Sympathetic-adrenal-medullary Research Articles

Exploring the interplay between stress mediators and skin microbiota in shaping age-related hallmarks: A review

Psychological stress is a major contributing factor to several health problems (e.g., depression, cardiovascular disease). Around 35 % of the world’s population suffers from it, including younger generations. Physiologically, stress manifests through neuroendocrine pathways (Hypothalamic-Pituitary-Adrenal (HPA) axis and Sympathetic-Adrenal-Medullary (SAM) system) which culminate in the production of stress mediators like cortisol, epinephrine and norepinephrine. Stress and its mediators have been associated to body aging, through molecular mechanisms such as telomere attrition, mitochondrial dysfunction, cellular senescence, chronic inflammation, and dysbiosis, among others. Regarding its impact in the skin, stress impacts its structural integrity and physiological function. Despite this review focusing on several hallmarks of aging, emphasis was placed on skin microbiota dysbiosis. In this line, several studies, comprising different age groups, demographic contexts and body sites, have reported skin microbiota alterations associated with aging, and some effects of stress mediators on skin microbiota have also been reviewed in this paper. From a different perspective, since it is not a “traditional” stress mediator, oxytocin, a cortisol antagonist, has been related to glucorticoids inhibition and to display positive effects on cellular aging. This hormone dysregulation has been associated to psychological issues such as depression, whereas its upregulation has been linked to positive social interaction.

Surface temperatures are influenced by handling stress independently of corticosterone levels in wild king penguins (Aptenodytes patagonicus)

Assessing the physiological stress responses of wild animals opens a window for understanding how organisms cope with environmental challenges. Since stress response is associated with changes in body temperature, the use of body surface temperature through thermal imaging could help to measure acute and chronic stress responses non-invasively. We used thermal imaging, acute handling-stress protocol and an experimental manipulation of corticosterone (the main glucocorticoid hormone in birds) levels in breeding king penguins (Aptenodytes patagonicus), to assess: 1. The potential contribution of the Hypothalamo-Pituitary-Adrenal (HPA) axis in mediating chronic and acute stress-induced changes in adult surface temperature, 2. The influence of HPA axis manipulation on parental investment through thermal imaging of eggs and brooded chicks, and 3. The impact of parental treatment on offspring thermal's response to acute handling.Maximum eye temperature (Teye) increased and minimum beak temperature (Tbeak) decreased in response to handling stress in adults, but neither basal nor stress-induced surface temperatures were significantly affected by corticosterone implant. While egg temperature was not significantly influenced by parental treatment, we found a surprising pattern for chicks: chicks brooded by the (non-implanted) partner of corticosterone-implanted individuals exhibited higher surface temperature (both Teye and Tbeak) than those brooded by glucocorticoid-implanted or control parents. Chick's response to handling in terms of surface temperature was characterized by a drop in both Teye and Tbeak independently of parental treatment.We conclude that the HPA axis seems unlikely to play a major role in determining chronic or acute changes in surface temperature in king penguins. Changes in surface temperature may primarily be mediated by the Sympathetic-Adrenal-Medullary (SAM) axis in response to stressful situations. Our experiment did not reveal a direct impact of parental HPA axis manipulation on parental investment (egg or chick temperature), but a potential influence on the partner's brooding behaviour.

Stress biomarkers and child development in young children in Bangladesh

BackgroundHundreds of millions of children in low- and middle-income countries are exposed to chronic stressors, such as poverty, poor sanitation and hygiene, and sub-optimal nutrition. These stressors can have physiological consequences for children and may ultimately have detrimental effects on child development. This study explores associations between biological measures of chronic stress in early life and developmental outcomes in a large cohort of young children living in rural Bangladesh. MethodsWe assessed physiologic measures of stress in the first two years of life using measures of the hypothalamic-pituitary-adrenal (HPA) axis (salivary cortisol and glucocorticoid receptor gene methylation), the sympathetic-adrenal-medullary (SAM) system (salivary alpha-amylase, heart rate, and blood pressure), and oxidative status (F2-isoprostanes). We assessed child development in the first two years of life with the MacArthur-Bates Communicative Development Inventories (CDI), the WHO gross motor milestones, and the Extended Ages and Stages Questionnaire (EASQ). We compared development outcomes of children at the 75th and 25th percentiles of stress biomarker distributions while adjusting for potential confounders using generalized additive models, which are statistical models where the outcome is predicted by a potentially non-linear function of predictor variables. ResultsWe analyzed data from 684 children (49% female) at both 14 and 28 months of age; we included an additional 765 children at 28 months of age. We detected a significant relationship between HPA axis activity and child development, where increased HPA axis activity was associated with poor development outcomes. Specifically, we found that cortisol reactivity (coefficient −0.15, 95% CI (−0.29, −0.01)) and post-stressor levels (coefficient −0.12, 95% CI (−0.24, −0.01)) were associated with CDI comprehension score, post-stressor cortisol was associated with combined EASQ score (coefficient −0.22, 95% CI (−0.41, −0.04), and overall glucocorticoid receptor methylation was associated with CDI expression score (coefficient −0.09, 95% CI (−0.17, −0.01)). We did not detect a significant relationship between SAM activity or oxidative status and child development. ConclusionsOur observations reveal associations between the physiological evidence of stress in the HPA axis with developmental status in early childhood. These findings add to the existing evidence exploring the developmental consequences of early life stress.

The Interplay of Stress and Salivary Cortisol Saliva in Multibacillary Leprosy: A Cross-Sectional Analysis in South Sulawesi, Indonesia

Background: Leprosy remains a significant health concern in Indonesia, particularly in South Sulawesi, where the prevalence rate has reached 0,78 per 10,000 population. The increasing number of new cases, mainly of the multibacillary type, poses a serious epidemiological and clinical challenge. Leprosy patients often face social stigma, leading them to live in isolation, causing additional stress for the patients. Stress triggers various physiological responses, including the activation of the hypothalamic-pituitary-adrenal (HPA) axis and sympathetic-adrenal-medullary (SAM) system. Cortisol, the primary glucocorticoid secreted by the adrenal cortex, is the end product of the HPA axis. In the salivary glands, cortisol exists only in its active form, different from its presence in the serum. Objective: To analyze salivary cortisol levels and correlate them with the stress scale in multibacillary leprosy patients Methods: This study used a descriptive-analytic approach with a cross-sectional method. Twenty-five samples in Makassar from November 2022 to January 2023, with the criteria of those newly diagnosed with multi-bacillary leprosy based on clinical and laboratory examination, participated. The stress scale was assessed with the Perceived Stress Scale-10 (PSS-10). Using enzyme-linked immunosorbent assay (ELISA) to measure saliva cortisol levels. Result: The correlation for the stress scale with the cortisol saliva levels shows a negative correlation with salivary cortisol levels in this study showing a mean value of 67,76 ng/ml and a significance value of 0.000. Conclusion: There is a negative correlation between stress scale and salivary cortisol levels. The more severe the stress, the lowest cortisol saliva level

Spiritual Meaning Impacts Psychological Distress and Control of Mean Arterial Pressure in Hypertension Patients

Hypertension is a disease that can cause various complications and is made worse by psychological distress, where cases are increasing at the Bangkalan Community Health Center. This research aims to analyze the correlation between spiritual meaning in regulating psychological distress and mean arterial pressure (MAP) in hypertension patients. This research method is correlation analytic with a cross-sectional approach with the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guideline. population of 76 patients and a sample of 62 taken using simple random sampling. The independent variable is spiritual meaning, measured using the Daily Spiritual Experience Scale (DSES). Meanwhile, the dependent variable is distress, measured by the Kessler Psychological Distress Scale and the mean arterial pressure (MAP) value. The collected data was then subjected to statistical tests using Spearman ranks with an alpha value of 0.05. The research results show a relationship between spiritual meaning and psychological distress with a p-value of 0.016 < 0.05 and a correlation coefficient of -0.305. Spirituality is also significantly related to the mean arterial pressure (MAP) value with p value 0.005 < 0.05, and the correlation coefficient is -0.351. Spirituality has an impact on reducing psychological distress, affecting the function of the Hypothalamus Pituitary Adrenal (HPA) Axis and Sympathetic Adrenal Medullary (SAM) Axis. The SAM Axis will balance the secretion of norepinephrine (NE) and epinephrine (E), which affects the balance of contraction of smooth cardiac muscle cells, vasoconstriction and vasodilation, heart rate, and normalizes sodium levels so that it can control blood pressure in hypertensive patients.

The HPA and SAM axis mediate the impairment of creativity under stress.

With the ever-changing social environment, individual creativity is facing a severe challenge induced by stress. However, little is known regarding the underlying mechanisms by which acute stress affects creative cognitive processing. The current research explored the impacts of the neuroendocrine response on creativity under stress and its underlying cognitive flexibility mechanisms. The enzyme-linked immuno sorbent assay was employed to assess salivary cortisol, which acted as a marker of stress-induced activation of the hypothalamic-pituitary-adrenal (HPA) axis. Eye blink rate (EBR) and pupil diameter were measured as respective indicators of dopamine and noradrenaline released by the activation of the sympathetic-adrenal-medullary (SAM) axis. The Wisconsin card task (WCST) measured cognitive flexibility, while the alternative uses task (AUT) and the remote association task (RAT) measured separately divergent and convergent thinking in creativity. Results showed higher cortisol increments following acute stress induction in the stress group than control group. Ocular results showed that the stress manipulation significantly increased EBR and pupil diameter compared to controls, reflecting increased SAM activity. Further analysis revealed that stress-released cortisol impaired the originality component of the AUT, reducing cognitive flexibility as measured by perseverative errors on the WCST task. Serial mediation analyses showed that both EBR and pupil diameter were also associated with increased perseverative errors leading to poor originality on the AUT. These findings confirm that physiological arousal under stress can impair divergent thinking through the regulation of different neuroendocrine pathways, in which the deterioration of flexible switching plays an important mediating role.

It's cool to be stressed: Body surface temperatures track sympathetic nervous system activation during acute stress.

The acute stress response can be considered the primary evolutionary adaptation to maximise fitness in the face of unpredictable environmental challenges. However, the difficulties of assessing physiology in natural environments mean comparatively little is known about how response variation influences fitness in free-living animals. Currently, determining acute stress physiology typically involves blood sampling or cardiac monitoring. Both require trapping and handling, interrupting natural behaviour, and potentially biasing our understanding toward trappable species/individuals. Importantly, limits on repeated sampling also restrict response phenotype characterisation, vital for linking stress with fitness. Surface temperature dynamics resulting from peripheral vasomotor activity during acute stress are increasingly promoted as alternative physiological stress indicators, which can be measured non-invasively using infrared thermal imaging, overcoming many limitations of current methods. Nonetheless, which aspects of stress physiology they represent remains unclear, as the underlying mechanisms are unknown. To date, validations have primarily targeted the hypothalamic-pituitary-adrenal axis, when the sympathetic-adrenal-medullary (SAM) system is likely the primary driver of vasomotor activity during acute stress. To address this deficit, we compared eye and bill region surface temperatures - measured using thermal imaging - with SAM system activity - measured as heart-rate-variability via electrocardiogram telemetry - in wild-caught captive house sparrows (Passer domesticus), during capture and handling. We found lower body surface temperatures were associated with increased sympathetic nervous system activation. Consequently, our data confirm body surface temperatures can act as a proxy for sympathetic activation during acute stress, providing potentially transformative opportunities for linking the acute stress response with fitness in the wild.

0131 Sleep Deprivation Alters Two Physiological Systems' Responses to Repeated Stressors Differentially

Abstract Introduction The hypothalamic-pituitary-adrenal (HPA) and sympathetic-adrenal-medullary (SAM) axes activate in response to stressors. Real-world exposure to stressors often co-occurs with total sleep deprivation (TSD). The SAM response to a single stressor appears unchanged by TSD, but salivary alpha-amylase (sAA) has shown that TSD blunts the SAM response to repeated stressor exposure. Using salivary cortisol concentration (SCC), we investigated the HPA response to repeated stressors under well-rested and TSD conditions. Methods N=10 healthy adults (ages 28.3±5.78; 5f) completed a 4-day/3-night in-laboratory study with 38h TSD preceded and followed by 10h sleep opportunities. On day 2 (well-rested) and day 3 (TSD), participants completed two stressor sessions in a high-fidelity shooting simulator, separated by 30min. Acting as police officers, civilian participants verbally interacted with emergency response scenarios and decided whether to use (simulated) deadly force. Seven saliva samples were collected each day: pre-stressor, and 0min, 15min, and 30min after each session. Samples were assayed for SCC and normalized against each day’s pre-stressor sample. Results Mixed-effects ANOVA showed a significant effect of sample time (F[5,99]=19.85, p< 0.001), with SCC peaking 15min after the first stressor session and steadily declining thereafter. The SCC peak was significantly blunted during TSD compared to well-rested (t[99]=2.84, p=0.006). Correlations with previously reported, simultaneously assessed sAA concentrations, which peaked right after the first stressor session, were not significant (p>0.2). Additionally, whereas sAA showed a second peak after the second stressor session when participants were well-rested, no second peak was found in SCC. Conclusion The SCC response after one stressor session with simulated emergency response scenarios was blunted during TSD, unlike the sAA response. However, while sAA peaked twice in response to repeated stressor exposure when participants were well-rested (though not during TSD), SCC continued to decline after the first stressor exposure, potentially indicating a HPA refractory mechanism or habituation. Also, over participants there was no significant relationship between the magnitude of the stressor response between SCC and sAA. Taken together, our results suggest fundamentally distinct SAM and HPA axis responsivity to repeated acute stressors, with differential impact of TSD. Support (if any) ONR N00014-13-1-0302, PRMRP W81XWH-20-1-0442.

Vulnerability to chronic stress and the phenotypic heterogeneity of presbycusis with subjective tinnitus.

Age-related functional reserve decline and vulnerability of multiple physiological systems and organs, as well as at the cellular and molecular levels, result in different frailty phenotypes, such as physical, cognitive, and psychosocial frailty, and multiple comorbidities, including age-related hearing loss (ARHL) and/or tinnitus due to the decline in auditory reserve. However, the contributions of chronic non-audiogenic cumulative exposure, and chronic audiogenic stress to phenotypic heterogeneity of presbycusis and/or tinnitus remain elusive. Because of the cumulative environmental stressors throughout life, allostasis systems, the hypothalamus-pituitary-adrenal (HPA) and the sympathetic adrenal-medullary (SAM) axes become dysregulated and less able to maintain homeostasis, which leads to allostatic load and maladaptation. Brain-body communication via the neuroendocrine system promotes systemic chronic inflammation, overmobilization of energetic substances (glucose and lipids), and neuroplastic changes via the non-genomic and genomic actions of glucocorticoids, catecholamines, and their receptors. These systemic maladaptive alterations might lead to different frailty phenotypes and physical, cognitive, and psychological comorbidities, which, in turn, cause and exacerbate ARHL and/or tinnitus with phenotypic heterogeneity. Chronic audiogenic stressors, including aging accompanying ontological diseases, cumulative noise exposure, and ototoxic drugs as well as tinnitus, activate the HPA axis and SAM directly and indirectly by the amygdala, promoting allostatic load and maladaptive neuroplasticity in the auditory system and other vulnerable brain regions, such as the hippocampus, amygdala, and medial prefrontal cortex (mPFC). In the auditory system, peripheral deafferentation, central disinhibition, and tonotopic map reorganization may trigger tinnitus. Cross-modal maladaptive neuroplasticity between the auditory and other sensory systems is involved in tinnitus modulation. Persistent dendritic growth and formation, reduction in GABAergic inhibitory synaptic inputs induced by chronic audiogenic stresses in the amygdala, and increased dendritic atrophy in the hippocampus and mPFC, might involve the enhancement of attentional processing and long-term memory storage of chronic subjective tinnitus, accompanied by cognitive impairments and emotional comorbidities. Therefore, presbycusis and tinnitus are multisystem disorders with phenotypic heterogeneity. Stressors play a critical role in the phenotypic heterogeneity of presbycusis. Differential diagnosis based on biomarkers of metabonomics study, and interventions tailored to different ARHL phenotypes and/or tinnitus will contribute to healthy aging and improvement in the quality of life.

A randomized pilot study of the prophylactic effect of ketamine on laboratory-induced stress in healthy adults

BackgroundStress exposure is a key risk factor for the development of major depressive disorder and posttraumatic stress disorder. Enhancing stress resilience in at-risk populations could potentially protect against stress-induced disorders. The administration of ketamine one week prior to an acute stressor prevents the development of stress-induced depressive-like behavior in rodents. This study aimed to test if the prophylactic effect of ketamine against stress also applies to humans. MethodsWe conducted a double-blind, placebo-controlled study wherein 24 healthy subjects (n = 11 males) were randomized to receive either ketamine (0.5 mg/kg) or midazolam (0.045 mg/kg) intravenously one week prior to an acute stress [Trier Social Stress Test (TSST)]. The primary endpoint was the anxious-composed subscale of the Profile of Mood States Bipolar Scale (POMS-Bi) administered immediately after the TSST. Salivary and plasma cortisol and salivary alpha amylase were also measured at 15-min intervals for 60 min following the stressor, as proxies of hypothalamic pituitary adrenal (HPA) and sympathetic-adrenal-medullary (SAM) axis activity, respectively. ResultsCompared to the midazolam group (n = 12), the ketamine group (n = 12) showed a moderate to large (Cohen's d = 0.7) reduction in levels of anxiety immediately following stress, although this was not significant (p = 0.06). There was no effect of group on change in salivary cortisol or salivary alpha amylase following stress. We conducted a secondary analysis excluding one participant who did not show an expected correlation between plasma and salivary cortisol (n = 23, ketamine n = 11). In this subgroup, we observed a significant reduction in the level of salivary alpha amylase in the ketamine group compared to midazolam (Cohen's d = 0.7, p = 0.03). No formal adjustment for multiple testing was made as this is a pilot study and all secondary analyses are considered hypothesis-generating. ConclusionsKetamine was associated with a numeric reduction in TSST-induced anxiety, equivalent to a medium-to-large effect size. However, this did not reach statistical significance . In a subset of subjects, ketamine appeared to blunt SAM reactivity following an acute stressor. Future studies with larger sample size are required to further investigate the pro-resilient effect of ketamine.

MANAGEMENT OF ULCERATIVE ORAL LICHEN PLANUS PREDISPOSED BY PSYCHOLOGICAL STRESS

Background: Oral lichen planus (OLP) is a chronic inflammatory autoimmune oral mucosa disease. The ulcerative type of OLP presents as erythematous ulceration with mucosal erosions surrounding whitish striae. The aetiology of OLP is unknown, but can be predisposed by psychological factors. Purpose: Reporting ulcerative oral lichen planus predisposed by psychological stress. Case: A 36 years old woman complained very painful ulcer in the right buccal mucosa and a grey-purple lower lip lesion for a year. It had been treated with topical corticosteroids, antibiotics, tretinoin, and vitamins but did not heal. Extraoral examination on the lower vermillion showed bluish-purple macules, diffuse and irregular borders, rough and painful. Intraoral examination in the right buccal mucosa showed an irregular yellowish-white ulcer with an erythematous area and white striae. Case Management: Screening for psychological stress by DASS 42 showed moderate stress and severe anxiety. Autofluorescence examination showed no malignant transformation sign. A complete blood count test showed low neutrophil and lymphocyte count. ANA test was normal. Systemic Methyl Prednisolone 8 mg was prescribed 2 tabs twice a day and tapered off after the lesion resolved within 1 week. Supportive treatments include Benzydamine HCl and multivitamins. Discussion: Stress, anxiety, and depression were possible factors of OLP mediated by the Hypothalamic-pituitary-adrenal (HPA) axis system and the Sympathetic-adrenal-medullary (SAM) system. Specific mechanisms are mediated by Antigen-specific CD8+ (CTLs) that are activated with the help of CD4+ T-cells. Non-specific mechanism mediated by MMP-9 activation. They led to the apoptosis of keratinocytes. Systemic corticosteroids are an important treatment for oral lichen planus that do not responded to topical steroids. Conclusion: Oral Lichen Planus is a chronic inflammatory disease that affects the oral mucosa and can be predisposed by psychological stress. Corticosteroid is very effective to treat oral lichen planus, especially the erosive-ulcerative type. Keywords: Oral Lichen Planus, Psychological Stress, Ulcerative

Neuroendocrine stress hormones associated with short-term exposure to nitrogen dioxide and fine particulate matter in individuals with and without chronic obstructive pulmonary disease: A panel study in Beijing, China

Air pollution is a major trigger of chronic obstructive pulmonary disease (COPD). Dysregulation of the neuroendocrine hypothalamic-pituitary-adrenal (HPA) and sympathetic-adrenal medullary (SAM) axes is essential in progression of COPD. However, it is not clear whether air pollution exposure is associated with neuroendocrine responses in individuals with and without COPD. Based on a panel study of 51 stable COPD patients and 78 non-COPD participants with 384 clinical visits, we measured the morning serum levels of corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH), cortisol, norepinephrine, and epinephrine as indicators of stress hormones released from the HPA and SAM axes. Ambient nitrogen dioxide (NO2), fine particulate matter (PM2.5), and meteorological conditions were continuously monitored at the station from 2 weeks before the start of clinical visits. Linear mixed-effects models were used to estimate associations between differences in stress hormones following an average of 1–14-day exposures to NO2 and PM2.5. The average 1 day air pollutant levels prior to the clinical visits were 24.4 ± 14.0 ppb for NO2 and 55.6 ± 41.5 μg/m3 for PM2.5. We observed significant increases in CRH, ACTH, and norepinephrine, and decreases in cortisol and epinephrine with interquartile range increase in the average NO2 and PM2.5 concentrations in all participants. In the stratified analyses, we identified significant between-group difference in epinephrine following NO2 exposure in individuals with and without COPD. These results may suggest the susceptibility of COPD patients to the neuroendocrine responses associated with short-term air pollution exposure.

P134. Anterior Pituitary Volumes and Stress in Children and Adolescents With Chromosome 22q11.2 Deletion Syndrome

Children with 22q11.2DS have high rates of anxiety and 30% will develop a psychotic disorder by adulthood. The physiological effects of long-term stress and dysregulation of the hypothalamic-pituitary-adrenal cortical (HPA) and/or sympathetic adrenal medullary (SAM) systems may contribute to the etiopathology of mental illness in this population.

Personal ozone exposure and stress hormones in the hypothalamus-pituitary-adrenal and sympathetic-adrenal-medullary axes.

The effect of ozone exposure on neuroendocrine responses in humans has not been fully studied. We conducted a longitudinal panel study with four rounds of visits among 43 college students in Shanghai, China, from May to October 2016. For each visit, we monitored personal real-time ozone exposure for consecutive 3days (from 8:00 a.m. to 6:00p.m. each day), followed by blood sample collection. We measured serum levels of three hormones in the hypothalamus-pituitaryadrenal (HPA) axis, including corticotropin releasing hormone (CRH), adrenocorticotropic hormone (ACTH), and cortisol, and three catacholamines indicating sympathetic-adrenal-medullary (SAM) axis activation, including adrenaline, noradrenaline, and dopamine. We applied linear mixed-effect models to evaluate the associations between ozone exposure and these neurohormones and further compared models using personal and fixed-site ozone measurements. At lag 0-8h, personal ozone exposure ranged from 4.5ppb to 104.3ppb with an average of 21.0±14.7ppb, which was approximately half of the ambient ozone concentration. Per 10-ppb increase in personal ozone exposure (lag 0-8h) was associated with increases of 5.60% [95% confidence interval (CI): 2.30%, 9.01%] in CRH, 5.91% (95% CI: 0.55%, 11.56%) in cortisol, and 10.13% (95% CI: 2.75%, 18.05%) in noradrenaline, whereas associated with a 12.15% (95% CI: 1.23%, 21.87%) decrease in dopamine. Overall, models using personal ozone measurements yielded larger effect estimates and better model fits than models using fixed-site measurements. Short-term exposure to low levels of ozone may lead to activation of the HPA and SAM axes.

Abstract 11105: Real Time Racial Microaggression and Physiological Stress Responses Among Young and Middle Aged Black Adults

Introduction: Perceived racial discrimination has been associated with dysregulation of sympathetic-adrenal-medullary (SAM) and hypothalamic-pituitary-adrenal (HPA) axis, two major physiological stress response systems linked to cardiovascular disease outcomes. Most studies, to date, used cross-sectional data that captured retrospective measures of lifetime racial discrimination associated with current physiological stress responses. Relative to overt racial discrimination, a subtle form of racial discrimination, known as microaggression is more prevalent, yet most commonly measured retrospectively, and understudied. The purpose of this pilot study was to examine the relationship between microaggression measured in real-time and physiological stress responses. Methods: Twelve healthy Black adults (mean age=43.4 years) completed baseline surveys, and self-collected saliva 4x a day for 4 days to measure cortisol and alpha amylase (AA) as a proxy of HPA and SAM systems, respectively. Real-time microaggression was measured using ecological momentary assessments (EMA) sent to participants 5x a day for 7 days. Multilevel models were conducted to examine the relationship between microaggressions and the SAM and HPA axis activities. Results: In the bivariate analyses, the area under the curve with respect to ground (AUCg: total cortisol output throughout the day) was significantly associated with the same day microaggression (r=.40, p=.02). Microaggression was associated with cortisol awakening response (CAR) on the same day (r=.34, p=.04). In multilevel models, microaggression was associated with wake-up cortisol level on the same day (β=.22, p=.05). Microaggression was also associated with wake-up AA levels both the same day (β=.58, p<.01) and the next day (β=.40, p=.05). Conclusions: Microaggression was associated with same day and next day physiological stress responses. We determined that concurrent use of salivary biomarkers and EMA was feasible methods to examine the temporal relationship between microaggression and physiological stress responses. Future work will include the development of an intervention that buffers the physiologic stress response related to microaggression to improve cardiovascular health.

Stability and test-retest reliability of different hormonal stress markers upon exposure to psychosocial stress at a 4-month interval

The Trier Social Stress Test (TSST) has been shown to reliably induce physiological stress responses in the hypothalamus-pituitary-adrenal (HPA) and in the sympathetic-adrenal-medullary (SAM) axis in cross-sectional studies. However, it was also reported that repeated exposure to the TSST might be associated with habituation, mainly of the HPA axis responsivity. Thus, in all longitudinal stress studies involving repeated TSST administration, potential habituation of the HPA axis response complicates the interpretation of results. The goal of the present study was therefore to assess stability and test-retest reliability of a number of different endocrinological stress markers as well as subjective stress responses after two exposures to the TSST four months apart. We assessed salivary and plasma cortisol profiles, plasma ACTH and noradrenaline profiles, as well as subjective stress ratings in healthy volunteers before, during, and after the TSST at six time-points both at test-day 1 (TSST_1, n = 42) and test-day 2 (TSST_2, n = 34) 4-months later. Half of the participants received the TSST in the early, the other half in the late afternoon. Discontinuous growth models were applied to model three phases of the stress response (preTSST, reactivity, recovery) for each marker. Subsequently, the stability of these phases was analyzed. Stability and test-retest reliability of standard physiological stress markers such as Area-under-the-Curve (AUCG, AUCI), Absolute Peak Change, and Relative Peak Change (RPC) were analyzed as well. We did not observe strong test-retest effects in any of the endocrinological measures. In contrast, test-retest effects in subjective stress were characterized by a faster drop directly after the second TSST, whereas the initial increase before the test period was the same for both test-days. Regarding test-retest-reliability, AUCG was the most reliable measure across all endocrinological and subjective stress markers (range: r = .606 to .858), while AUCI and RPC (range: r = − .146 to .548) were least reliable. A 4-month interval is a sufficient time interval between two repeated TSST exposures to largely reinstate the physiological stress response, which was also true for the initial psychological stress response. Thus, the TSST is well applicable in longitudinal studies.

The Immune System Can Hear Noise.

As a stressor widely existing in daily life, noise can cause great alterations to the immune system and result in many physical and mental disorders, including noise-induced deafness, sleep disorders, cardiovascular diseases, endocrine diseases and other problems. The immune system plays a major role in maintaining homeostasis by recognizing and removing harmful substances in the body. Many studies have shown that noise may play vital roles in the occurrence and development of some immune diseases. In humans, both innate immunity and specific immunity can be influenced by noise, and different exposure durations and intensities of noise may exert various effects on the immune system. Short-term or low-intensity noise can enhance immune function, while long-term or high-intensity noise suppresses it. Noise can lead to the occurrence of noise-induced hearing loss (NIHL) through the production of autoantibodies such as anti-Hsp70 and anti-Hsp60 and exert adverse effects related to other immune-related diseases such as some autoimmune diseases and non-Hodgkin lymphoma. The neuroendocrine system, mainly including the hypothalamic-pituitary-adrenal (HPA) axis and the sympathetic-adrenal-medullary (SAM) system, is involved in the mechanisms of immune-related diseases induced by noise and gut microbiota dysfunction. In addition, noise exposure during pregnancy may be harmful to the immune system of the fetus. On the other hand, some studies have shown that music can improve immune function and alleviate the adverse effects caused by noise.

Dissociation of endocrine responses to the Trier Social Stress Test in Virtual Reality (VR-TSST) by the benzodiazepine alprazolam and the translocator protein 18 kDa (TSPO) ligand etifoxine

BackgroundActivity of the two major stress systems, the hypothalamic-pituitary-adrenal (HPA) and the sympathetic-adrenal-medullary (SAM) axis, has already been shown to be modulated by different compounds that bind to the central benzodiazepine receptor. Less is known about ligands that modulate the peripheral benzodiazepine receptor – meanwhile known as the translocator protein 18 kDa (TSPO) – which constitute promising candidates in the search of novel anxiolytics. To close this gap, the present study compared the effects of the benzodiazepine alprazolam and the TSPO ligand etifoxine on responses of the HPA and SAM axes to the Trier Social Stress Test, a standardized paradigm to induce acute psychosocial stress in humans, performed in Virtual Reality (VR-TSST). MethodsSixty healthy males, aged between 18 and 55 years, were randomly assigned to receive either a daily dose of 1.5 mg alprazolam, 150 mg etifoxine, or placebo over five days. On the last day of intake, they were exposed to the VR-TSST. We assessed changes of salivary cortisol, allopregnanolone, (nor-) epinephrine in serum, TSPO expression in platelets as well as heart rate (HR), skin conductance level (SCL) and self-reports in response to the stress task. Repeated measures ANOVAs were conducted to examine treatment effects on these stress response variables during the course of VR-TSST. ResultsThe response of salivary cortisol to the VR-TSST was significantly blunted in participants pre-treated with alprazolam but was not affected by etifoxine. While levels of allopregnanolone, epinephrine and norepinephrine increased in response to stress, TSPO expression decreased. None of those endocrine stress markers was affected by the active treatments, whereas TSPO expression increased after etifoxine administration over all study days. There were no effects of the two anxiolytics on HR, SCL or any self-report measurement. ConclusionThe current study confirmed the attenuating effects of benzodiazepines on stress-induced HPA axis activity but did not reveal a comparable effect of the TSPO ligand etifoxine. The long-term consequences of a pharmacologically blunted response of the HPA axis to an acute stressor should be further elucidated. Due to the missing effects of etifoxine on stress-related parameters in our sample of healthy subjects, it might be concluded that the therapeutic effects of this TSPO ligand are restricted to stronger or pathological stress responses, respectively.

EVALUATION OF ASSOCIATION OF ANTHROPOMETRIC INDICES WITH STRESS RESPONSE IN PCOS POPULATION

Background: Polycystic ovary syndrome (PCOS) is a complex endocrinopathy of women in their reproductive age with diversity in clinical manifestations. The phenotypic expressions and altered anthropometric indices are the key indicators of the abnormal transformations in metabolic, endocrine, and reproductive functionality of PCOS. Stress-induced activation of the Sympathetic-Adrenal-Medullary (SAM)-system and Hypothalamic-Pituitary-Adrenal (HPA)-axis results in series of neuroendocrine adaptations where over-activation of SAM/HPA response negatively affects the Hypothalamic-Pituitary-Gonadal (HPG) axis that highlight the possibility of the adverse impact of stress response system on reproductive and metabolic functions. Psychological distress and anxiety induced by the COVID-19 pandemic may aggravate the expressivity of PCOS and associated complexities. Objective: The present study aimed to find out some phenotypic features (hirsutism, acne, Acanthosis Nigricans (AN) and alopecia) in association with deviated anthropometric and derived indices, and stress biomarkers (Salivary α-amylase (SAA) and cortisol of SAM and HPA-axis respectively) among PCOS patients. Statistical analysis: SPSS (IBM, version 20) and Microsoft Office Excel 2010 were implied, and the quantitative variables were described as mean±SD (P < 0.01 and P < 0.05). Results: Significant alternations in the anthropometric indices were observed for PCOS patients that may lead to health risk. Alteration in body composition was strongly correlated with stress biomarkers in the case of both the experimental and control group. Central obesity was found to be a significant indicator of altered body composition in response to stress. Conclusion: Stress is a key modulator in the alternation of phenotypic manifestation as well as body composition of PCOS patients which could be the plausible reason for further deterioration of this multifaceted disorder due to the COVID-19 pandemic.

Abstract P301: Differences in Stress Related Behavior According to Age of Immigration: Insight From the Africans in America Study

Background: Adjusting to the stress of life in the United States is associated with unhealthy assimilation behaviors, such as cigarette smoking and alcohol consumption. Allostatic load score (ALS) is a measure of the accumulative effect of stress due to overactivation of the hypothalamic-pituitary-adrenal (HPA) and sympathetic adrenal medullary (SAM) axes. It is unknown if stress related behaviors vary according to whether immigration occurred as a child (<18y) or as an adult (≥18y). Objective: Our goal was to measure stress by ALS in 382 African-born blacks living in the Washington, DC metropolitan area (age 39±10y, range 20 to 65y) and compare social and behavioral factors in Africans who migrated to the United States as children versus as adults. Methods: ALS was calculated using 10 biomarkers from the 3 physiological systems affected by the HPA and SAM axes: cardiovascular (systolic BP, diastolic BP, pulse, cholesterol, HDL, homocysteine), metabolic (BMI, A1C, albumin) and inflammatory (hsCRP). One point was assigned if a variable was determined to be in the high-risk range and 0 if not. High-risk was defined by being in the highest quartile for the population distribution of each variable, except for albumin and HDL, which required the lowest quartile. Results: Of the 382 enrollees, 18% (68/382) came to the United States as children and 82% (314/382) were adults. Compared to adulthood immigrants, childhood immigrants were younger (31±9 vs. 41±10y, P <0.001) and had been in the United States longer (22±9 vs.11±10y, P <0.001). After adjusting for age, ALS was similar in the child and adult immigrants (2.6±0.02 vs.2.6±0.01, P =0.84). Alcohol intake was higher in immigrants who came as children than immigrants who came as adults (40% vs. 25%, P =0.02). Cigarette smoking, sedentary behavior and number of meals outside of the home all tended to be higher in the childhood immigrants ( P <0.2). In addition, childhood immigrants were more likely to self-identify as African-Americans than Africans (16% vs. 7%, P =0.05). Conclusion: Independent of whether Africans came to the United States as children or adults, degree of stress as measured by ALS is similar. However, Africans who arrived as children were more likely to develop unhealthy assimilation behaviors. Whether these behaviors are due to longer duration of stay in the United States or a generational difference remains to be determined.