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.

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).

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.

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.

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.

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.

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.

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.

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.

Effects of a two-week physiological dehydroepiandrosterone substitution on cognitive performance and well-being in healthy elderly women and men.

The levels of dehydroepiandrosterone (DHEA) and its sulfate ester DHEAS decrease with age after a peak around 25 yr. Animal studies as well as the first studies in humans have generated the idea that DHEA replacement in elderly subjects may have beneficial effects on well-being and cognitive functions. In the present experiment 40 healthy elderly men and women (mean age, 69 yr) participated in a double blind, placebo-controlled DHEA substitution study. For 2 weeks subjects took 50 mg DHEA daily, followed by a 2-week wash-out period and a 2-week placebo period. The treatment sequence was randomized in a cross-over design. After 2 weeks of DHEA or placebo, psychological and physical well-being as well as cognitive performance were assessed using several questionnaires and neuropsychological tests. All subjects had low DHEAS baseline levels. DHEA substitution lead to a 5-fold increase in DHEAS levels in women (from 0.67 +/- 0.1 to 4.1 +/- 0.4 micrograms/mL; P < 0.001) and men (from 0.85 +/- 0.1 to 4.5 +/- 0.4 micrograms/mL; P < 0.001). DHEA, androstenedione, and testosterone levels also increased significantly in both sexes (all P < 0.001). No significant changes were observed in insulin-like growth factor I or insulin-like growth factor-binding protein-3 levels. DHEA replacement had no strong beneficial effect on any of the measured psychological or cognitive parameters. Only women tended to report an increase in well-being (P = 0.11) and mood (P = 0.10), as assessed with questionnaires. They also showed better performance in one of six cognitive tests (picture memory) after DHEA. However, after Bonferroni alpha adjustment, this difference was no longer significant. No such trend was observed in men (P > 0.20). Likewise, no beneficial effects of DHEA substitution could be observed in any of the other tests of the neuropsychological test battery in either sex (all P > 0.20). In conclusion, the present data do not support the idea of strong beneficial effects of a physiological DHEA substitution on well-being or cognitive performance in healthy elderly individuals.

Sex differences in endocrine and psychological responses to psychosocial stress in healthy elderly subjects and the impact of a 2-week dehydroepiandrosterone treatment.

Evidence from animal as well as human studies has suggested that significant sex differences exist in hypothalamus-pituitary-adrenal axis (HPA) activity. As gonadal steroids could be important modulators of HPA sex differences, stress responses were investigated in subjects of advanced age after dehydroepiandrosterone (DHEA) or placebo treatment. After a 2-week treatment with 50 mg DHEA daily or placebo, 75 men and women (mean age, 67.6 yr) were exposed to the Trier Social Stress Test (TSST). The TSST is a brief psychosocial stress that consists of a free speech and mental arithmetic task in front of an audience. The results show that the TSST induced significant increases in ACTH, salivary free cortisol, total plasma cortisol, norepinephrine, and heart rates (all P < 0.0001) as well as decreased positive affect in the elderly (P = 0.0009). Men showed larger stress responses in ACTH (P = 0.004), salivary free cortisol (P = 0.044), and plasma total cortisol (P = 0.076) compared to women. No sex differences were observed in norepinephrine, epinephrine, or heart rate responses. In contrast to ACTH and cortisol response differences, women reported that they were significantly more stressed by the TSST than men (P = 0.0051). Women treated with DHEA showed ACTH stress responses similar to those of men, but significantly enhanced compared to those of women taking placebos (P < 0.009). No other stress response differences emerged between DHEA and placebo groups. Finally, DHEA treatment did not result in an improvement of subjective well-being. We conclude that elderly men show larger HPA responses than women to psychosocial stress, as studied in the TSST. Estrogen effects on hypothalamic CRF-producing neurons might be responsible for these sex differences.

Testosterone and cognition in elderly men: a single testosterone injection blocks the practice effect in verbal fluency, but has no effect on spatial or verbal memory.

BACKGROUND: The relevance of the age-associated decline in testosterone for cognition in elderly men is still poorly understood. One hypothesis is that testosterone enhances spatial abilities, while it might impair verbal skills. METHODS: Thirty elderly men received a single testosterone (250 mg testosterone enanthate) or placebo injection. Cognitive performance was tested before and 5 days after treatment using spatial as well as verbal tests. RESULTS: Five days after injection, testosterone and estradiol levels were still in the supraphysiologic range. In the verbal fluency task, the placebo group, but not the testosterone group, showed a practice effect. Therefore, the testosterone group performed significantly worse than the placebo group after treatment. No effects of testosterone were observed in the other verbal and spatial tasks. CONCLUSIONS: The present finding, that testosterone blocks the practice effect in verbal fluency, partly supports the general idea that sex steroids modulate performance in tests with known gender differences. Moreover it demonstrates that these effects can occur rapidly. However, beneficial effects on spatial cognition or memory might need more time to develop and/or might only occur when a less pronounced testosterone increase is induced.

HPA axis and memory.

The hormones of the hypothalamus-pituitary-adrenal (HPA) axis influence memory in situations of acute and chronic stress. The present review tries to summarize the current state of knowledge by describing the enhancing as well as the impairing effects of stress or glucocorticoid (GC) treatment documented in animals and humans. GCs secreted during the acquisition of a stressful task facilitate consolidation. However, acute stress (or GC treatment) unrelated to the task impairs performance. The effects of acute stress are additionally modulated by gender, age and the emotional valence of the learning material. Chronic stress in rodents has mostly impairing effects on memory and hippocampal integrity. However, other regions of the brain, such as the prefrontal cortex, are also sensitive to stress. In humans, similar observations have been reported in several patient populations as well as in older subjects. The potential to reverse these effects using behavioural or pharmacological approaches needs to be explored.

The relationship between stress induced cortisol levels and memory differs between men and women.

Epidemiological as well as experimental studies in elderly subjects have suggested that postmenopausal women are more susceptible to the memory impairing effects of elevated cortisol levels than elderly men. Little is known however about gender differences in the susceptibility to acute stress in young subjects. In the present study a total of 58 healthy young subjects learned a word list, with recall being tested after a brief distraction task. Twenty-two subjects had to learn the list after exposure to a psychosocial stressor (Trier Social Stress Test: TSST), while the remaining subjects served as controls. Free cortisol was determined via saliva samples taken before and 10 minutes after stress. Subjects exposed to the stressor, did not show impaired memory performance per se when compared to the control group. However the cortisol increase in response to the stressor was negatively correlated (r=-0.43, P<0.05) with the memory performance within the stressed group (i.e., subjects showing a larger cortisol response recalling less words than subjects showing only a small cortisol increase). Additional analysis revealed, that this correlation was solely caused by the strong association observed in men (r=-0.82, P<0.05), while no association was observed in women (r=-0.05, P=ns). Our data suggests, that gender modulates the association between cortisol and memory after stress. Whether these differences reflect activational effects of sex steroids or developmentally-programmed sex differences awaits to be determined.

Two weeks of transdermal estradiol treatment in postmenopausal elderly women and its effect on memory and mood: verbal memory changes are associated with the treatment induced estradiol levels.

The present randomized double blind study investigated the effects of a 2 week transdermal estradiol treatment on memory performance in 38 healthy elderly women. Cognitive performance was tested at baseline and after 2 weeks of estradiol or placebo treatment using verbal, semantic, and spatial memory tests as well as a mental rotation task and the Stroop. Initial results showed no differences after treatment between placebo or estradiol treated subjects. However, within treatment group analysis revealed that estradiol treated subjects who reached higher estradiol levels (larger than 29 pg/ml) performed significantly better after treatment in the delayed recall of the paired associate test (verbal memory) than subjects who reached lower estradiol levels (P < 0.05). A nonsignificant trend was observed for the immediate recall condition (P < 0.10). These findings were strengthened by correlations between treatment-induced estradiol levels and changes in verbal memory performance. In addition, there was an association between estradiol levels and mood changes. However mood changes were not significantly associated with changes in verbal memory performance (P > 0.20). The present study supports the idea that estradiol replacement has specific effects on verbal memory in healthy postmenopausal women, with delayed recall being more affected. It suggests that these effects can occur relatively rapidly, and that there may be a dose response relationship of estradiol to memory enhancement. Furthermore, the fact that these results were obtained in women who had been menopausal for an average of 17 years before entering the study indicates that the brain maintains a sensitivity for estrogens even after years of low estradiol plasma concentrations.

Opposing effects of DHEA replacement in elderly subjects on declarative memory and attention after exposure to a laboratory stressor.

Aging is accompanied by a continuous decline of the adrenal steroid hormone DHEA and its ester DHEAS. Results from studies in rodents have demonstrated that DHEA(S) administration can enhance memory in several test paradigms. However studies from this laboratory did not find positive effects of DHEA treatment on cognitive performance in young and elderly humans. With respect to a possible mechanism of DHEA activity, effects on several neurotransmitter receptors as well as a possible antiglucocorticoid action are discussed. For high levels of glucocorticoids, a disruptive effect on hippocampal mediated memory is documented in rodents and humans. Therefore it was speculated that, if an antiglucocorticoid action of DHEA would underlie the observed beneficial effects of DHEA on memory, these effects might only be detectable if subjects are stressed (and therefore have high cortisol levels). To test this hypothesis 75 elderly women and men participated in a placebo controlled experiment. Subjects took DHEA (50 mg/day) or placebo for 2 weeks (double blind). Thereafter they participated in a standardized psychosocial laboratory stressor (Trier Social Stress Test; TSST). Before and after stress exposure subjects completed two declarative memory tests (visual-verbal and spatial) as well as one attention test. In addition recall of visual material learned before stress was assessed after stress. Baseline DHEAS levels were significantly lower compared with young adults. DHEA replacement increased DHEAS levels into ranges found in young subjects. DHEA-substituted subjects showed a trend towards a larger cortisol stress response. In the visual memory test subjects under DHEA recalled less items after stress which they had learned before stress. In the attention test however subjects under DHEA performed better than subjects from the placebo group after stress. No interaction between stress and DHEA was found for the spatial memory task. The effects of DHEA substitution on memory and attention after stress exposure seem to be heterogenous. While recall of previously learned material seems to be impaired, attention is enhanced. These results do not support the idea of a direct antiglucocorticoid or anti-stress effect of DHEA on hippocampal mediated memory functions.