Stress

Identifying children at risk for respiratory disorders involves understanding early risk factors. This study prospectively examines how specific types of early adversity influence childhood wheeze and how these vary by race and ethnicity. Analyses included N = 746 mother-infant dyads from an urban pregnancy cohort. Mothers completed the Lifetime Stressor Checklist-Revised (LSC-R), Edinburgh Postnatal Depression Scale (EPDS), Spielberger State-Trait Anxiety Inventory (STAI), Posttraumatic stress disorder Checklist–Civilian version (PCL-C), and Traumatic Events Screening Inventory (TESI) when infants were 6 months old to assess adverse childhood experiences (ACEs). Mothers reported child wheeze at 4-month intervals to index wheezing episodes from age 6–30 months. We first assessed independent associations between ACE measures and wheeze frequency using Poisson regression. We then used weighted quantile sum (WQS) regression to derive an ACEs mixture index to estimate joint associations with wheeze frequency in the overall sample and stratified by maternal race and ethnicity adjusting for child sex, maternal asthma and education. There was a 2.05 increase (95% CI = 1.21, 3.49) in wheeze frequency with each quintile increase of the ACEs index in Black/Black Hispanics; the TESI (72%) contributed most strongly to the mixture. In non-Black Hispanics, there was a 1.33 (95% CI = 1.05, 1.67) increase in wheeze frequency with each ACEs quintile increase with EPDS (76%) contributing most strongly. Findings support the need to move the ACEs paradigm beyond a simple cumulative score when examining effects on early respiratory disease risk. Results also highlight how the impact of early life ACEs varies by ethnoracial identity.

Present study was aimed to elucidate the role of corticotropin releasing hormone (CRH) neurons located in the paraventricular nucleus of the hypothalamus (PVN) in the mechanisms of stress-induced insomnia. Experiments were done in the rodent model of traumatic stress, mice exposure to the predator (rat) odor. Sleep changes associated with this model of stress were first assessed in adult male C57BL/6J wild-type mice (n = 12). The effect of chemogenetic silencing of CRH neurons within the PVN on traumatic stress-induced insomnia was examined in adult male CRH-ires-Cre mice using designer receptors exclusively activated by designer drugs (DREADD) technology. Animals received bilateral injections of inhibitory DREADD vector AAV-hSyn-DIO-hM4Di-mCherry (n = 10) or control AAV-hSyn-DIO-mCherry virus (n = 10) into the PVN during surgery. The DREADD was activated by intraperitoneal injection of clozapine-N-oxide (CNO) prior to the induction of traumatic stress. The exposure of mice to rat odor induced strong long-lasting suppression of both non-rapid eye movement (NREM) and rapid eye movement (REM) sleep stages in both experiments. Selective suppression of CRH neurons within the PVN alleviated acute insomnia by significantly increasing the time spent in NREM sleep but it did not counteract the stress-induced deficit in REM sleep. These findings suggest a specific role for CRH-secreting neurons within the PVN in the suppression of NREM sleep during acute insomnia caused by predator odor stress, whereas REM sleep suppression is controlled by a different mechanism.

Depression commonly accompanies acute coronary syndrome (ACS), impacting up to 30% of patients and correlating with adverse outcomes. Our study aimed to assess the accuracy of clinical impression compared to the PHQ9 questionnaire for evaluating depression in ACS patients admitted to the cardiac intensive care unit. Screening for depression was conducted at least 48 hours from hospital admission and 24 hours following coronary angiography and PCI. The assessment was performed separately and in a blinded manner by the clinical assessment of the attending medical team and by the PHQ9 questionnaire. The study comprised 150 ACS patients with a mean age of 62 ± 13 years. Baseline clinical and demographic characteristics were typical for ACS patients. Based on the PHQ9 questionnaire, depressive symptoms were above the cutoff for clinical depression in 31 (20.7%) patients, with 10 (32.3%) of them experiencing moderate or severe depression (PHQ9 score >15). There were no significant differences in clinical baseline characteristics between the groups with and without clinical depression. Compared to the PHQ9 questionnaire, the medical team’s assessment of depression demonstrated a reasonable specificity of 84% and low sensitivity of 32%. Negative and positive predictive values were 82.6% and 35.8%, respectively. Similar findings were observed in subgroup analyses according to gender, age, type of ACS, and history of cardiovascular disease. Depression is prevalent among ACS patients, highlighting the importance of an increased awareness of this condition. Our findings suggest that detecting clinically significant severity of depressive symptoms by the attending medical team alone may not suffice for depression assessment. Incorporating validated screening tools such as the PHQ9 questionnaire or involving psychological evaluations can enhance the accuracy of depression diagnosis in ACS patients. This multifaceted approach is crucial for ensuring comprehensive care and improving patient outcomes.

Previous studies have shown that corticosterone rapidly alters extracellular serotonin (5-hydroxytryptamine; 5-HT) concentrations in the dorsomedial hypothalamus (DMH) of adult male rats, suggesting a role for corticosterone actions in the DMH in regulation of physiological and behavioral responses. Whether or not corticosterone also rapidly alters extracellular serotonin concentrations in the DMH of female rats, and the dependence of this effect on ovarian hormones, is not known. To determine the effects of 17β-estradiol (E2), progesterone (P), and corticosterone on extracellular concentrations of serotonin in the DMH, corticosterone and/or P were delivered into the DMH of ovariectomized rats via reverse microdialysis in E2-primed rats. Combined, but not separate, delivery of corticosterone and P into the DMH rapidly and transiently increased extracellular 5-HT concentrations, a result that was dependent upon circulating E2. This effect of corticosterone on DMH 5-HT was replicated by local perfusion of the organic cation transporter 3 (OCT3) competitive inhibitor normetanephrine. Intra-DMH infusions of either corticosterone or normetanephrine also reversibly suppressed lordosis responses in E2 + P-primed females. These results suggest that ovarian hormones in combination with corticosterone modulate OCT3-mediated 5-HT clearance in the DMH, potentially representing an adaptive mechanism that allows sexually receptive females to respond rapidly to acute stressors.

Research on stress has demonstrated that the hypothalamic-pituitary-adrenal (HPA) axis contributes to major depressive disorder in youth. Hair glucocorticoids are key biological markers of chronic stress. We assessed group differences in hair cortisol and cortisone concentrations, and the cortisol/cortisone ratio between depressed adolescent women and a non-depressed comparison group. Further, within the depression group, we explored the contribution of symptom severity and clinical correlates of depression in relation to glucocorticoid concentrations. Hair samples of three centimeters for 74 adolescent women (41 in the depression group and 33 in the comparison group), aged between 12 and 19 years old, were analyzed. Depressive and anxiety symptoms were measured using the Beck Youth Inventory II and clinical correlates of depression were measured using the Childhood Trauma Questionnaire–Short Form and the Borderline Personality Features Scale for Children. No significant differences emerged between the depression group and the comparison group on hair cortisol or hair cortisone concentrations. However, groups differed significantly on the cortisol/cortisone ratio, a proposed proxy of 11-beta-hydroxysteroid dehydrogenase activity, with a higher ratio for the depression group. Within the depression group, neither symptom severity nor clinical correlates were associated with glucocorticoid concentrations. Although cross-sectional, our findings highlight the importance of future studies to test whether the group difference found in cortisol/cortisone ratio is the result of alterations in 11-beta-hydroxysteroid dehydrogenase enzymes (type 1 or 2) activity. Further research is thus needed to clarify the role of these enzymes in major depressive disorder in youth and to develop more targeted intervention strategies.

In the current age of technological advancement, stress has emerged as a silent pandemic affecting individuals, especially young generations, globally. Factors such as increased competition, social pressures fueled by social media and smartphones, and a sense of diminished control in the face of modern challenges contribute to rising stress levels. In addition to the negative implications on mental well-being, stress affects physiological processes such as the menstrual cycle. Functional hypogonadotropic hypogonadism is a spectrum ranging ranging from regular menstrual cycles with short or insufficient luteal phases to irregular cycles, oligomenorrhea, anovulation, and complete amenorrhea, depending on how stress variably disrupts gonadotropic-releasing hormone (GnRH) drive. Functional hypothalamic amenorrhea (FHA), the most severe manifestation, is a complex global neuroendocrinopathy with several serious health consequences in addition to amenorrhea and infertility. Concomitant health consequences include bone loss, endothelial dysfunction, and cardiovascular risks. The collective health burden underscores the need for clinical awareness and comprehensive treatment strategies addressing behavioral and biopsychosocial stressors that lead to chronic hypothalamic-pituitary-adrenal (HPA) axis activation. Despite its prevalence and numerous adverse health consequences, research on this condition remains limited, revealing a significant gap in understanding and addressing this condition. Larger and long-term follow-up studies are important to accurately assess FHA prevalence, its health consequences, intervention efficacy, and recovery outcomes.

Recent years brought considerable attention to the connection between chronic stress and the development of autoimmune diseases. However, little is still known about the impact of prolonged stress reactions on the onset and course of primary Sjögren Syndrome (pSS). This study aimed to seek for associations between chronic stress, resulting from stressful life events, and pSS. In the study, 50 patients with diagnosed pSS, as well as 50 control patients with osteoarthritis underwent an assessment. Modified Holmes-Rahe (H-R) stress scale was used in order to evaluate the impact of stressful events within 12 months prior to the diagnosis. Patients with pSS had a significantly higher total score on H-R stress scale within one-year preceding the disease diagnosis (152 ± 66.3 vs 50 ± 54.6; p < 0.001). Additionally, the pSS patients more commonly than the controls reported a subjectively perceived correlation between stressful events and the occurrence of disease symptoms (50% vs 12%; p < 0.001). Moreover, the H-R score at the time of the assessment correlated with the disease activity. The results support the view that pSS belongs to the group of diseases which pathogenesis is closely related to stressful life events. The novelty of this work lies in focus on both the correlation of stress on the onset of autoimmune disease as well as the activity of previously diagnosed disorder. Our data contributes to finding evidence-based medicine (EBM) arguments to what has until recently been merely a thematic observation—the harmfulness of negative stress on individual’s health status.

Previous reports suggest that the menstrual cycle (MC) phases can impact cortisol concentrations. However, research is needed on whether the MC impacts other markers of stress and immune function. It has also been shown that some biomarkers are impacted by time of day, although differences between morning (AM) and afternoon (PM) biomarkers have not been studied over the course of the MC. This study assessed the effect of MC phases and time of day on salivary stress biomarkers [salivary α-amylase (sAA), secretory immunoglobulin A (SIgA)], progesterone, resting blood pressure and resting heart rate (RHR). A single-group repeated measure design was employed in which seventeen participants (n = 17) monitored their MC for two months while attending eight experimental sessions which included both AM and PM sessions during each predicted 1) menses, 2) follicular, 3) ovulatory and 4) luteal phases. Resting blood pressures, heart rates, body composition parameters (assessed via bioelectrical impedance analysis), sAA and SIgA concentrations were assessed. No time of day x MC phase interactions (p > 0.05) were noted for sAA or SIgA, resting blood pressure, heart rate, or body composition parameters. However, sAA and RHR were significantly higher in the PM, while SIgA was significantly higher in the AM. These data suggest that the MC phases do not impact sAA or SIgA, resting blood pressure, heart rates, or body composition parameters. However, time-of-day impacts RHR and concentrations of sAA and SIgA. These findings provide implications for female participants in research dealing with these biomarkers.

Stress occurs as a reaction to mental and emotional pressure, anxiety, or scarring. Chronic stress is defined as constant submission to these moments. It can affect several body systems, increase blood pressure, and weaken immunity, thereby interfering with physiological health processes. Thus, this study aims to evaluate the effects of chronic stress on the redox status and histomorphological parameters of salivary glands. Thirty-two albino Wistar male rats were randomly divided into two groups: chronic stress and control. Chronically stressed animals were subjected to a restraint protocol by introducing them into a polyvinyl tube for 4 hours daily for 28 days, allowing immobilization of their movements. Subsequently, the animals were euthanized for further collection of the parotid and submandibular salivary glands. The redox state of the glands was evaluated using the antioxidant capacity against peroxyl radicals (ACAP) and thiobarbituric acid reactive substances (TBARS) assays. Histological analysis was performed through morphometry of the tissues stained with hematoxylin and eosin and histochemical through picrosirius red staining. Both the parotid and submandibular glands of stressed rats exhibited oxidative stress due to a decrease in ACAP and an increase in TBARS levels. However, the parotid glands are more susceptible to harmful changes in the tissue, such as an increase in the stromal area and in the collagen area fraction, decrease in the acinar area, and smaller size of the acinus and ducts. Our results suggest that chronic stress may cause harmful modulation of the redox state of the salivary glands, with different histological repercussions.

Chronic stress and stress-related mental illnesses such as major depressive disorder (MDD) constitute some of the leading causes of disability worldwide with a higher prevalence in women compared to men. However, preclinical research into stress and MDD is heavily biased toward using male animals only. Aberrant activity of the hypothalamic-pituitary-adrenal (HPA) axis has been linked to the development of MDD and several animal models of MDD have been established based on HPA axis dysregulation. In the present study, we compared stress biomarkers and behavior of male and female mice after acute and chronic restraint stress to investigate potential effects of sex differences in the stress response. Further, the validity of the interrupted repeated restraint stress (IRRS) model as an animal model for the HPA axis disturbances seen in MDD was assessed. After acute stress, female mice showed increased corticosterone secretion and changes in molecular markers suggesting increased HPA axis feedback sensitivity. Acute stress-induced signs of anxiety-like behavior were observed in male mice only suggesting that female mice may be more resilient to the anxiogenic effects of acute stress. Males and females responded similarly to IRRS with no sustained perturbations in HPA axis biomarkers. The IRRS model did not adequately translate to the changes reported in MDD with HPA axis overactivity and more severe perturbation models are likely needed. However, in alignment with previous studies, these data support that there are important sex differences in the HPA axis and that these may contribute to the etiology of stress-related psychiatric disorders.

Background Self-reported mental stress is not consistently recognized as a risk factor for stroke. This prompted development of a novel algorithm for stress-phenotype indices to quantify chronic stress prevalence in relation to a modified stroke risk score in a South African cohort. The algorithm is based on biomarkers adrenocorticotrophic hormone, high-density lipoprotein cholesterol, high-sensitive cardiac-troponin-T, and diastolic blood pressure which exemplifies the stress-ischemic-phenotype index. Further modification of the stroke risk score to accommodate alcohol misuse established the stress-diabetes-phenotype index. Whether positive stress-phenotype individuals will demonstrate a higher incidence of stroke in an independent Swedish cohort was unknown and investigated. Methods Stress-phenotyping was done at baseline for 50 participants with incident stroke and 100 age-, and sex matched controls (aged 76 ± 5 years) from 2,924 individuals in southern Sweden. The mean time from inclusion to first stroke event was 5 ± 3 years. Stress-phenotyping comparisons and stroke incidence risk were determined. Results A positive stress-ischemic-phenotype reflected higher incident stroke (72% vs. 28%, p = 0.019) and mortality rates (41% vs. 23%, p = 0.019). Whereas a positive stress-diabetes-phenotype reflected a higher incident stroke rate (80% vs. 20%, p = 0.008) but similar mortality rate (38% vs. 25%, p = 0.146). Both the positive stress-ischemic (OR: 2.9, 95% CI: 1.3–6.5, p = 0.011) and stress-diabetes-phenotypes (OR: 3.7, 95% CI: 1.5–8.9, p = 0.004) showed large effect size associations with incident stroke independent of cardiovascular risk confounders. Conclusion Positive stress-phenotype indices demonstrated a higher incidence of stroke. Ultimately the Malan stress-phenotype algorithms developed in South Africa could confirm incident stroke in an independent Swedish cohort. Stress-phenotyping could thus be useful in clinical routine practice in order to detect individuals at higher stroke risk.

Burnout is caused by long term psychosocial stress and has, besides the fatigue and mental health burden, been associated with increased risk of adverse physical health, such as for example type 2 diabetes. This study aims to investigate the glucose and insulin levels in individuals with stress related burnout, by assessing these metabolic markers in response to a standard oral glucose tolerance test (OGTT). 38 cases with burnout (13 men and 25 women) and 35 healthy controls (13 men and 22 women) in the age 24–55 were included in the study. The burnout group overall did not differ from healthy controls in glucose or insulin levels during the OGTT. However, the burnout cases who reported more severe burnout symptoms exhibited significantly higher levels of both glucose and insulin levels during the OGTT compared to burnout cases reporting lower severity of symptoms. Furthermore, the group of burnout cases who reported symptoms of depression exhibited higher insulin levels during OGTT compared to the burnout cases without depressive symptoms. The observed higher levels in the burnout cases with most severe symptoms indicate an increased diabetic risk in these patients and it may be of importance to follow glucose and insulin levels in individuals with more severe symptoms of burnout i.e. to perform an OGTT.

Background Investigations of maternal psychosocial stress and child asthma have produced mixed findings, which may reflect inconsistent consideration of modifying factors. Objective To examine associations between maternal lifetime stress and child asthma, and to assess effect modification by maternal pre-pregnancy body mass index and race/ethnicity in a prenatal cohort of mother-child dyads. Methods Maternal lifetime stress was assessed using the Life Stressor Checklist-Revised, administered during pregnancy and child asthma was ascertained by parent-report in study follow-up visits. In the overall group and stratified by race/ethnicity, we used multivariable logistic regression and varying coefficient modeling to investigate the association between maternal stress and child asthma, assessing for effect modification by pre-pregnancy body mass index. Results Women were predominately Black (Black/Hispanic-Black 44.5%) or non-Black Hispanic (37.6%), with elevated pre-pregnancy body mass index (25.1% overweight, 29.8% obese); 17% of children had asthma. Higher maternal stress was associated with increased relative odds of child asthma only in dyads with women in the obese (≥30 kilograms/meters squared) category (odds ratio 1.84, 95% confidence interval 1.27-2.67). Varying coefficient models demonstrated stronger positive associations between increased maternal lifetime stress and child asthma in women with higher pre-pregnancy body mass index; the strongest association was observed in the Black group. Conclusion Maternal pre-pregnancy body mass index modified the association between maternal lifetime stress and child asthma. These findings underscore the need to consider complex interactions to fully elucidate intergenerational stress effects on early childhood asthma.

Adverse Childhood Experiences (ACEs) are very common and presently implicated in 9 out of 10 leading causes of death in the United States. Despite this fact, our mechanistic understanding of how ACEs impact health is limited. Moreover, interventions for reducing stress presently use a one-size-fits-all approach that involves no treatment tailoring or precision. To address these issues, we developed a combined cross-sectional study and randomized controlled trial, called the California Stress, Trauma, and Resilience Study (CalSTARS), to (a) characterize how ACEs influence multisystem biological functioning in adults with all levels of ACE burden and current perceived stress, using multiomics and other complementary approaches, and (b) test the efficacy of our new California Precision Intervention for Stress and Resilience (PRECISE) in adults with elevated perceived stress levels who have experienced the full range of ACEs. The primary trial outcome is perceived stress, and the secondary outcomes span a variety of psychological, emotional, biological, and behavioral variables, as assessed using self-report measures, wearable technologies, and extensive biospecimens (i.e. DNA, saliva, blood, urine, & stool) that will be subjected to genomic, transcriptomic, proteomic, metabolomic, lipidomic, immunomic, and metagenomic/microbiome analysis. In this protocol paper, we describe the scientific gaps motivating this study as well as the sample, study design, procedures, measures, and planned analyses. Ultimately, our goal is to leverage the power of cutting-edge tools from psychology, multiomics, precision medicine, and translational bioinformatics to identify social, molecular, and immunological processes that can be targeted to reduce stress-related disease risk and enhance biopsychosocial resilience in individuals and communities worldwide.

It is well-established that disrupted autonomic nervous system (ANS) reactivity exacerbates risk for long-term maladjustment following childhood adversity (CA). However, few studies have integrated measures of both the sympathetic (SNS) and parasympathetic (PNS) branches of the ANS, resulting in a unidimensional understanding of ANS functioning as a mechanism of risk. Further, past work has primarily measured CA only at the aggregate level (e.g. “total CA”), necessitating further research to accurately characterize this risk pathway. The present study examines how CA, measured cumulatively and dimensionally (i.e. CA characterized by threat versus deprivation), moderates the association between the SNS and PNS at rest and in response to acute social and nonsocial stressors. Participants included 97 adolescents ages 10-15 (Mage = 12.22, SDage = 1.68) experiencing a range of CA and one accompanying caregiver. Participants completed questionnaires assessing prior CA exposure. SNS and PNS responses were then continuously measured during rest and two stress tasks. First, results indicate a blunting effect of cumulative CA and CA characterized by threat (e.g. physical abuse) on resting SNS activity. Second, in moderation analyses assessing ANS coordination, threat exposure emerged as a significant moderator of the association between SNS and PNS reactivity to social stress. Results suggest that CA characterized by threat may specifically impact physiologic regulation by disrupting the coordination of the two branches of the ANS. Disentangling the independent and concurrent engagement of biological stress response systems following CA remains an important target for research to identify the etiology of aberrant stress reactivity patterns.

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.

The main aim of this review is to compare whether natural sounds or a quiet environment is more beneficial for alleviating stress. The results showed that there is a statistically significant difference between exposure to natural sounds and a quiet environment in terms of their effect on heart rate (p = 0.006), blood pressure (p = 0.001), and respiratory rate (p = 0.032). However, no significant difference was found between exposure to natural sounds and a quiet environment in terms of their effect on MAP (p = 0.407), perceived stress, and SPO2 (p = 0.251). Although the evidence was slightly inconsistent, overall, natural sounds were found more beneficial for stress reduction than quiet environments.

Laboratory stress tasks are necessary to closely investigate the stress response in a controlled environment. However, to our knowledge, no study has tested whether participating in such tasks can pose any daily life adverse effect. Fifty-three healthy participants (46 women) took part in a laboratory session where stress was induced using a typical psychosocial stressor: the repeated Montreal Imaging Stress Task (rMIST). Average levels of negative affect (NA), heart rate (HR), root mean square of successive differences (RMSSD), and skin conductance level (SCL), as well as reactivity across all these parameters as measured with the experience sampling method (ESM) in the four days prior to the laboratory session were compared with the four days following the session. We also assessed whether vulnerability to psychopathology moderated these associations. Findings showed that the task did not pose any significant adverse effect on participants. However, there was an unexpected increase in average RMSSD and a decrease in average SCL pre- to post- task. In addition, more vulnerable individuals were more likely to experience an increase in average levels of NA in the days following the task compared to the days preceding it. Our findings suggest that laboratory stress tasks may pose a significant risk to more vulnerable individuals.

Aberrant functioning of the hypothalamic-pituitary-adrenal (HPA) axis is a hallmark of conditions such as depression, anxiety disorders, and post-traumatic stress disorder. Early-life adversity and genetic variation can interaction to disrupt HPA axis regulation, potentially contributing to certain forms of psychopathology. This study employs a rhesus macaque model to investigate how early parental neglect interacts with a single nucleotide polymorphism within the promoter region of the corticotropin-releasing hormone (CRH-248) gene, impacting the development of the HPA axis. For the initial six months of life, 307 rhesus monkey infants (n = 146 females, n = 161 males) were either reared with their mothers (MR) in conditions emulating the natural environment (control group) or raised without maternal care in groups with constant or 3-hours daily access to same-aged peers (NR). Blood samples collected on days 30, 60, 90, and 120 of life under stressful conditions were assayed for plasma cortisol and adrenocorticotropic hormone (ACTH) concentrations. Findings revealed that NR subjects exhibited a significant blunting of both ACTH and cortisol concentrations. Notably, there was a gene-by-environment interaction observed for ACTH and cortisol levels, with NR subjects with the polymorphism displaying higher ACTH concentrations and lower cortisol concentrations. To the extent that these results generalize to humans, they suggest that early parental neglect may render individuals vulnerable to HPA axis dysfunction, a susceptibility that is modulated by CRH-248 genotype—a gene-by-environment interaction that leaves a lasting developmental signature.

Sense of Okayness (SOK) is an emerging concept that describes a person’s ability to remain stable and unshaken in the face of life transitions and hardships. This quality enables effective stress regulation and heightened tolerance to uncertainty. To investigate the possible role of the parasympathetic nervous system (PNS) in mediating the relationship between SOK and stress regulation among older individuals, an analytical sample of N = 69 participants (74% women) with a mean age of 78.75 years (SD age = 6.78) was recruited for a standardized cognitive assessment and stress induction. Baseline heart rate variability (HRV), measured via electrocardiogram (ECG), and SOK assessments were conducted prior to stress induction, along with a baseline cognitive evaluation. Subsequently, participants were subjected to a psychosocial stress paradigm, followed by either a 30-minute SOK elevation intervention (n = 40) or a control condition with nature sounds (n = 29). A second cognitive assessment was administered post-intervention, with continuous HRV measurement through ECG. The results revealed significant HRV changes due to the experimental intervention, though no significant differences were observed between the SOK intervention and control groups. Interestingly, individuals with high trait SOK displayed more stable HRV trajectories, exhibiting a smaller decline during the stress intervention and a milder increase during both the stressor and SOK intervention phases. Overall, these findings do suggest a significant association between SOK, parasympathetic activity, and stress reactivity. These results prompt further investigation into whether personality patterns, such as a strong SOK, may be linked to reduced vagal reactivity and better coping in old age.

Ingestion of L-theanine and L-tyrosine has been shown to reduce salivary stress biomarkers and improve aspects of cognitive performance in response to stress. However, there have been no studies to concurrently examine the impact of both L-theanine and L-tyrosine ingestion during a mental stress challenge (MSC) involving a brief cognitive challenge and a virtual reality based active shooter training drill. Thus, the purpose of this study was to determine the impact of ingestion of L-theanine and L-tyrosine on markers of stress and cognitive performance in response to a virtual reality active shooter drill and cognitive challenge. The cognitive challenge involved a Stroop challenge and mental arithmetic. Eighty subjects (age = 21 ± 2.6 yrs; male = 46; female = 34) were randomly assigned L-tyrosine (n = 28; 2000 mg), L-theanine (n = 25; 200 mg), or placebo (n = 27) prior to MSC exposure. Saliva samples, state-anxiety inventory (SAI) scales, and heart rate (HR) were collected before and after exposure to the MSC. Saliva was analyzed for stress markers α-amylase (sAA) and secretory immunoglobulin A (SIgA). The MSC resulted in significant increases in sAA, SIgA, HR, and SAI. Ingestion of L-theanine and L-tyrosine did not impact markers of stress. However, the L-tyrosine treatment demonstrated significantly lower missed responses compared to the placebo treatment group during the Stroop challenge. These data demonstrate that ingestion of L-theanine or L-tyrosine does not impact markers of stress in response to a MSC but may impact cognitive performance. This study was pre-registered as a clinical trial ("Impact of supplements on stress markers”: NCT05592561).

Stress has been linked to the development of irritable bowel syndrome (IBS), and various methods have been explored to model IBS in combination with other stimuli. However, it remains unclear whether stress alone can induce IBS in animals. This study aimed to investigate the impact of chronic unpredictable mild stress (CUMS) on gastrointestinal sensation and function in mice and assess the potential of CUMS as a modeling approach for IBS. To evaluate the mice’s behavior, we conducted open field test, sucrose preference test and weighed the mice, revealing that CUMS indeed induced anxiety and depression in the mice and caused weight loss. Further analyses, including fecal analysis, a total gastrointestinal transport test, and a colon propulsion test, demonstrated that CUMS led to abnormal defecation and disruptions in gastrointestinal motility in the mice. Additionally, the abdominal withdrawal reflex test indicated an increase in visceral sensitivity in CUMS-exposed mice. Histological examination using hematoxylin and eosin staining revealed no significant histological alterations in the colons of CUMS-exposed mice, but it did show a minor degree of inflammatory cell infiltration. In summary, the findings suggest that CUMS can replicate IBS-like symptoms in mice, offering a novel top-down approach to modeling IBS.

Chronic stress leads to hypofunction of the medial prefrontal cortex (mPFC), mechanisms of which remain to be determined. Enhanced activation of GABAergic of parvalbumin (PV) expressing interneurons (INs) is thought to play a role in stress-induced prefrontal inhibition. In this study, we tested whether chemogenetic inhibition of mPFC PV INs after chronic stress can rescue chronic stress-related behavioral and physiological phenotypes. Mice underwent 2 weeks of chronic variable stress (CVS) followed by a battery of behavioral tests known to be affected by chronic stress exposure, e.g. an open field (OF), novel object recognition (NOR), tail suspension test (TST), sucrose preference test (SPT), and light dark (LD) box. Inhibitory DREADDs were actuated by 3 mg/kg CNO administered 30 min prior to each behavioral test. CVS caused hyperactivity in the OF, reduced sucrose preference in the SPT (indicative of enhanced anhedonia), and increased anxiety-like behavior in the LD box. Inhibition of PV IN after stress mitigated these effects. In addition, CVS also resulted in reduced thymus weight and body weight loss, which were also mitigated by PV IN inhibition. Our results indicate that chronic stress leads to plastic changes in PV INs that may be mitigated by chemogenetic inhibition. Our findings implicate cortical GABAergic INs as a therapeutic target in stress-related diseases.

Dehydroepiandrosterone (DHEA) and cortisol release appear to have contrasting effects on stress perception during stressful tasks. This study aimed to investigate anticipatory examination stress in college students by considering DHEA, cortisol, psycho-emotional aspects and examination performance. Seventy-six students (66 females, 10 males; age range 18–25 years) provided saliva samples and completed questionnaires in two sessions 48 hours apart. During the second session, the students performed the examination. The questionnaires used were the State-Trait Anxiety Inventory, the Positive and Negative Affect Scale, and the Brief-Coping Orientation to Problems Experienced Inventory. DHEA, cortisol, anxiety and negative affect showed an anticipatory rise before the examination (all ps < 0.001). This rise of DHEA and cortisol was associated with lower positive affect (p = 0.001 and p = 0.043, respectively). However, only the DHEA anticipatory levels were linked to poorer examination marks (p = 0.020). Higher levels of the DHEA/cortisol ratio in anticipation of the examination were related to lower scores on the support-seeking strategy (p = 0.022). There was no association between DHEA and cortisol levels and anxiety, negative affect, active and avoidant coping strategies, or academic record. These results suggest that how DHEA and cortisol respond in anticipation of examination stress significantly impacts students’ emotional well-being during examination periods and how they cope with stress. They also suggest that levels of DHEA in anticipation of an academic stressor have detrimental effects on stress management.