11Beta-hydroxysteroid dehydrogenase type 1 activity in medial vestibular nucleus and cerebellum after unilateral vestibular deafferentation in the rat

In the early stages of vestibular compensation (VC) (the behavioural recovery that follows unilateral vestibular deafferentation), neurons in the medial vestibular nucleus (MVN) on the lesioned side develop a sustained up-regulation of their intrinsic excitability. This plasticity is dependent on the activation of glucocorticoid receptors, which presumably occurs during the acute stress response that accompanies the vestibular deafferentation symptoms. Recent studies have established that the access of glucocorticoids to their intracellular receptors in brain is potently modulated by 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1), which catalyses the generation of active glucocorticoids from their inert 11-keto forms. In this study, we investigated the presence of 11beta-HSD1 bioactivity, and possible changes in activity in the early stage after vestibular deafferentation, in the cerebellar nodulus and uvula, the flocculus/paraflocculus (F/PF) complex and the MVN of the rat. 11beta-HSD1 activity was found in each of these brain areas, with especially high levels of activity in the F/PF complex. No differences were found in the level of 11beta-HSD1 activity in these brain areas between control rats, sham-operated rats and rats that underwent VC for 4 h after unilateral vestibular deafferentation. These findings demonstrate 11beta-HSD1 bioactivity in the MVN and vestibulocerebellum, but exclude the possibility that changes in 11beta-HSD1 activity occur in the early period after deafferentation, over the time when changes in MVN neuronal properties take place.     

Psychosocial stress impairs working memory at high loads: an association with cortisol levels and memory retrieval

Stress and cortisol are known to impair memory retrieval of well-consolidated declarative material. The effects of cortisol on memory retrieval may in particular be due to glucocorticoid (GC) receptors in the hippocampus and prefrontal cortex (PFC). Therefore, effects of stress and cortisol should be observable on both hippocampal-dependent declarative memory retrieval and PFC-dependent working memory (WM). In the present study, it was tested whether psychosocial stress would impair both WM and memory retrieval in 20 young healthy men. In addition, the association between cortisol levels and cognitive performance was assessed. It was found that stress impaired WM at high loads, but not at low loads in a Sternberg paradigm. High cortisol levels at the time of testing were associated with slow WM performance at high loads, and with impaired recall of moderately emotional, but not of highly emotional paragraphs. Furthermore, performance at high WM loads was associated with memory retrieval. These data extend previous results of pharmacological studies in finding WM impairments after acute stress at high workloads and cortisol-related retrieval impairments.     

Psychosocial stress and HPA functioning: no evidence for a reduced resilience in healthy elderly men

In order to investigate if HPA functioning is altered with age, the present study was conducted. Fifteen healthy elderly men (60-76 years; mean age 66.5 +/- 1.48 yrs.) and 12 younger adults (20-29 years; mean age 25.6 +/- 0.77 yrs.) collected salivary free cortisol profiles after awakening for basal HPA activity. Then, all subjects were exposed to the "Trier Social Stress Test" (TSST). This psychosocial stress protocol consists of a free speech and a mental arithmetic task of 13 minutes duration performed in front of an audience. Beside the assessment of endocrine and cardiovascular responses to the stressful task ratings of depression, mood and perceived stressfulness were obtained. Results show that younger and elderly men had similar morning cortisol profiles after awakening with both groups showing the expected rise after awakening (P=0.004). The TSST induced significant increases in ACTH, total plasma cortisol, saliva free cortisol, and heart rates (all P<0.0001). Regardless of age, both age groups showed comparable endocrine response patterns when confronted with the stressor. However, cardiovascular responses were significantly higher in younger men compared to elderly men (P=0.03). Catecholamine data revealed significant norepinephrine and epinephrine increases due to the stressor (both P<0.0001) with a trend toward elevated norepinephrine levels in elderly men (P=0.058). In sum, the investigated basal and response parameters of HPA functioning neither support the idea of a reduced resilience in healthy aged humans nor do they appear to strengthen assumptions derived from the so called "glucocorticoid cascade hypothesis".     

Salivary cortisol concentrations, stress and quality of life in women with endometriosis and chronic pelvic pain

The objective of this study was to evaluate the perceived stress index, quality of life, and hypothalamus-pituitary-adrenal axis activity in women with endometriosis and chronic pelvic pain. For the study, 93 women with endometriosis and 82 healthy women volunteered. The visual analogue scale (VAS) (0=no pain; 10=severe pain) was used to determine pain intensity; the perceived stress questionnaire (PSQ) defined stress index, and the health-related quality-of-life (HRQOL)-SF-36 questionnaire was used to evaluate quality of life. Salivary cortisol was measured at 0800, 1600, and 2000 h and the awakening cortisol response was assessed to evaluate the hypothalamus-pituitary-adrenal axis activity. The results show that women with endometriosis and chronic pelvic pain of moderate intensity (4.1+/-0.58, mean+/-SEM) have higher levels of perceived stress (0.55+/-0.01 versus 0.42+/-0.01, p<0.05), a poorer quality of life expressed as lower scores for all items of the inventory and hypocortisolism. Lower levels of salivary cortisol were observed in all three samples collected, as well as in the awakening cortisol response, for women with endometriosis (0.19+/-0.09 microg/dl) when compared with controls (0.78+/-0.08 microg/dl, p<0.05 l), and it was independent of pain intensity and Mental health (MH) scores in SF-36. We concluded that women with endometriosis and chronic pelvic pain show low concentrations of salivary cortisol and a high level of perceived stress, associated with a poor quality of life. Whether the hypocortisolism was an adaptive response to the aversive symptoms of the disorder or a feature related to the etiology of endometriosis remains to be elucidated.     

Effects of stress and sex on acquisition and consolidation of human fear conditioning

We examined the relationship between stress hormone (cortisol) release and acquisition and consolidation of conditioned fear learning in healthy adults. Participants underwent acquisition of differential fear conditioning, and consolidation was assessed in a 24-h delayed extinction test. The acquisition phase was immediately followed by an 11-min psychosocial stress period (arithmetic test combined with a public speech). Salivary cortisol was sampled at various time points before and after acquisition and retention of fear conditioning. Results showed two effects of endogenous cortisol. Post-acquisition cortisol correlated with fear acquisition in male but not female participants. In addition, post-acquisition cortisol correlated with consolidation of fear but only in those participants with high cortisol levels. We conclude that in the short term, a robust and sexually dimorphic relationship exists between fear learning and stress hormone levels. For those participants whose fear learning is accompanied by high stress hormone levels, a long-term relationship exists between cortisol release and memory consolidation. These short-term and long-term effects may relate to the differential involvement of mineralocorticoid and glucocorticoid receptor subtypes, respectively. The findings have implications for understanding the role of stress, sex, and hormones in different stages of fear learning and memory.     

Glucocorticoid receptor antagonists: new tools to investigate disorders characterized by cortisol hypersecretion

Increased cortisol levels have been observed in patients suffering from a number of metabolic and psychiatric disorders. In some of these disorders a causal relationship has been suggested between the increased cortisol secretion and the observed clinical phenomena. Glucocorticoid receptor antagonists which block cortisol effects might have a benefit in both the diagnosis and treatment of these disorders. Selective glucocorticoid receptor antagonists with in vivo potency have not been described thus far, partly due to the similarity between the glucocorticoid and progesterone receptors. In the present studies, we report on three different chemical classes derived from the glucocorticoid/progestagen antagonist RU486. Selected compounds from the classes 11-monoaryl steroids, 11,21-bisaryl steroids and 11-aryl, 16-hydroxy steroids proved to be selective glucocorticoid receptor binders with in vivo antagonistic activity. Most compounds were able to pass the blood-brain barrier. These compounds offer the opportunity to investigate and possibly treat patients with a disturbed hypothalamus-pituitary-adrenal axis without side effects caused by an antiprogestagenic action.     

The effects of cortisol increase on long-term memory retrieval during and after acute psychosocial stress

In this study the effects of stress-induced cortisol increases on long-term memory retrieval during and after acute psychosocial stress were examined. Seventy male students were exposed to either a psychosocial stress task or to a non-stressful control task. During and after this task, retrieval was tested for idiosyncratic emotionally negative and neutral word pair associations that were learned 1 day or 5 weeks earlier. Within the stress condition, retrieval of negative words, 5 weeks after learning, was impaired both during and after the stress task compared to the control group. Further, during the stress task, when sympathetic activity was enhanced, impaired retrieval of both neutral and emotional words was significantly related to enhanced cortisol response. In contrast, after the stress task, when cortisol levels were still increased but sympathetic activity was low again, no association was found between cortisol increase and retrieval of either neutral or emotional material. These results are in line with the previous animal research showing that when arousal is high, cortisol increase can impair memory retrieval.     

Consistency in Physiological Stress Responses and Electromyographic Activity during Induced Stress Exposure in Women and Men

Physiological responses serve the role as objective indicators of stress as well as a link between psychosocial stress and various health outcomes. The aim of the present exposure session was to compare different physiological stress responses (systolic and diastolic blood pressure, heart rate, urinary epinephrine and norepinephrine, salivary cortisol) as well as trapezius muscle activity, measured by surface electromyography, during mental and physical stress in 11 women and ten men. The results show significantly increased activity in all measures but cortisol and significant associations between sympathetic arousal and EMG activity. The association between sympathetic arousal and muscle activity is of importance for understanding the high prevalence of musculoskeletal disorders in mentally stressful but physically light work tasks. Men had higher blood pressure and a more pronounced increase in epinephrine output than women, whereas women had higher heart rate. It was concluded that sympathetic activity is more sensitive to moderately intense stress exposure than pituitary adrenocortical (cortisol) activity and that men respond to performance stress with more epinephrine output than women. Although the correlations between the different indicators of sympathetic arousal were high, together they could still only explain 30-70% of the inter-individual variance. Thus, several parameters are needed in order to obtain a reliable measure of sympathetic activity.     

Neural bases of moderation of cortisol stress responses by psychosocial resources

Psychosocial resources have been tied to lower psychological and biological responses to stress. The present research replicated this relationship and extended it by examining how differences in dispositional reactivity of certain neural structures may underlie this relationship. Two hypotheses were examined: (a) psychosocial resources are tied to decreased sensitivity to threat and/or (b) psychosocial resources are associated with enhanced prefrontal inhibition of threat responses during threat regulation. Results indicated that participants with greater psychosocial resources exhibited significantly less cortisol reactivity following a stress task, as predicted. Analyses using functional magnetic resonance imaging revealed that psychosocial resources were associated with greater right ventrolateral prefrontal cortex and less amygdala activity during a threat regulation task but were not associated with less amygdala activity during a threat sensitivity task. Mediational analyses suggest that the relation of psychosocial resources to low cortisol reactivity was mediated by lower amygdala activity during threat regulation. Results suggest that psychosocial resources are associated with lower cortisol responses to stress by means of enhanced inhibition of threat responses during threat regulation, rather than by decreased sensitivity to threat.     

Stress, glucocorticoids, and memory: a meta-analytic review

Although a strong psychoneuroendocrine linkage exists between stress, glucocorticoids and memory, the relationship is not always straightforward. Eighty-eight effect sizes and 1642 participants from 28 studies were meta-analyzed for the effects of stress on memory performance and glucocorticoid activation. Analyses showed that stress was associated with glucocorticoid activation and declarative memory decline. In animal studies, predator stress affected memory performance more than physical stress. In human studies, males showed higher cortisol levels than females in response to stress. Further, the correlation between cortisol levels and memory deficits was stronger in studies using laboratory stressors than those examining long term effects of chronic exposure to rising basal levels of glucocorticoids and chronic life stressors. It was concluded that, although the relationship between stress, glucocorticoids, and memory loss was empirically supported, there were other factors, such as stress condition and gender, as well as individual differences within groups, that influenced the association between these variables, and warrant further examination.     

Physical fitness and prior physical activity are both associated with less cortisol secretion during psychosocial stress

Background: Evidence linking fitness and decreased psychosocial stress comes from studies of athletes and typically relies upon self-report measures. Furthermore, there is little evidence regarding the impact of physical activity (PA) prior to a stressor. The aims of this study were to determine whether fitness and prior PA influence cortisol concentrations during psychosocial stress.

Methods: Seventy-five non-athletic participants took part in a submaximal walk prior to the Trier Social Stress Test for Groups (TSST-G). During the walk, fitness was assessed using heart rate (HR). A further 89 participants took part in the TSST-G without the walk. Stress responsiveness was assessed using salivary cortisol collected at 10-min intervals on seven occasions.

Results: Hierarchical multiple regression revealed that average walking HR accounted for 9% of the variance in cortisol secretion (P?=?.016), where a higher HR was associated with higher cortisol secretion. Between-subjects ANCOVA revealed that the walking group had a significantly lower cortisol secretion than the non-walking group (P?=?.009).

Conclusions: These findings indicate that fitter individuals have reduced cortisol secretion during psychosocial stress. They also indicate that prior PA can reduce cortisol concentrations during psychosocial stress and are suggestive of a role of PA in reducing the impact of stress on health.     

Stress administered prior to encoding impairs neutral but enhances emotional long-term episodic memories

Stressful events frequently comprise both neutral and emotionally arousing information, yet the impact of stress on emotional and neutral events is still not fully understood. The hippocampus and frontal cortex have dense concentrations of receptors for stress hormones, such as cortisol, which at high levels can impair performance on hippocampally dependent memory tasks. Yet, the same stress hormones can facilitate memory for emotional information, which involves interactions between the hippocampus and amygdala. Here, we induced psychosocial stress prior to encoding and examined its long-term effects on memory for emotional and neutral episodes. The stress manipulation disrupted long-term memory for a neutral episode, but facilitated long-term memory for an equivalent emotional episode compared with a control condition. The stress manipulation also increased salivary cortisol, catecholamines as indicated by the presence of alpha-amylase, heart rate, and subjectively reported stress. Stressed subjects reported more false memories than nonstressed control subjects, and these false memories correlated positively with cortisol levels, providing evidence for a relationship between stress and false memory formation. Our results demonstrate that stress, when administered prior to encoding, produces different patterns of long-term remembering for neutral and emotional episodes. These differences likely emerge from differential actions of stress hormones on memory-relevant regions of the brain.     

Effect of stress on hippocampal nociceptin expression in the rat

Nociceptin/orphanin FQ (N/OFQ) peptide and its receptor are not only ubiquitously expressed in mammalian brain and spinal cord but are also abundant in limbic structures, particularly in the hippocampus. The widespread distribution of N/OFQ reflects the broad spectrum of its biological actions such as nociception, food intake, spontaneous locomotor activity, and learning and memory processes. Since the hippocampus is involved in the control of adrenocortical activity, its role in stress-related phenomena is well characterized. In male Wistar rats, we first examined the effects of acute restraint stress (120?min) on the brain immunohistochemical localization of N/OFQ. The analysis carried out on sections obtained at the onset of stress revealed enhanced expression of N/OFQ in CA1, CA3, and the dentate gyrus as well as increased plasma corticosterone concentrations. Next, we examined whether endogenous glucocorticoid hormone plays a role in the modulation of hippocampal N/OFQ expression in response to stress. To this end, rats were injected with corticosterone (1?mg/kg) or subjected to restraint stress 1 week after adrenalectomy. Two hours after corticosterone administration, plasma glucocorticoid concentrations were comparable to those observed after restraint stress, while N/OFQ expression had significantly increased in all the hippocampal subfields examined. By contrast, in adrenalectomized rats, stress did not modify protein expression. These results confirm that stress can affect N/OFQ expression and that glucocorticoids may constitute hormonal mediators of this complex interplay.     

Better not to deal with two tasks at the same time when stressed? Acute psychosocial stress reduces task shielding in dual-task performance

A major control demand in successful dual-task performance is the task-specific separation of task-goal representations and of the related stimulus-response translation processes. In the present study, we investigated how these cognitive control processes of task shielding are affected by acute psychosocial stress. Fifty-six healthy participants were exposed to either an acute psychosocial stressor (the Trier Social Stress Test) or a standardized control situation prior to a dual task. Task shielding was assessed by analyzing the interference of Task 2 processing on prioritized Task 1 performance. Following successful stress induction, as indicated by increases in salivary α-amylase (sAA) and cortisol that reflect increases in sympathetic nervous system and hypothalamus-pituitary-adrenal (HPA) axis activity, respectively, stressed individuals displayed reduced task shielding relative to controls. This result was further substantiated by a correlation between treatment-related increase in cortisol, but not sAA, and between-task interference, suggesting a potential role of the HPA stress response for the development of the observed effects. As an additional finding, when the volunteers were categorized with regard to their action-state orientation, their orientation did not interact with stress but did reveal generally increased between-task interference, and thus inferior task shielding, for state-oriented as compared to action-oriented individuals.     

Differentiating the impact of episodic and chronic stressors on hypothalamic-pituitary-adrenocortical axis regulation in young women.

OBJECTIVE: The goal of this study was to examine the impact of episodic stress and chronic interpersonal stress on indices of HPA regulation. To explore the potential downstream consequences of altered HPA dynamics, the authors also assessed indicators of metabolic control and systemic inflammation. DESIGN: One hundred four medically healthy women between the ages of 15 and 19 participated. Following an in-depth interview of life stress, a sample of blood was drawn through antecubital venipuncture. Over the course of the next 2 days, participants gathered salivary cortisol samples. MAIN OUTCOME MEASURES: Cortisol morning response, cortisol daily output, glucocorticoid receptor (GR) mRNA, C-reactive protein (CRP), insulin, and glucose. RESULTS: The simple presence of episodic stress or chronic interpersonal stress was not reliably associated with cortisol output, GR mRNA, insulin, or glucose. When women were exposed to an episodic stressor in the midst of chronic stress they showed increased cortisol output and reduced expression of GR mRNA. By contrast, when women had low levels of chronic stress, episodic events were associated with decreased cortisol output and increased GR mRNA. Episodic and chronic stress also interacted to predict CRP, but not insulin or glucose. CONCLUSIONS: The impact of episodic stress is accentuated in the midst of chronic interpersonal stress and diminished in its absence. Simultaneous exposure to episodic and chronic stress may create wear and tear on the body, whereas exposure to episodic stress in the context of a supportive environment may toughen the body, protecting it against subsequent stressors.     

Chronic psychosocial stress increases the risk for inflammation-related colon carcinogenesis in male mice

Patients with inflammatory bowel diseases (IBDs) have a higher risk of developing colorectal cancer (CRC) than the general population. Furthermore, chronic psychosocial stress increases the likelihood of developing IBD and multiple types of malignant neoplasms, including CRC. Here, for the first time, we investigate the effects of chronic psychosocial stress in male mice on an artificially induced CRC, by employing the chronic subordinate colony (CSC) housing paradigm in combination with the reliable azoxymethane (AOM)/dextran sodium sulfate (DSS) CRC model. Colonoscopy revealed that CSC mice showed accelerated macroscopic suspect lesions. In addition, more CSC mice developed low-grade dysplasia (LGD) and/or high-grade dysplasia (HGD) in the colonic tissue compared to the single-housed control mice (SHC). CSC mice showed an increased number of Ki67+ and a decreased number of terminal deoxynucleotidyl transferase dUTP nick end labeling epithelial cells in colonic tissue. Colonic liver receptor homolog-1 (LRH-1), cyclooxygenase II (COXII), tumor necrosis factor, forkhead box P3 (FoxP3) mRNA as well as colonic ?-catenin, COXII, and LRH-1 protein expression were also increased in CSC compared with SHC mice. Although the number of CD4+ Th cells was increased, a tendency toward a decreased colonic interferon-γ (IFN-γ) mRNA expression was observed. Furthermore, despite an increased percentage of CD3+ cells and CD3+/FoxP3+ double-positive cells within mesenteric lymph node cells of CSC mice, IFN-γ secretion from these cells was unaffected. Altogether, our results suggest that chronic psychosocial stress increases the risk for AOM/DSS-induced and, thus, inflammation-related CRC. Finally, assessment of additional time points may test whether the shift from tumor-protective Th1 cell to regulatory T-cell immunity represents a consequence of increased carcinogenesis or a causal factor involved in its development.     

Consistency in physiological stress responses and electromyographic activity during induced stress exposure in women and men

Physiological responses serve the role as objective indicators of stress as well as a link between psychosocial stress and various health outcomes. The aim of the present exposure session was to compare different physiological stress responses (systolic and diastolic blood pressure, heart rate, urinary epinephrine and norepinephrine, salivary cortisol) as well as trapezius muscle activity, measured by surface electromyography, during mental and physical stress in 11 women and ten men. The results show significantly increased activity in all measures but cortisol and significant associations between sympathetic arousal and EMG activity. The association between sympathetic arousal and muscle activity is of importance for understanding the high prevalence of musculoskeletal disorders in mentally stressful but physically light work tasks. Men had higher blood pressure and a more pronounced increase in epinephrine output than women, whereas women had higher heart rate. It was concluded that sympathetic activity is more sensitive to moderately intense stress exposure than pituitary adrenocortical (cortisol) activity and that men respond to performance stress with more epinephrine output than women. Although the correlations between the different indicators of sympathetic arousal were high, together they could still only explain 30–70% of the inter-individual variance. Thus, several parameters are needed in order to obtain a reliable measure of sympathetic activity.     

The psychobiology of trait shame in young women: extending the social self preservation theory

OBJECTIVE: The social self preservation theory (SSPT) proposes that social evaluative threat evokes the emotion of shame, which then shapes a coordinated psychobiological response. While this is supported in acute stress studies, there is no data on chronic experiences of shame. DESIGN: We investigated the association of trait shame with activity of the hypothalamic-pituitary-adrenal (HPA) axis, of the sympathetic nervous system (SNS), and regulation of inflammation in n = 56 young women. MAIN OUTCOME MEASURES: Daily profiles of salivary cortisol and alpha-amylase were assessed as indices of HPA axis and SNS activity, respectively. Inflammatory regulation was assessed by lipopolysaccharide-stimulated production and glucocorticoid inhibition of interleukin-6 in vitro. RESULTS: Trait shame was associated with SNS (r = .49; p = .001), but not HPA activity (r = .14; ns). Shame was associated with inflammatory activity (r = .35; p = .006) and glucocorticoid sensitivity (r = -0.43; p = .001). Relationships were not mediated by HPA and SNS activity. CONCLUSIONS: Results support SSPT predictions with respect to chronic shame experience and inflammation. Results further suggest the importance of SNS activation related to shame, and the possibility that HPA activation may be limited acute experiences of shame.     

慢性军事应激致军人海马形态、认知功能和应对方式的变化

通过对572名连续4~16个月高强度军事训练的军人进行SCL-90测评, 研究慢性军事应激条件下军人海马形态、认知、心理特质和特质应对方式的变化特征。将其中l7例焦虑因子分≥3分者(焦虑或伴焦虑)设为研究组(A), 并以匹配法设对照组(B)。检测两组军人血皮质醇, 并用MRI观察海马形态、检测简单和复杂认知作业功能、以STAI测评状态-特质焦虑及以CCSQ测评应对方式, 探讨两组对应变化。研究结果显示：(1)血皮质醇：A、B组均高于正常水平, 有差异显著, A组显著高于B组。(2)海马形态：A组与B组MRI海马形态标准化后, A组海马形态显著萎缩, 与B组相比有显著性差异, 但各组每个同体的左右两侧之间相比无显著性差异。(3)认知作业功能：A组简单认知作业成绩与B组无显著差异, 但复杂认知作业成绩与B组相比有显著性差异。(4)状态-特质焦虑：A组的状态焦虑、特质焦虑分别与B组和常模比较均有显著变化, B组与常模相比状态焦虑变化显著, 特质焦虑变化不显著。(5)应对方式：A组积极应对方式平均值低于B组和常模并有显著性差异, B组高于常模; A组消极应对方式平均值高于B组和常模且有非常显著性差异, B组与常模无显著改变。结论 在慢性军事应激条件下, 特质焦虑个体的海马形态出现双侧萎缩, 复杂认知功能下降, 更易发生状态焦虑, 行为取向表现出积极应对方式降低、消极应对方式增加。     

Psychosocial stress enhances time-based prospective memory in healthy young men

Forgetting of intentions (such as to take one's medication) is the most frequent everyday memory failure. No study so far has looked into the possible consequences stress might exert on memory for intentions (i.e., prospective memory). Twenty healthy young male adults were exposed to a psychosocial stress test and a non-stress condition. After a delay of 15 min, a time- and an event-based prospective memory task were administered during the peak of cortisol concentrations. Results show that participants performed significantly better in the time-based memory task after stress in comparison to the non-stress condition. In contrast, there was no stress effect on event-based prospective memory. The results demonstrate that prospective memory might be enhanced when participants are exposed to stress prior to the memory task and that this effect is associated to stress-related glucocorticoid effects.