Short intense psychological stress induced by skydiving does not impair intestinal barrier function

Background and aim Psychological stress has been shown to increase intestinal permeability and is associated with the development of gastrointestinal disorders. This study aimed to investigate skydiving as an alternative model to analyse the effect of acute psychological stress on intestinal barrier function. Materials and methods Twenty healthy subjects participated in a tandem skydive followed by a negative control visit, of which 19 (9 females and 10 males, 25.9 ± 3.7 years) were included in the study. Intestinal permeability was assessed by a multi-sugar urinary recovery test. Sucrose recovery and lactulose/rhamnose ratio in 0-5h urine indicated gastroduodenal and small intestinal permeability, respectively, and sucralose/erythritol ratio in 5-24h urine indicated colonic permeability. Blood samples were taken to assess markers associated with barrier function. This study has been registered at ClinicalTrials.gov (NCT03644979) on August 23, 2018. Results Skydiving resulted in a significant increase in salivary cortisol levels directly after skydiving compared to the control visit. Cortisol levels were still increased two hours after landing, while cortisol levels before skydiving were not significantly different from the baseline at the control visit. Skydiving did not induce a significant increase in gastroduodenal, small intestinal or colonic permeability. There was also no significant increase in plasma intestinal and liver fatty acid-binding proteins, suggesting no damage to the enterocytes. Discussion These results show that the acute intense psychological stress induced by skydiving does not affect intestinal permeability in healthy subjects. Future models aiming to investigate the effect of stress on human intestinal barrier function should consider a more sustained exposure to the psychological stressor.

White matter in prolonged glucocorticoid response to psychological stress in schizophrenia

Stress is implicated in psychosis etiology and exacerbation, but pathogenesis toward brain network alterations in schizophrenia remain unclear. White matter connects limbic and prefrontal regions responsible for stress response regulation, and white matter tissues are also vulnerable to glucocorticoid aberrancies. Using a novel psychological stressor task, we studied cortisol stress responses over time and white matter microstructural deficits in schizophrenia spectrum disorder (SSD). Cortisol was measured at baseline, 0-, 20-, and 40-min after distress induction by a psychological stressor task in 121 SSD patients and 117 healthy controls (HC). White matter microstructural integrity was measured by 64-direction diffusion tensor imaging. Fractional anisotropy (FA) in white matter tracts were related to cortisol responses and then compared to general patterns of white matter tract deficits in SSD identified by mega-analysis. Differences between 40-min post-stress and baseline, but not acute reactivity post-stress, was significantly elevated in SSD vs HC, time × diagnosis interaction F2.3,499.9 = 4.1, p = 0.013. All SSD white matter tracts were negatively associated with prolonged cortisol reactivity but all tracts were positively associated with prolonged cortisol reactivity in HC. Individual tracts most strongly associated with prolonged cortisol reactivity were also most impacted in schizophrenia in general as established by the largest schizophrenia white matter study (r = −0.56, p = 0.006). Challenged with psychological stress, SSD and HC mount similar cortisol responses, and impairments arise in the resolution timeframe. Prolonged cortisol elevations are associated with the white matter deficits in SSD, in a pattern previously associated with schizophrenia in general.

029 Median preoptic dual control over sleep regulation

Introduction Previous studies suggest that the median preoptic nucleus (MnPO) plays an important role in regulating the wake-sleep cycle and in particular homeostatic sleep drive. However, the precise cellular phenotypes, targets and central mechanisms by which the MnPO neurons regulate the wake-sleep cycle remain unknown. Both glutamatergic (Vglut2+) and GABAergic (Vgat+) MnPO neurons innervate brain regions implicated in sleep promotion and maintenance, suggesting that both cell types may participate on sleep control. Methods In this study, we used two genetically-targeted approaches associated with electroencephalographic (EEG) and electromyographic (EMG) recordings in Vgat-IRES-cre and Vglut2-IRES-cre mice to investigate the role of the MnPOVgat and MnPOVglut2 neurons in modulating wake-sleep behavior. Results First, using a chemogenetic approach, we found that activation of MnPOVgat neurons reduced the latency for the first NREM sleep episode, produced an increase in NREM sleep and reduced wakefulness. Then, to test the role of MnPOVgat and MnPOVglut2 neurons in regulating sleep homeostasis, we recorded EEG and EMG responses in mice that had the Vgat+ or Vglut2+ neurons deleted from the MnPO. After deletion of MnPOVgat neurons, mice showed a reduction of NREM sleep and an increase in wakefulness during the light phase. Deletion of MnPOVgat neurons also reduced sleep recovery after 4 hours of sleep deprivation (SD). On the other hand, deletion of the MnPOVglut2 neurons did not change the wake-sleep cycle during the 24h baseline condition, but prevented the sleep recovery immediately after SD. To understand the underlying mechanism in preventing sleep recovery in both MnPOVglut2- and MnPOVgat-deleted mice groups, we exposed these animals to a psychological stress protocol. In response to a psychological stressor, mice with deletion of glutamatergic, but not GABAergic MnPO neurons, had an exacerbation of the stress-induced insomnia. Conclusion Our results suggest that both neuron populations differentially participate in wake-sleep control, with MnPOVgat neurons being critically involved in sleep homeostasis, and MnPOVglut2 neurons promoting sleep during allostatic (stressful) challenges. Support (if any) NIH Grants NS085477, NS072337, HL095491 and Sleep Research Society Foundation (Award 026-JP-20).

THE DIFFERENCES IN RESPONSE TO ACUTE STRESS OF INDIVIDUALS WITH HIGHER AND LOWER NEUROTICISM

"Although some studies analyze neuroticism's role in individuals' response to acute stress, the results are controversial. There is a lack of studies examining the response to stressors of individuals with higher and lower neuroticism in all phases (during the period of anticipation of the stressor, at the time of exposure to the stressor, and during the recovery period after exposure to a stressor), measuring different physiological parameters and evaluating emotional response to a stressor at the same time. This study aimed to assess individuals with higher and lower neuroticism physiological and emotional responses to acute stress. 168 students participated in a study (23 males and 145 females). Their response to 4 different stressors (1 physical and 3 psychological (with standard instruction, the pressure to compete and critique) was evaluated, measuring the changes in their skin conductance, skin temperature, heart rate, respiratory rate while waiting for the stressor (anticipation phase), during the stressor and in the stress recovery phase. The changes in students ‘emotional responses were also measured using the C.R. Carlson et al. (1989) Emotional Assessment Scale (EAS). Students’ neuroticism was assessed using the NEO Five-Factor Inventory's neuroticism subscale (NEO-FFI, Costa, McCrae, 1992). The study results showed that students having higher and lower neuroticism differed when reacting to a physiological stressor. Students' responses to a psychological stressor differed only in the condition when they were criticized."

Time-lag of urinary and salivary cortisol response after a psychological stressor in bonobos (Pan paniscus)

Cortisol is often measured as a marker for stress. Therefore, a profound validation of the time-lag between the stressor and the increase and peak in cortisol levels is needed. No study measured both the urinary and salivary cortisol time-lag after a psychological stressor. In this study, we used a frequent sampling study design to (1) describe the urinary and salivary cortisol pattern during a control day; and (2) characterize the induced excretion pattern of urinary and salivary cortisol after a psychological stressor in six zoo-housed bonobos. Liquid chromatography-tandem mass spectrometry was used to analyze 71 urine and 162 saliva samples collected on a control and a test day. We found that the time-lag between the stressor and the maximal cortisol concentration was similar in urine and saliva (160 min after the stressor). However, salivary cortisol after the stressor did show a faster and steeper increase than urinary cortisol. We also show inter-individual variation in the baseline and stress levels of cortisol, which should be considered in future cortisol studies. Our research highlights the importance of validation studies to confirm relevant sampling windows for cortisol sampling in order to obtain biologically meaningful results.

The ‘Jekyll and Hyde’ of Gluconeogenesis: Early Life Adversity, Later Life Stress, and Metabolic Disturbances

The physiological response to a psychological stressor broadly impacts energy metabolism. Inversely, changes in energy availability affect the physiological response to the stressor in terms of hypothalamus, pituitary adrenal axis (HPA), and sympathetic nervous system activation. Glucocorticoids, the endpoint of the HPA axis, are critical checkpoints in endocrine control of energy homeostasis and have been linked to metabolic diseases including obesity, insulin resistance, and type 2 diabetes. Glucocorticoids, through the glucocorticoid receptor, activate transcription of genes associated with glucose and lipid regulatory pathways and thereby control both physiological and pathophysiological systemic energy homeostasis. Here, we summarize the current knowledge of glucocorticoid functions in energy metabolism and systemic metabolic dysfunction, particularly focusing on glucose and lipid metabolism. There are elements in the external environment that induce lifelong changes in the HPA axis stress response and glucocorticoid levels, and the most prominent are early life adversity, or exposure to traumatic stress. We hypothesise that when the HPA axis is so disturbed after early life adversity, it will fundamentally alter hepatic gluconeogenesis, inducing hyperglycaemia, and hence crystalise the significant lifelong risk of developing either the metabolic syndrome, or type 2 diabetes. This gives a “Jekyll and Hyde” role to gluconeogenesis, providing the necessary energy in situations of acute stress, but driving towards pathophysiological consequences when the HPA axis has been altered.

The ‘Jekyll and Hyde’ of Gluconeogenesis: Early-Life Adversity, Later Life Stress, and Metabolic Disturbances

The physiological response to a psychological stressor broadly impacts energy metabolism. Inversely, changes in energy availability affect the physiological response to the stressor in terms of hypothalamus, pituitary adrenal gland axis and sympathetic nervous system activation upon exposure to a stressor. Glucocorticoids, the endpoint of the HPA axis, are critical checkpoints in endocrine control of energy homeostasis. Glucocorticoid actions have been linked to many severe metabolic diseases including obesity, insulin resistance and type 2 diabetes. Glucocorticoids, through the glucocorticoid receptor, activate transcription of many genes associated with glucose and lipid regulatory pathways and thereby intricately control both physiological and pathophysiological systemic energy homeostasis. Here, we summarize the current knowledge of glucocorticoid functions in energy metabolism and systemic metabolic dysfunction, particularly focusing on glucose and lipid metabolism. There are many elements in the external environment that induce lifelong changes in the HPA axis stress response and glucocorticoid levels, the most prominent are early-life adversity, or exposure to traumatic stress. We hypothesise that when the HPA axis is so disturbed after early-life adversity, it will fundamentally alter hepatic gluconeogenesis, inducing hyperglycaemia, and hence crystalise the significant lifelong risk of developing either the metabolic syndrome, or type 2 diabetes. This gives a “Jekyll and Hyde” role to gluconeogenesis, providing the necessary energy in situations of acute stress, but driving towards pathophysiological consequences when the HPA axis has been altered.

Nerve Injury Alters Restraint-induced Activation of the Basolateral Amygdala in Male Rats

The amygdala is critical for the production of appropriate responses towards emotional or stressful stimuli. It has a characteristic neuronal activation pattern to acute stressors. Chronic pain and acute stress have each been shown to independently modulate the activity of the amygdala. Few studies have investigated the effect of pain or injury, on amygdala activation to acute stress. This study investigated the effects of a neuropathic injury on the activation response of the amygdala to an acute restraint stress. Chronic constriction injury of the right sciatic nerve (CCI) was used to create neuropathic injury and a single brief 15-minute acute restraint was used as an emotional/psychological stressor. All rats received cholera toxin B (CTB) retrograde tracer injections into the medial prefrontal cortex (mPFC) to assess if the amygdala to mPFC pathway was specifically regulated by the combination of neuropathic injury and acute stress. To assess differential patterns of activity in amygdala subregions, cFos expression was used as a marker for “acute”, restraint triggered neuronal activation, and FosB/DFosB expression was used to reveal prolonged neuronal activation / sensitisation triggered by CCI. Restraint resulted in a characteristic increase in cFos expression in the medial amygdala, which was not altered by CCI. Rats with a CCI showed increased cFos expression in the basolateral amygdala (BLA), in response to an acute restraint stress, but not in neurons projecting to the prefrontal cortex. Further, CCI rats showed an increase in FosB/ΔFosB expression which was exclusive to the BLA. This increase likely reflects sensitisation of the BLA as a consequence of nerve injury which may contribute to heightened sensitivity of BLA neurons to acute emotional/ psychological stressors.

Effect of COVID-19 stressors on healthcare workers’ performance and attitude at Suez Canal university hospitals

Background Coronavirus disease 2019 is an emerging respiratory disease caused by a novel coronavirus effect on 10-20% of total healthcare workers and was first detected in December 2019 in Wuhan, China. This study was designed to assess effect of COVID-19 stressors on healthcare workers’ performance and attitude. A descriptive cross sectional research design was used. A convenient sample (all available healthcare workers) physicians “112,”, nurses “183,” pharmacists “31,” and laboratory technicians “38” was participated to conduct aim of the study. Utilize the study with two tools; online self-administrated questionnaire to assess level of knowledge, attitude, and infection control measures regarding coronavirus disease 2019 and COVID-19 stress scales to assess the varied stressors among healthcare workers. Results More than three quarter of the studied participants had satisfactory level of knowledge and infection control measures. Approximately all of the studied participants had positive attitude regarding COVID-19. A total of 57.4% of the studied medical participants had moderate COVID-19 psychological stress levels, while 49.1% of the studied paramedical participants had moderate COVID-19 psychological stress levels. But less than one quarter had severe COVID-19 psychological stress levels. There is a significant correlation between COVID-19 psychological stressor levels and satisfactory level of knowledge among medical participants. Conclusion/implications for practice Most of healthcare workers had satisfactory level of knowledge, infection control measures, and positive attitude regarding COVID-19. Most of them had moderate COVID-19 psychological stress levels.