Sympathetic-adrenal-medullary Axes Research Articles

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.

Unbiased multitissue transcriptomic analysis reveals complex neuroendocrine regulatory networks mediated by spinal cord injury-induced immunodeficiency

BackgroundSpinal cord injury (SCI), which causes loss of sensory and motor function in the body below the level of injury, is a devastating disease of the central nervous system. SCI leads to severe secondary immunosuppression, called SCI-induced immunodeficiency syndrome (SCI-IDS), which is characterized by increased susceptibility to infection and further exacerbates neurological dysfunction. Several studies have suggested that SCI-IDS is an independent risk factor for poor neurological prognosis. SCI-IDS predominantly occurs following injury above the T5 levels and eventually leads to systemic immune failure, possibly via the sympathetic–adrenal medullary axis and the hypothalamic‒pituitary‒adrenal (HPA) axis. However, the mechanism remains unclear.Methods and objectivesThe concentrations of adrenocorticotropic hormone and cortisol in plasma, as well as changes in sympathetic activity (blood pressure and catecholamine levels in plasma), were assessed in rats in the high-level (T3) spinal cord injury (T3-SCI) group and the low-level (T10) spinal cord injury (T10-SCI) group. Second, the differential regulation of the gene network between the sympathetic–adrenal medullary axis and the HPA axis was explored by histology and multitissue transcriptomics, and the neuroendocrine–immune network associated with SCI-IDS was further elucidated.ResultsThe spleen and thymus gland, which are secondary immune organs, were significantly atrophied in rats in the T3-SCI group, and the white pulp of the spleen was significantly atrophied. The level of cortisol, which is mediated by the adrenal glands, was markedly elevated, but norepinephrine levels were markedly decreased. There was no difference in adrenocorticotropic hormone expression between any of the groups. The transcriptome analysis results showed that the downregulated differentially expressed genes (DEGs) in the T3-SCI group were enriched in the GO term immunoregulation, indicating that splenic immune function was markedly impaired after high-level SCI. The upregulated DEGs in the hypothalamus (hub genes: Nod2, Serpine1, Cebpb, Nfkbil1, Ripk2, Zfp36, Traf6, Akap8, Gfer, Cxcl10, Tnfaip3, Icam1, Fcgr2b, Ager, Dusp10, and Mapkapk2) were significantly enriched in inflammatory pathways, and the downregulated genes (hub genes: Grm4, Nmu, P2ry12, rt1-bb1, Oprm1, Zfhx2, Gpr83, and Chrm2) were enriched in pathways related to inhibitory Gi-mediated G protein-coupled receptor (Gi-GPCR) neurons and neuropeptide changes. The upregulated genes in the adrenal glands (hub genes: Ciart, per2, per3, cry1, and cry2) were enriched in cortisol secretion and circadian rhythm changes, and the downregulated genes (hub genes: IL7r, rt1-bb, rt1-bb1, rt1-da, rt1-ba, cd74, cxcr3, vcam1, ccl5, bin1, and IL8) were significantly enriched in MHC-mediated immune responses.ConclusionsTo explore the possible mechanism underlying SCI-IDS, this study assessed the differential regulation of the gene network associated with neuroendocrine immunity after SCI. Progressive neuroinflammation spreads after injury, and neurotransmission through Gi-mediated G protein-coupled receptors in the HPA axis and neuropeptide production by the hypothalamus are inhibited. Disruption of the connection between the hypothalamus and the adrenal glands causes autonomous regulation of the adrenal glands, disturbance of circadian rhythm and finally hypercortisolemia, leading to general suppression of peripheral adaptive immunity. Neuraxial nerve inflammation caused by SCI persists indefinitely, blocking nerve repair; persistent system-wide immunosuppression in the periphery results in increased susceptibility to infection, leading to poor neurological prognosis.

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.

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.

The Brain-Skin Axis in Psoriasis-Psychological, Psychiatric, Hormonal, and Dermatological Aspects.

Psoriasis is a chronic inflammatory skin disease with systemic manifestation, in which psychological factors play an important role. The etiology of psoriasis is complex and multifactorial, including genetic background and environmental factors such as emotional or physical stress. Psychological stress may also play a role in exacerbation of psoriasis, by dysregulation of the hypothalamic–pituitary–adrenal (HPA) axis, sympathetic–adrenal–medullary axis, peripheral nervous system, and immune system. Skin cells also express various neuropeptides and hormones in response to stress, including the fully functional analog of the HPA axis. The deterioration of psoriatic lesions is accompanied by increased production of inflammatory mediators, which could contribute to the imbalance of neurotransmitters and the development of symptoms of depression and anxiety. Therefore, deregulation of the crosstalk between endocrine, paracrine, and autocrine stress signaling pathways contributes to clinical manifestations of psoriasis, which requires multidisciplinary approaches.

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.

Effects of Withania somnifera (Ashwagandha) on Stress and the Stress- Related Neuropsychiatric Disorders Anxiety, Depression, and Insomnia.

Background Withania somnifera (WS), also known as Ashwagandha, is commonly used in Ayurveda and other traditional medicine systems. WS has seen an increase in worldwide usage due to its reputation as an adaptogen. This popularity has elicited increased scientific study of its biological effects, including a potential application for neuropsychiatric and neurodegenerative disorders.Objective This review aims to provide a comprehensive summary of preclinical and clinical studies examining the neuropsychiatric effects of WS, specifically its application in stress, anxiety, depression, and insomnia.Methods Reports of human trials and animal studies of WS were collected primarily from the PubMed, Scopus, and Google Scholar databases.Results WS root and leaf extracts exhibited noteworthy anti-stress and anti-anxiety activity in animal and human studies. WS also improved symptoms of depression and insomnia, though fewer studies investigated these applications. WS may alleviate these conditions predominantly through modulation of the hypothalamic-pituitary-adrenal and sympathetic-adrenal medullary axes, as well as through GABAergic and serotonergic pathways. While some studies link specific withanolide components to its neuropsychiatric benefits, there is evidence for the presence of additional yet unidentified active compounds in WS.Conclusion While benefits were seen in the reviewed studies, significant variability in the WS extracts examined prevents a consensus on the optimum WS preparation or dosage for treating neuropsychiatric conditions. WS generally appears safe for human use; however, it will be important to investigate potential herb-drug interactions involving WS if used alongside pharmaceutical interventions. Further elucidation of active compounds of WS is also needed.

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.

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.

Single oral administration of flavan 3-ols induces stress responses monitored with stress hormone elevations in the plasma and paraventricular nucleus

We previously confirmed that postprandial alterations in the circulation and metabolism after a single oral dose of flavan 3-ols (mixture of catechin and catechin oligomers) were involved in an increase in sympathetic nervous activity. However, it is well known that, in response to various stresses, activation of the hypothalamic-pituitary-adrenal (HPA) axis occurs together with sympathetic nerve activity, which is associated with activation of the sympathetic-adrenal-medullary (SAM) axis. In this study, we examined whether the HPA axis was activated after a single dose of flavan 3-ols. We administered an oral dose of 10 or 50 mg/kg flavan 3-ols to male ICR mice, removed the brains, and fixed them in paraformaldehyde-phosphate buffer. Other animals that were treated similarly were decapitated, and blood was collected. In the paraventricular nucleus (PVN), c-fos mRNA expression increased significantly at 15 min after administration of either 10 or 50 mg/kg flavan 3-ols. Corticotropin-releasing hormone (CRH) mRNA expression levels significantly increased at 240 min after administration of 10 mg/kg flavan 3-ols, and at 60 min after administration of 50 mg/kg flavan 3-ols. Plasma corticosterone levels were also significantly increased at 240 min after ingestion of 50 mg/kg flavan 3-ols. In this experiment, we confirmed that the ingestion of flavan 3-ols acted as a stressor in mammals with activation both the SAM and HPA axes.

Antistress effects of Kampo medicine "Yokukansan" via regulation of orexin secretion.

ObjectiveVarious stressors induce stress responses through the hypothalamic–pituitary–adrenal and the sympathetic–adrenal–medullary axes, which are regulated, in part, by orexin. For example, secretion of orexin in the hypothalamus is increased in rats exposed to the stress of social isolation for 1 week. In this study, the antistress effects of Kampo medicine Yokukansan (YKS) via the regulation of orexin secretion were investigated using a rat model.Methods and resultsThe administration of 300 mg/kg per day of YKS to rats for 1 week significantly decreased the plasma orexin levels compared with non-treated rats, whereas the administration of 1,000 mg/kg of YKS had no effect on orexin levels. Therefore, 300 mg/kg of YKS was an effective dose for controlling orexin secretion. Subsequently, rats were divided into group-housed control (Con), individually housed stress (Stress), and individually housed YKS (300 mg/kg)-treated stress (Stress + YKS) groups. After 1 week, a resident–intruder aggression test was performed, and the plasma levels of orexin and corticosterone were measured. In the Stress group, aggressive behavior and the levels of corticosterone and orexin significantly increased compared with the Con group; however, these effects were inhibited in the Stress + YKS group. Further, an orexin receptor antagonist (TCS 1102; 10 mg/kg) was intraperitoneally administered to rats exposed to isolation stress to determine whether orexin was involved in stress responses. Under these conditions, aggressive behavior and the level of corticosterone significantly decreased compared with the Stress group.ConclusionThese results suggest that orexin is involved in the control of stress response and that YKS exerts an antistress effect via the regulation of orexin secretion.

Transient changes in inflammatory and oxidative stress markers with total sleep deprivation

Sleep deprivation (SD) is known to modulate inflammatory and oxidative stress markers. How these markers change over the SD period have seldom been studied in healthy young adults. Seventeen healthy young adults with a mean age of 19.8 ± 1.0 years underwent an experimental protocol consisting of 36 h of total SD. We tested whether the stress response was towards adaptation or a worsening of the response. We analysed blood for gene expression levels of interleukins (IL-1β, IL-6, IL-33), tumour necrosis factor-α (TNF-α), glutathione (GSH), heat-shock protein 70 (HSP70), and a member of the signal transducers and activators of transcription (STAT3) family with quantitative real-time polymerase chain reaction (qRT-PCR). We also measured plasma levels of cortisol and malondialdehyde (MDA) with a spectrophotometer. All measurements were made at baseline and at the 24th and 36th hour of the study. IL-1β, IL-6, and GSH gene expression levels were up-regulated at the 24th hour and down-regulated at the 36th hour (p < 0.05 for all). IL-33 gene expression levels showed no change at the 24th hour and down-regulation at the 36th hour. TNF-α gene expression levels were down-regulated at the 24th hour and up-regulated at the 36th hour. Cortisol levels showed a gradual increase at all the measurement points (p < 0.05 for all). HSP70, MDA, and STAT3 had no significant changes. The present study demonstrated that the hyperactivation of the hypothalamic–pituitary–adrenal (HPA) and sympathetic-adrenal-medullary (SAM) axes shown by the up-regulation of genes seen after a sleepless night is a normal response to acute stress, and by increasing the time spent sleepless, the HPA and SAM axes may return to their normal functioning levels.

Norepinephrine Regulates Keratinocyte Proliferation to Promote the Growth of Hair Follicles

Psychological factors and stress can cause hair loss. The sympathetic-adrenal-medullary (SAM) axis has been reported to regulate the growth of hair follicles (HF). The sympathetic nerve is a component of the SAM axis, but it has not been sufficiently or convincingly linked to hair growth. In this study, we demonstrate that chemical sympathectomy via administration of the neurotoxin 6-hydroxydopamine (6-OHDA) to mice inhibited HF growth, but treatment with the β-adrenoceptor antagonist propranolol (PR) had no effect. HF length and skin thickness were greater in PR-treated and control mice than in 6-OHDA-treated mice, as evidenced by hematoxylin and eosin staining. Furthermore, we found that the reduced HF growth in sympathectomized animals was accompanied by a decreased keratinocyte proliferation. Moreover, the neurotransmitter norepinephrine (NE) was found to efficiently promote HF growth in an organotypic skin culture model. Together, these findings suggest that sympathetic nerves regulate keratinocyte behaviors to promote hair growth, providing novel insights into stress-related, chemotherapy-, and radiotherapy-induced alopecia.

Salivary Alpha-Amylase Reactivity in Breast Cancer Survivors.

The two main components of the stress system are the hypothalamic-pituitary-adrenal (HPA) and sympathetic-adrenal-medullary (SAM) axes. While cortisol has been commonly used as a biomarker of HPA functioning, much less attention has been paid to the role of the SAM in this context. Studies have shown that long-term breast cancer survivors display abnormal reactive cortisol patterns, suggesting a dysregulation of their HPA axis. To fully understand the integrity of the stress response in this population, this paper explored the diurnal and acute alpha-amylase profiles of 22 breast cancer survivors and 26 women with no history of cancer. Results revealed that breast cancer survivors displayed identical but elevated patterns of alpha-amylase concentrations in both diurnal and acute profiles relative to that of healthy women, F (1, 39) = 17.95, p < 0.001 and F (1, 37) = 7.29, p = 0.010, respectively. The average area under the curve for the diurnal and reactive profiles was 631.54 ± 66.94 SEM and 1238.78 ± 111.84 SEM, respectively. This is in sharp contrast to their cortisol results, which showed normal diurnal and blunted acute patterns. The complexity of the stress system necessitates further investigation to understand the synergistic relationship of the HPA and SAM axes.

Psoriasis and Psycho-Dermatology

IntroductionPsoriasis is a common, long-term skin condition associated with high levels of psychological distress and considerable life impact. The impact of psoriasis, beyond the skin, is often not recognised and under-treated.MethodsThis paper explores the relationship between psychological distress and psoriasis including reference to the ‘brain–skin access’. The life impact of psoriasis is discussed and pharmacological interventions which affect distress associated with psoriasis and psychological interventions are reviewed. Evidence from peer-reviewed journals and controlled trials inform the text.ResultsPsoriasis has a profound impact on mental health and well-being which is under-recognised by clinicians. The sympathetic adrenal medullary axis and hypothalamic pituitary adrenal axis are likely to be involved in the onset of psoriasis and there may also be an effect from inflammation in the skin on the central release of corticotrophin-releasing hormone. Psoriasis can be stigmatising and may affect all aspects of life including relationships, employment, social life and leisure activities. There is some evidence for psychological interventions being effective in the management of distress associated with psoriasis and psoriasis itself. Studies, however, have used disparate outcomes and methods and largely involve low numbers of patients. There is very limited access to psychological support for the patients with psoriasis despite evidence of high levels of psychological distress and considerable life impact.ConclusionsPsoriasis is a long-term skin condition associated with high levels of distress and considerable life impact, both of which are under-recognised. Routine screening for distress with access to effective treatment is required. There is a need for high-quality studies to assess the effect of psychological intervention in patients with psoriasis both to inform guidance and facilitate the provision of effective psychological support services.

Combined food intake and exercise unmask different hormonal responses in lean and obese children

Our purpose was to investigate the effect of obesity in prepubertal children on the hormonal response to exercise performed under different conditions of nutrient availability. Prepubertal obese (age, 10.3 ± 1.8 years; %body fat, 36.1 ± 6.1; n = 9) and lean (age, 9.2 ± 1.6 years; %body fat, 22.2 ± 4.1; n = 7) children completed 2 experimental sessions in which they performed a 30 min of cycling exercise at 50% of their maximal aerobic power either 1 h (T1h) or 3 h (T3h) after a standardized breakfast. Plasma insulin-like growth factor 1 (IGF-1), IGF binding protein 1 (IGFBP-1), and IGFBP-3 levels were assessed at baseline and after exercise. Urine was collected during the sessions, and catecholamine and glucocorticoid excretions were analyzed. A significant time effect was observed for IGFBP-1; postexercise levels decreased in lean and obese children (p ≤ 0.001). IGF-1 and IGFBP-3 were not affected by obesity or food intake combined with exercise. In lean children, urinary excretion rates of epinephrine, norepinephrine, cortisol, and cortisone were significantly higher during the sessions than during the overnight resting period; in obese children, only epinephrine in T1h was significantly increased (p ≤ 0.05 for all). Our study indicates that the activity of the hypothalamic-pituitary-adrenal axis and sympathetic adrenal medullary axis was similar in lean and obese children, based on measurement under resting conditions, but response to exercise performed in postprandial conditions was altered in obese children for both axes. In addition, exercise in the postprandial state elicited a decrease in IGFBP-1 plasma levels, whereas IGF-1 and IGFBP-3 levels were not significantly altered.

Salivary cortisol and α-amylase levels following admission to paediatric intensive care

Background The hypothalamus-pituitary-adrenal (HPA) and sympathetic-adrenal-medullary (SAM) axes play an important role in the stress responses of children with critical illness admitted to a paediatric intensive care unit (PICU). While lower levels of plasma cortisol during admission for meningococcal disease have been associated with higher mortality, it is not known whether critical illness affects the subsequent regulation of these stress response-mediating mechanisms, and whether any dysregulation is related to psychological sequelae. Aims The present investigation aims to assess whether HPA and SAM axis function, as measured by salivary cortisol and α-amylase (sAA)—two non-invasive markers of the activation of the HPA and SAM axis, respectively—is altered 3 to 6 months following critical illness and PICU admission. Methods The study is part of a prospective study of neuropsychological function in children following admission to PICU. Salivary cortisol and sAA levels of children aged 5 to 16 admitted to PICUs were documented 3–6 months following discharge, and compared as a whole group and as disorder subgroups (ie, meningoencephalitis, sepsis, and non-septic illness) with those of age and gender matched healthy controls. Salivary samples were collected at time of awaking, 30 min and 12 h after awaking, on two consecutive weekdays. Results Recruitment of participants is currently ongoing. Preliminary data from 19 children (10 males, 9 females) admitted to PICU (mean age: 10.53 years; SD 3.69) has been analysed and compared with data from 14 healthy controls (10 males, 4 females; mean age 11.93, SD 2.84). No differences between the whole PICU group and healthy controls were found on awaking or 30 min cortisol levels nor on any of the sAA measures, but there was a trend for lower evening cortisol in the PICU participants (p=.058). The comparison between PICU subgroups and healthy controls showed statistically significant lower evening cortisol levels in the non-septic illness subgroup (n=7) only (p=0.007). Conclusion Our preliminary findings suggest anomalies in cortisol regulation following admission to PICU. These findings need confirmation in a larger sample and their relevance for neurocognitive and emotional function require clarification.

Stress Hormone Responses to an Ultraendurance Race in the Cold

Physical stress (exercise and/or environmental) activates the sympathetic-adrenal-medullary (SAM) and hypothalamic-pituitary-adrenocortical (HPA) axes. The combination of ultraendurance exercise in the cold presents a unique summated stress to the body. The purpose of this study was to assess the stress hormone response in runners, cyclists, and skiers participating in a 161-km ultraendurance race on a snow-packed course in the Alaskan wilderness. Forty-four athletes (20 runners, 17 cyclists, 7 skiers) competed on the same course of snow-machine trails and ice roads with each athlete carrying 7 kg of mandatory equipment. Pre-race weight and blood samples were collected 2 days prior to the race start. Post-race measurements were made within 15 minutes of race finish. Hematocrit was measured, and blood samples were analyzed for levels of norepinephrine, epinephrine, adrenocorticotropic hormone, and cortisol. Runners lost significant weight (-1.74 kg +/- 1.29) pre-race to post-race. Hematocrit was maintained, and plasma volume increased minimally. Norepinephrine increased significantly pre-race (279.9 pg/mL +/- 356.9) to post-race (691.7 pg/mL +/- 422.6) with no difference among divisions. Epinephrine did not change significantly during the race. Adrenocorticotropic hormone (2.40 pg/mL +/- 2.40 to 19.04 pg/mL +/- 45.38) increased significantly with no difference among divisions. Cortisol increased significantly pre-race (12.03 microg/dL +/- 5.66) to post-race (26.69 microg/dL +/- 5.77), and post-race cortisol was significantly higher in runners vs skiers. These data suggest activation of both the SAM and HPA axes from an ultraendurance race in the cold and reveal the degree of stress hormone responses to this exhausting bout of exercise.