Perioperative anxiety and length of hospital stay after caesarean section - A cohort study.

OBJECTIVE: The caesarean section is one of the most frequently performed surgeries. Due to growing economic challenges, hospitals are encouraged to improve their cost-efficiency. One factor that influences hospital costs of caesarean sections is a prolonged hospital stay. STUDY DESIGN: The aim of the current prospective study was to investigate psychosocial factors, with an emphasis on anxiety, and sociodemographic factors that are associated with longer hospital stay after caesarean sections with no medical complications. Data of 195 women who gave birth by caesarean section was analyzed. As possible predictors anxiety levels measured pre-, peri- and postoperative as well as age, parity (primiparous/multiparous), repeated caesarean (yes/no), BMI (<30/ ≥30), STAI-Trait scores, duration of surgery, PH arterial and Apgar 5 min. were entered into a backward linear regression with duration of hospital stay as the dependent factor. RESULTS: The analysis revealed that higher age, primiparity as well as higher anxiety scores during the postoperative phase are significant factors associated with prolonged hospital stay. The significant model explains 22.1 % of the variance. CONCLUSION: The results should sensitize the medical team to these risk factors in order to improve patients' recovery and shorten hospital stays.

Comparing the course of anxiety in women receiving their first or repeated caesarean section: A prospective cohort study.

BACKGROUND: Around 30% of births are through caesarean section and repetition rates for receiving a caesarean section are high. AIM: The aim of the prospective study was to compare the course of anxiety in women undergoing their first caesarean section and women experiencing a repeated caesarean section. PARTICIPANTS: 304 women with an indication for an elective caesarean section took part. 155 received their first caesarean section and 149 received a repeated caesarean section. METHODS: In order to measure the course of anxiety on the day of the caesarean section subjective anxiety levels were measured and saliva samples for cortisol determination were taken at admission, during skin closure and two hours after the surgery. Blood pressure and heart rate were documented at skin incision and skin closure. RESULTS: Women experiencing their first caesarean section displayed significantly higher anxiety levels compared to women with a repeated caesarean section. Scores of the STAI-State and visual analogue scale for anxiety differed significantly at admission (p=.006 and p<.001) and heart rate and alpha amylase levels were significantly higher at skin closure (p=.027 and p=.029). CONCLUSION: The results show that previous experience with a caesarean section has a soothing effect. The study aims to sensitize surgeons, anesthetists, nurses and midwives when treating women receiving a caesarean section and encourage them to incorporate soothing interventions, especially for women receiving their first caesarean section to reduce anxiety levels and consequently improve postoperative recovery and patients' satisfaction.

A Functional Near-Infrared Spectroscopy Study on the Cortical Haemodynamic Responses During the Maastricht Acute Stress Test.

In order to better understand stress responses, neuroimaging studies have investigated the underlying neural correlates of stress. Amongst other brain regions, they highlight the involvement of the prefrontal cortex. The aim of the present study was to explore haemodynamic changes in the prefrontal cortex during the Maastricht Acute Stress Test (MAST) using mobile functional Near-Infrared Spectroscopy (fNIRS), examining the stress response in an ecological environment. The MAST includes a challenging mental arithmic task and a physically stressful ice-water task. In a between-subject design, participants either performed the MAST or a non-stress control condition. FNIRS data were recorded throughout the test. Additionally, subjective stress ratings, heart rate and salivary cortisol were evaluated, confirming a successful stress induction. The fNIRS data indicated significantly increased neural activity of brain regions of the dorsolateral prefrontal cortex (dlPFC) and the orbitofrontal cortex (OFC) in response to the MAST, compared to the control condition. Furthermore, the mental arithmetic task indicated an increase in neural activity in brain regions of the dlPFC and OFC; whereas the physically stressful hand immersion task indicated a lateral decrease of neural activity in the left dlPFC. The study highlights the potential use of mobile fNIRS in clinical and applied (stress) research.

Cell-free DNA release under psychosocial and physical stress conditions.

The understanding of mechanisms linking psychological stress to disease risk depend on reliable stress biomarkers. Circulating cell-free DNA (cfDNA) has emerged as a potential biomarker of cellular stress, aging, inflammatory processes, and cell death. Recent studies indicated that psychosocial stress and physical exercise might also influence its release. We compared the effects of acute psychosocial and physical exercise stress on cfDNA release by exposing 20 young, healthy men to both an acute psychosocial laboratory stressor and an acute physical exercise stressor. Venous blood and saliva samples were collected before and after stress exposure. Cell-free DNA was extracted from plasma and quantified by qPCR. Furthermore, cfDNA fragment length was analyzed and cfDNA methylation patterns were assayed across time. In addition, release of stress hormones and subjective stress responses were measured. Results showed a twofold increase of cfDNA after TSST and fivefold increase after exhaustive treadmill exercise, with an overabundance of shorter cfDNA fragments after physical exhaustion. Interestingly, cell-free mitochondrial DNA showed similar increase after both stress paradigms. Furthermore, cfDNA methylation signatures-used here as a marker for diverse cellular origin-were significantly different post stress tests. While DNA methylation decreased immediately after psychosocial stress, it increased after physical stress, suggesting different cellular sources of active DNA release. In summary, our results suggest stimulus and cell-specific regulation of cfDNA release. Whereas the functional role of stress-associated cfDNA release remains elusive, it might serve as a valuable biomarker in molecular stress research as a part of the psychophysiological stress response.

Psychosocial stress differentially affects emotional empathy in women with borderline personality disorder and healthy controls.

OBJECTIVE: Deficits in empathy, an important part of social cognition, have been described in patients with borderline personality disorder (BPD). Importantly, psychosocial stress enhances emotional empathy in healthy participants. However, it remains unknown whether stress affects empathy in BPD. METHOD: We randomized 47 women with BPD and 47 healthy women to either the Trier Social Stress Test or a control condition. Subsequently, all participants underwent the Multifaceted Empathy Test (MET), a measure of cognitive and emotional facets of empathy. RESULTS: Across groups, stress resulted in a significant increase in cortisol and stress ratings. There was a significant stress × group interaction for emotional empathy (Fdf1,92 = 5.12, P = 0.04, ηp2 = 0.05). While there was no difference between patients with BPD and healthy participants after the control condition, patients with BPD had significantly lower emotional empathy scores after stress compared to healthy individuals. There were no effects for cognitive empathy. CONCLUSION: The current finding provides first evidence that stress differentially affects emotional empathy in patients with BPD and healthy individuals such that patients with BPD showed reduced emotional empathy compared to healthy women after stress. Given the strong impact of stress on acute psychopathology in patients with BPD, such a response may exacerbate interpersonal conflicts in stress contexts and may be an important target for therapeutic interventions.

The stress hormone cortisol blocks perceptual learning in humans.

Cortisol, the primary glucocorticoid (GC) in humans, influences neuronal excitability and plasticity by acting on mineralocorticoid and glucocorticoid receptors. Cellular studies demonstrated that elevated GC levels affect neuronal plasticity, for example through a reduction of hippocampal long-term potentiation (LTP). At the behavioural level, after treatment with GCs, numerous studies have reported impaired hippocampal function, such as impaired memory retrieval. In contrast, relatively little is known about the impact of GCs on cortical plasticity and perceptual learning in adult humans. Therefore, in this study, we explored the impact of elevated GC levels on human perceptual learning. To this aim, we used a training-independent learning approach, where lasting changes in human perception can be induced by applying passive repetitive sensory stimulation (rss), the timing of which was determined from cellular LTP studies. In our placebo-controlled double-blind study, we used tactile LTP-like stimulation to induce improvements in tactile acuity (spatial two-point discrimination). Our results show that a single administration of hydrocortisone (30mg) completely blocked rss-induced changes in two-point discrimination. In contrast, the placebo group showed the expected rss-induced increase in two-point discrimination of over 14%. Our data demonstrate that high GC levels inhibit rss-induced perceptual learning. We suggest that the suppression of LTP, as previously reported in cellular studies, may explain the perceptual learning impairments observed here.

Acute stress influences the discrimination of complex scenes and complex faces in young healthy men.

The stress-induced release of glucocorticoids has been demonstrated to influence hippocampal functions via the modulation of specific receptors. At the behavioral level stress is known to influence hippocampus dependent long-term memory. In recent years, studies have consistently associated the hippocampus with the non-mnemonic perception of scenes, while adjacent regions in the medial temporal lobe were associated with the perception of objects, and faces. So far it is not known whether and how stress influences non-mnemonic perceptual processes. In a behavioral study, fifty male participants were subjected either to the stressful socially evaluated cold-pressor test or to a non-stressful control procedure, before they completed a visual discrimination task, comprising scenes and faces. The complexity of the face and scene stimuli was manipulated in easy and difficult conditions. A significant three way interaction between stress, stimulus type and complexity was found. Stressed participants tended to commit more errors in the complex scenes condition. For complex faces a descriptive tendency in the opposite direction (fewer errors under stress) was observed. As a result the difference between the number of errors for scenes and errors for faces was significantly larger in the stress group. These results indicate that, beyond the effects of stress on long-term memory, stress influences the discrimination of spatial information, especially when the perception is characterized by a high complexity.

Stress and Memory: A Selective Review on Recent Developments in the Understanding of Stress Hormone Effects on Memory and Their Clinical Relevance.

Stress causes a neuroendocrine response cascade, leading to the release of catecholamines and glucocorticoids (GCs). GCs influence learning and memory by acting on mineralocorticoid (MR) and glucocorticoid (GR) receptors. Typically, GCs enhance the consolidation of memory processing at the same time as impairing the retrieval of memory of emotionally arousing experiences. The present selective review addresses four recent developments in this area. First, the role of the endocannabinoid system in mediating the rapid, nongenomic effects of GCs on memory is illustrated in rodents. Subsequently, studies on the impact of the selective stimulation of MRs on different memory processes in humans are summarised. Next, a series of human experiments on the impact of stress or GC treatment on fear extinction and fear reconsolidation is presented. Finally, the clinical relevance of the effects of exogenous GC administration is highlighted by the description of patients with anxiety disorders who demonstrate an enhancement of extinction-based therapies by GC treatment. The review highlights the substantial progress made in our mechanistic understanding of the memory-modulating properties of GCs, as well as their clinical potential.

Cerebellar vermis contributes to the extinction of conditioned fear.

The cerebellum is known to contribute to the acquisition and retention of conditioned motor and emotional responses. Eyeblink conditioning and fear conditioning have been studied in greatest detail. Whereas a considerable number of studies have shown that the cerebellum is also involved in extinction of conditioned eyeblink responses, the likely contribution of the cerebellum to extinction of conditioned fear responses has largely been ignored. In the present study, we analyzed functional brain imaging data (fMRI) of previous work investigating extinction of conditioned fear in 32 young and healthy men, in which event-related fMRI analysis did not include the cerebellum. This dataset was analyzed using a spatial normalization method optimized for the cerebellum. During fear acquisition, an unpleasant electric shock (unconditioned stimulus; US) was paired with one of two pictures of geometrical figures (conditioned stimulus; CS+), while the other picture (CS-) was never paired with the US. During extinction, CS+ and CS- were presented without the US. During the acquisition phase, the fMRI signal related to the CS+ was significantly higher in hemispheric lobule VI in early compared to late acquisition (p<.05, permutation corrected). During the extinction phase, the fMRI signal related to the contrast CS+>CS- was significantly higher within the anterior vermis in early compared to late extinction (p<.05, permutation corrected). The present data show that the cerebellum is not only associated with the acquisition but also with the extinction of conditioned fear.

No benefit adding eleutherococcus senticosus to stress management training in stress-related fatigue/weakness, impaired work or concentration, a randomized controlled study.

INTRODUCTION: Plant adaptogens are traditionally used for stress-related symptoms, but clinical evidence is inconsistent. This trial explored the effects of 120 mg/day Eleutherococcus senticosus root extract (ES), 2-day professional stress management training (SMT) and a combination of both (COM). METHODS: 144 participants suffering from asthenia and reduced working capacity related to chronic stress were randomized to the treatments. Validated scales and tests were used to investigate cognitive performance; feeling stressed; fatigue and exhaustion; alertness, restlessness and mood; quality of life and sleep; physical complaints and activities; and physiological stress parameters including cortisol awakening response (CAR), at baseline, after 2 and 8 weeks of treatment (German Clinical Trials Register DRKS00000692). RESULTS: Almost all parameters improved significantly over time without group differences. Significant differences were found in mental fatigue and restlessness, both in favor of COM vs. ES. COM was not superior to SMT in any parameter at week 8. An attenuation of the CAR was seen at week 2 without group differences. All treatments were well tolerated. DISCUSSION: Effects of adding ES to SMT are, if any, negligible.

Effects of cortisol on memory in women with borderline personality disorder: role of co-morbid post-traumatic stress disorder and major depression.

BACKGROUND: Stress and cortisol administration are known to have impairing effects on memory retrieval in healthy humans. These effects are reported to be altered in patients with major depressive disorder (MDD) and post-traumatic stress disorder (PTSD) but they have not yet been investigated in borderline personality disorder (BPD). METHOD: In a placebo-controlled cross-over study, 71 women with BPD and 40 healthy controls received either placebo or 10 mg of hydrocortisone orally before undertaking a declarative memory retrieval task (word list learning) and an autobiographical memory test (AMT). A working memory test was also applied. RESULTS: Overall, opposing effects of cortisol on memory were observed when comparing patients with controls. In controls, cortisol had impairing effects on memory retrieval whereas in BPD patients cortisol had enhancing effects on memory retrieval of words, autobiographical memory and working memory. These effects were most pronounced for specificity of autobiographical memory retrieval. Patients with BPD alone and those with co-morbid PTSD showed this effect. We also found that co-morbid MDD influenced the cortisol effects: in this subgroup (BPD + MDD) the effects of cortisol on memory were absent. CONCLUSIONS: The present results demonstrate beneficial effects of acute cortisol elevations on hippocampal-mediated memory processes in BPD. The absence of these effects in patients with co-morbid MDD suggests that these patients differ from other BPD patients in terms of their sensitivity to glucocorticoids (GCs).

Psychosocial stress exposure impairs memory retrieval in children.

Negative consequences of stress on working memory and delayed memory retrieval have been observed in adult humans. Little is known about the occurrence of similar effects in children. Forty-four German full-term children, aged 8-10 years, were randomly assigned to a stressful (Trier Social Stress Test for Children--TSST-C) or to a non-stressful control condition. Afterwards, delayed memory retrieval was tested using a computerized version of the well-known card game "Memory". It contained positive, neutral and negative stimuli. In addition, working memory of verbal and non-verbal material was assessed. The stressed children showed pronounced cortisol increases accompanied by a decrease in mood. Children exposed to the stressor performed poorer in the delayed memory retrieval test (memory card game). They committed more errors. No differences were found for working memory. The stress-induced memory retrieval impairment mirrors findings in adults. In contrast, the missing working memory effects could suggest developmental differences in stress sensitivity.

Neuroendocrine and psychometric evaluation of a placebo version of the 'Trier Social Stress Test'.

The "Trier Social Stress Test" (TSST) is one of the most prominent laboratory stress paradigms. It is often used to investigate the effects of stress on cognitive or affective parameters. Such studies need a non-stress control condition. However, control conditions currently employed are often rather ill defined and do not parallel important modulating variables, e.g., physical or cognitive load of the TSST. We here introduce a placebo version of the TSST, which contains a free speech and a simple mental arithmetic task without uncontrollability and social-evaluative threat. In two studies, this control condition was evaluated using salivary markers of stress reactivity (cortisol and alpha-amylase) and a questionnaire for anticipatory cognitive stress appraisal (PASA). In experiment 1 participants who were treated with the placebo condition showed no cortisol response and a small, but significant salivary alpha-amylase (sAA) response. Both responses were significantly smaller than those of TSST-treated participants. The placebo-treated participants also rated the treatment situation as less stressful. In experiment 2 a crossover study with the use of an intercom to instruct the participants and ensure their compliance was conducted. Again there was a strong cortisol response to the TSST, which differed significantly from the cortisol levels observed during the placebo condition. Importantly the cortisol response was not influenced by treatment order (TSST or placebo first). However, in this study we found similar reactions between TSST- and placebo-treated participants with regard to sAA-response. We suggest that the introduced placebo protocol for the TSST is a promising tool for future psychobiological research. The exact procedure for a given experiment should be tailored to the specific needs of the empirical question studied.

Neuroendocrine stress responses to an oral academic examination: No strong influence of sex, repeated participation and personality traits.

Public speaking tasks have been widely used as laboratory stressors in human research. Fewer studies have investigated similar real life situations like oral examinations and results have been inconsistent. The present study investigated salivary cortisol (as a marker of hypothalamus-pituitary-adrenal (HPA) activity) and salivary alpha-amylase (sAA as a marker of sympathetic nervous system (SNS) activity) within the context of a university examination. Subjects were 40 undergraduate students who participated in an oral examination. Of these, 20 also participated in a second examination within a few weeks. Cortisol and sAA were measured immediately before and after the examination and on a control day. Additionally, subjects filled out personality questionnaires. A strong anticipatory increase in salivary cortisol and sAA as well as more modest further increases between the pre- and post-measurements were detected during the examination. Sex or oral contraceptive use had no influence on either measure. In addition, no significant differences between the first and second examination were observed. The findings indicate the neuroendocrine stress responses to laboratory stressors and to heralded real life stressors as well as the modulatory variables involved differ from each other.

Hippocampal volume and cognitive performance in long-standing Type 1 diabetic patients without macrovascular complications.

AIMS: Hippocampal atrophy and memory deficits have been reported in Type 2 diabetes. Whether similar alterations occur in Type 1 diabetes is currently unknown. METHODS: In a case-control design, 13 Type 1 diabetic patients with at least 10 years' duration of disease, but free from clinical signs of macrovascular disease, were compared with age- and gender-matched control subjects. Hippocampal volume and measures of global cerebral cerebrospinal fluid (CSF) were determined from magnetic resonance imaging (MRI) scans. Cognitive functions were assessed using four neuropsychological tests. Mood and depression were measured by questionnaires. RESULTS: Hippocampal volume and memory did not differ between Type 1 diabetic patients and control subjects. However, a significantly increased amount of cerebral CSF suggestive of mild cerebral atrophy was observed in the patients. In addition, deficits in psychomotor speed and selective attention were apparent. Eleven of 13 patients had retinopathy and/or nephropathy. Findings were unrelated to cerebrovascular disease, white matter disease or silent strokes. CONCLUSIONS: Results from our small study in Type 1 diabetic patients do not support findings from previous studies of Type 2 diabetic patients demonstrating reductions in hippocampal volume and impaired memory. On the contrary, we observed evidence for mild cerebral atrophy and impaired psychomotor speed and selective attention. This is in line with some previous studies in Type 1 diabetes. If replicated in larger studies, our findings would support the idea that the effects on brain function and structure differ between Type 1 and Type 2 diabetes.

Investigating the effects of estradiol or estradiol/progesterone treatment on mood, depressive symptoms, menopausal symptoms and subjective sleep quality in older healthy hysterectomized women: a questionnaire study.

Clinical studies have documented that estrogen treatment often ameliorates mood disturbances and depressive symptoms occurring during the menopausal transition. The relevance of gonadal hormones for mood and well-being in healthy older nondepressed women is less well understood. Fifty-one healthy hysterectomized women (mean age 64) participated in a placebo-controlled double-blind study on the effects of gonadal hormones on cognition. They received either estradiol (2 mg estradiol valerate), estradiol plus progesterone (100 mg micronized progesterone) or placebo. Mood, well being, menopausal symptoms, depressive symptoms and subjective sleep quality were measured at baseline and after 4 and 24 weeks of treatment using three questionnaires. Thirty-five women could be included into the final analysis. Strong increases in estradiol and progesterone levels occurred in response to the treatment. The two hormones, however, had no effects on mood, well-being, menopausal symptoms, sleep quality and depressive symptoms. The current small study suggests that older healthy nondepressed hysterectomized women do not react with positive or negative mood changes to estradiol or estradiol/progesterone treatment.

A meta-analytic review of the effects of acute cortisol administration on human memory.

Adrenal glucocorticoids (GC) secreted during stress modulate memory. Animal and human studies investigating the effects of acute GC treatment on memory have reported conflicting (enhancing as well as impairing) results. Several theories have been proposed to integrate these contradictory findings. Among the variables discussed are the timing of the GC treatment (before learning or before retrieval) and the time of day (morning versus afternoon). Here we review meta-analytically the results of 16 studies, which experimentally investigated the acute impact of cortisol treatment on human memory. The results revealed that the timing of GC application in the course of a study is a relevant variable which explains a substantial amount of the significant heterogeneity within the effect sizes. The studies which administered cortisol before retrieval (n = 4) reported a significant decrease (average effect size of d = -.49) in memory performance. Studies which administered cortisol before learning (n =12) found on average no effect (d = .08), but there is heterogeneity within these effect sizes. Further analysis on these experiments indicated that studies, which administered cortisol in the morning found a significant memory impairment (d = -.40), while studies conducted in the afternoon observed a small but significant memory enhancement (d = .22). This meta-analysis supports the idea that the timing of GC administration (before learning or before retrieval) is a major determinant of the effects of GCs on human memory. We discuss methodological limitations of the current analysis and suggest several areas for future research.

No changes in event-related potentials with estrogen or estrogen plus progesterone treatment in healthy older hysterectomized women: results from a double-blind, placebo-controlled study.

RATIONALE: The potential to improve cognition in older women with estrogen or estrogen/progesterone therapy is currently a matter of intense debate. Only a few studies conducted so far have used electrophysiological indicators of cognitive information processing as outcome measures in randomised placebo controlled studies. OBJECTIVES: This study was undertaken to measure changes in event-related potentials (ERPs) after short (4 weeks) or prolonged (24 weeks) hormone treatment in older women. METHODS: A randomised, double-blind, placebo-controlled study in hysterectomized older women (aged 58-75 years) was performed (n = 51). The participants received orally estradiol (2 mg estradiol valerate), estradiol plus progesterone (100 mg micronized progesterone) or placebo for 24 weeks. Using four different paradigms, early and late ERPs were assessed at baseline and after 4 and 24 weeks of treatment. RESULTS: Strong hormone increases were observed in the two active treatment groups. However, no significant effects on any of the assessed ERPs were observed in either of the two treatment groups. Similar non-significant findings were obtained for reaction time and error rate. CONCLUSIONS: Estradiol or estradiol/progesterone treatment appears to have no strong effects on several ERP markers of information processing in older hysterectomized women. The current negative findings might suggest a reduced sensitivity of the aged brain to gonadal steroids.

Cortisol and memory retrieval in humans: influence of emotional valence.

Glucocorticoids secreted in response to stress modulate memory in animals and humans. Studies in rodents suggest that glucocorticoids enhance memory consolidation but impair delayed retrieval. Similar negative effects on memory retrieval have been reported in humans. The human studies so far have not addressed the issue of emotional valence, which conceivably could modulate the effects of cortisol on retrieval. The present mini-review discusses two recent studies from our laboratories that investigate the influence of emotional valence on the retrieval-impairing effects of cortisol. Both studies observed that cortisol impaired retrieval and that emotional valence influenced these effects. For autobiographical memory the impairing effects were stronger for neutral than for emotional items, whereas for word retrieval the opposite pattern was observed (stronger effects on emotional words). Possible reasons for these results are the different memory domains tested as well as the different sex of the subjects. Future studies will address these issues, which are of relevance for psychiatric disorders such as posttraumatic stress disorder or major depression.