresden, Germany, were assessed (11/2015-12/2016). A maximum N = 1055 were analysed in cross-sectional analyses and a maximum N = 722 in longitudinal analyses (1-year follow-up). Multivariate linear regression analyses were conducted to reveal cross-sectional associations between perceived chronic stress, hair cortisol concentration and average past-year alcohol consumption in males and females. Longitudinally, weighted linear regression models examined relationships between (a) perceived chronic stress at baseline and altered hair cortisol concentration over 1 year, (b) perceived chronic stress/hair cortisol concentration at baseline and altered average alcohol consumption over 1 year and (c) average past-year alcohol consumption at baseline and altered stress/hair cortisol concentration over 1 year. Cross-sectionally, no significant relationships were found between stress, hair cortisol and average past-year alcohol consumption at baseline. In females, higher baseline perceived chronic stress was associated with an increase in hair cortisol concentration over 1 year, whereas no relationship was found in the cross-sectional analysis between baseline perceived chronic stress and baseline past-year average alcohol consumption. When using hair cortisol as a biomarker for stress perception, the focus of future research should be on potential time lags between perceived chronic stress and hair cortisol increase.

Maternal capabilities to engage in sensitive caregiving are important for infant development and mother-infant-interaction, however, can be negatively affected by cortisol due to a stress response. Previous research suggested that cortisol possibly impairs cognitive functions important for caregiving behavior, which potentially leads to less maternal sensitivity. However, studies investigating the influence of cortisol using endocrine parameters on the mother-infant-interaction during the early postpartum are lacking. In the current study, fifty-nine mother-infant-dyads participated in a laboratory face-to-face still-face (FFSF) observation when infants were 4 months of age. Maternal and infant positive, negative and matched behavior during the FFSF was microanalytically coded. Cortisol concentrations were obtained using hair and saliva samples. For salivary cortisol, the area under the curve with respect to ground (AUCG) was calculated using two saliva samples obtained after arrival and after the FFSF. Multiple block-wise hierarchical linear regression models were conducted to incorporate potential confounding factors (maternal age, parity, infant gestational age, infant sex) in a first step and, then, test for the association of hair and salivary cortisol with maternal and infant positive, negative and dyadic behavior in a second step. For both it was hypothesized that cortisol assessed in hair and saliva is negatively associated with positive and matched mother-infant-interaction, and positively associated with negative mother-infant-interaction. It could be shown that salivary but not hair cortisol as well as infant gestational age and infant sex related significantly to infant positive and negative affect as well as matched behavior during the reunion phase of the FFSF. Maternal positive affect was unrelated to any of the variables. The results are discussed in regard to the importance of maternal cortisol levels over a longer period of time and more acute situational levels for the mother-infant-interaction as well as the relevance of included confounding factors.

Acute psychosocial stress activates the hypothalamic-pituitary-adrenal (HPA) axis and triggers the release of cortisol, a commonly used biomarker of stress reactivity. Yet only 25 % of studies have reported a correlation between cortisol and affective responses to stress. This study aimed to examine whether cortisol reactivity following an acute psychosocial stressor in the laboratory correlated with concurrent positive and negative affect in adolescents, and whether early life adversity (ELA) moderated this relationship.

The current study examined the salivary cortisol response of 89 adolescents (46.1 % female) following administration of the Trier Social Stress Test for Children (TSST-C). Using 7 simultaneous measurements, changes in cortisol were compared to changes in concurrent affect using the Positive and Negative Affect Schedule (PANAS). Parents reported their child's exposure to ELA.

Within-person variability in cortisol was associated with higher negative affect at baseline, b = 1.43 (SE =.41), p < .001, as well as more rapid negative affective recovery following stress, b = -0.003 (SE =.002), p = .04. ELA-exposed participants were not more sensitive to this effect. Within-person variability in cortisol was not associated with positive affect at baseline or following the TSST-C on average, all ps > .27. However, within-person increases in cortisol were associated with decrements in positive affect among ELA-exposed individuals, all ps < .01, suggesting differential sensitivity to anhedonic effects of glucocorticoids.

Stress impacts affective states, in part through acute increases in HPA axis activity. The present data show that negative affect is more vulnerable to this than positive affect among adolescents. Further, adolescents with high ELA may be more vulnerable to decrements in positive affect in the acute aftermath of HPA axis activation. Whether this is a modifiable source of vulnerability to stress-related disease in this high-risk population remains to be understood.