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Distinct stages of the menstrual cycle and the intake of oral contraceptives (OC) affect sex hormone levels, stress responses, and memory processes critically involved in the pathogenesis of mental disorders. To characterize the interaction of sex and stress hormones on memory encoding, 30 men, 30 women in the early follicular phase of the menstrual cycle (FO), 30 women in the luteal phase (LU), and 30 OC women were exposed to either a stress (socially evaluated cold-pressor test) or a control condition prior to memory encoding and immediate recall of neutral, positive, and negative words. On the next day, delayed free and cued recall was tested. Sex hormone levels verified distinct estradiol, progesterone, and testosterone levels between groups. Stress increased blood pressure, cortisol concentrations, and ratings of stress appraisal in all four groups as well as cued recall performance of negative words in men. Stress exposure in OC women led to a blunted cortisol response and rather enhanced cued recall of neutral words. Thus, pre-encoding stress facilitated emotional cued recall performance in men only, but not women with different sex hormone statuses pointing to the pivotal role of circulating sex hormones in modulation of learning and memory processes.

Reconsolidation is a post-retrieval process of restabilization of the memory trace. Previous findings from our group suggest that cortisol, a glucocorticoid hormone secreted in response to stress, enhances the reconsolidation of fear memories in healthy men. Cortisol effect was found to be very specific, enhancing only the fear memory that was reactivated (i.e. retrieved), but not the non-reactivated memory. In the current study we aimed to investigate the effects of psychosocial stress, a more ecologically valid intervention, on fear memory reconsolidation in men. Using a similar design, we expected stress induction to have comparable effects to those of cortisol intake. During the three testing days, the participants went through (1) fear acquisition, (2) stress induction and memory reactivation (or the corresponding control conditions), (3) fear extinction, reinstatement and reinstatement test. Salivary cortisol, blood pressure measures and subjective ratings confirmed the success of the stress induction. Skin conductance response, serving as a measure of conditioned fear, confirmed acquisition, fear retrieval, and extinction in all groups. In the three control groups (where either reactivation, stress, or both components were missing) reinstatement effects were seen as expected. Yet in contrast to the hypothesis, the target group (i.e. combining reactivation and stress) showed no reinstatement to any of the stimuli. Stress induction is thus suggested to have a general impairing effect on the reconsolidation of fear memories. The unique characteristic of the stress response and experience compared to a pharmacological intervention are proposed as possible explanations to the findings. This disruptive effect of stress on fear memory reconsolidation may have potential therapeutic implications.

Stress exposure causes a structural reorganization in neurons of the amygdala. In particular, animal models have repeatedly shown that both acute and chronic stress induce neuronal hypertrophy and volumetric increase in the lateral and basolateral nuclei of amygdala. These effects are visible on the behavioral level, where stress enhances anxiety behaviors and provokes greater fear learning. We assessed stress and anxiety levels in a group of 18 healthy human trauma-exposed individuals (TR group) compared to 18 non-exposed matched controls (HC group), and related these measurements to amygdala volume. Traumas included unexpected adverse experiences such as vehicle accidents or sudden loss of a loved one. As a measure of aversive learning, we implemented a cued fear conditioning paradigm. Additionally, to provide a biological marker of chronic stress, we measured the sensitivity of the hypothalamus-pituitary-adrenal (HPA) axis using a dexamethasone suppression test. Compared to the HC, the TR group showed significantly higher levels of chronic stress, current stress and trait anxiety, as well as increased volume of the left amygdala. Specifically, we observed a focal enlargement in its lateral portion, in line with previous animal data. Compared to HC, the TR group also showed enhanced late acquisition of conditioned fear and deficient extinction learning, as well as salivary cortisol hypo-suppression to dexamethasone. Left amygdala volumes positively correlated with suppressed morning salivary cortisol. Our results indicate differences in trauma-exposed individuals which resemble those previously reported in animals exposed to stress and in patients with post-traumatic stress disorder and depression. These data provide new insights into the mechanisms through which traumatic stress might prompt vulnerability for psychopathology.

Stress affects memory beyond hippocampus-dependent spatial or episodic memory processes. In particular, stress may influence also striatum-dependent stimulus-response (S-R) memory processes. Rodent studies point to an important role of glucocorticoids in the modulation of S-R memory. However, whether glucocorticoids influence S-R memory processes in humans is still unknown. Therefore, we examined in the current experiment the impact of glucocorticoids on the formation of S-R memories in humans. For this purpose, healthy men and women received either hydrocortisone or a placebo 45 min before completing an S-R association learning task and an S-R navigation task. In addition, participants performed also a virtual spatial navigation task and a spatial navigation task in a real environment. Memory of all four learning tasks was tested one week later. Our data showed that hydrocortisone before learning enhanced memory of the S-R association learning task. Moreover, hydrocortisone enhanced the memory of the virtual spatial navigation task, mainly in women. Memory performance in the other tasks remained unaffected by hydrocortisone. These findings provide first evidence that glucocorticoids may facilitate S-R memory formation processes in humans.

Acute psychosocial stress activates the physiological and endocrine stress systems and increases the subjective emotional experience of stress. While considerable efforts have been made to link changes in the activity of the biological stress systems with changes in the subjective emotional experience of stress, results so far have been mixed, at best. To investigate this association in a study employing experimental manipulation, we pharmacologically suppressed both the autonomic and the endocrine stress responses, and investigated the effects of acute psychosocial stress on the emotional stress experience. 22 healthy men and women received dexamethasone (2 mg) the day before, and propranolol (80 mg) one hour before psychosocial stress induction. A control group (n = 24) received placebo pills on each occasion. Salivary cortisol, alpha-amylase and heart-rate responses to stress were assessed before, during and after stress induction. Subjective stress, mood, and state self-esteem assessments were made before and after stress. In the pharmacological manipulation group, subjects demonstrated no increase in autonomic or endocrine stress response, after exposure to psychosocial stress. Despite these effects, the emotional stress experience was intact in this group and identical to the control group. Participants in the experimental group showed an increase in subjective stress, greater mood dysregulation, and lower state self-esteem following stress exposure, with the response magnitude comparable to the control group. Our findings suggest that at least acutely, the physiological stress arousal systems and the emotional experience of stress are dissociated. This raises important questions about the efficacy of our measurement of subjective stress, and the unique contributions of the autonomic and endocrine responses in the subjective stress experience.

Although stress is well known to modulate human memory, precisely how memory formation is altered by a stressful encounter remains unclear. Stress effects on cognition are mainly mediated by the rapidly acting sympathetic nervous system, resulting in the release of catecholamines, and the slower acting hypothalamus-pituitary-adrenal axis secreting cortisol, which induces its effects on cognition through fast, non-genomic actions and delayed, genomic actions. Importantly, these different waves of the physiological stress response are thought to dynamically alter neural processing in brain regions important for memory such as the amygdala and the hippocampus. However, the precise time course of stress effects on memory formation is still unclear. To track the development of stress effects on memory over time, we tested individuals who underwent a stressful experience or a control procedure before a 2-h walk through a zoo, while an automatic camera continuously photographed the events they encoded. In a recognition memory test one week later, participants were presented with target photographs of their own zoo tour and lure photographs from an alternate tour. Stressed participants showed better memory for the experimental treatment than control participants, and this memory enhancement for the stressful encounter itself was directly linked to the sympathetic stress response. Moreover, stress enhanced memory for events encoded 41-65min after stressor onset, which was associated with the cortisol stress response, most likely arising from non-genomic cortisol actions. However, memory for events encoded long after the stressor, when genomic cortisol actions had most likely developed, remained unchanged. Our findings provide novel insights into how stress effects on memory formation develop over time, depending on the activity of major physiological stress response systems.

Summary Background One of the most widely studied genetic polymorphisms regarding cognitive and emotional phenotypes is the COMT Val158Met polymorphism that influences dopamine availability in the prefrontal cortex (PFC). The PFC is the key brain structure for higher cognitive functions such as working memory, as well as an important regulatory site and target of the psychoendocrine stress response. Dopamine is thought to influence PFC functions in an inverted u-shaped manner. Thus, a stress-related increase in prefrontal dopamine is hypothesized to exert differential effects on working memory performance depending on the genetically determined baseline dopamine level in the PFC. Method Thirty-three healthy young subjects homozygous for the COMT Val158Met polymorphism were selected from a larger pre-genotyped sample. They performed an n-back working memory task after exposure to a laboratory psychosocial stress induction paradigm (The Trier Social Stress Test for Groups; TSST-G). Results Under stress, working memory performance of Met homozygotes was significantly worse than working memory performance of Val homozygotes. Importantly, this genotype effect was restricted to the medium difficulty level of the n-back task. Conclusion Our results demonstrate that working memory performance under stress is influenced by genetic variation in prefrontal dopamine levels. More generally, our results point to the importance of considering the complex interaction of genes, environment, and task variables.

Summary Previous evidence indicates that stress hormone effects on memory consolidation depend on concurrent emotional arousal-induced noradrenergic activity. Here, we asked whether this is also true for stress effects on memory retrieval and hypothesized that administration of the β-adrenoceptor antagonist propranolol would block the effects of stress on declarative and procedural retrieval performance. In a double-blind, placebo-controlled, crossover study, 44 healthy young men learned a list of emotional and neutral words (declarative memory task) and completed a serial reaction time task (procedural memory task). On the following day, participants received either a placebo or 40 mg propranolol orally. One hour later, they were exposed to stress (socially evaluated cold pressor test (SECPT)) or a control condition 30 min prior to retention testing. Stress selectively enhanced the retrieval of emotionally arousing words. Pretreatment with propranolol had no effect on memory alone but blocked the stress-induced memory enhancement for emotional words, confirming the importance of noradrenergic activity in stress effects on memory retrieval. Memory for neutral words and the procedural task was neither affected by stress nor by propranolol. The present findings suggest that stress (hormone) effects on emotional memory retrieval require concurrent noradrenergic activation. Procedural memory retrieval and the retrieval of neutral verbal material appear to be less susceptible to stress.

In contrast to the substantial number of studies investigating the effects of stress on declarative memory, effects of stress on working memory have received less attention. We compared working memory (numerical n-back task with single digits) in 40 men exposed either to psychosocial stress (Trier Social Stress Test (TSST)) or a control condition. Task difficulty was varied using two conditions (2-back vs. 3-back). 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) were assessed immediately before and three times after the stress or control condition. As expected stress resulted in an increase in cortisol, sAA, and negative affect. Subjects exposed to stress showed significant working memory impairments in both workload conditions. The analysis of variance indicated a main effect of stress for reaction time as well as accuracy. In addition, for reaction time a stress-block interaction occurred. Follow up tests revealed that only during the first block at each level of difficulty performance was significantly impaired by stress. Thus, the effects of stress became smaller the longer the task was performed. Results provide further evidence for impaired working memory after acute stress and illustrate the time course of this phenomenon.

Ample research demonstrates that pathophysiological levels of the pro-inflammatory cytokine interleukin-1 (IL-1) produces detrimental effects on memory functioning. However, recent evidence suggests that IL-1 may be required for the normal physiological regulation of hippocampal-dependent memory. To substantiate the physiological role of IL-1 in learning and memory we examined the induction of IL-1 gene expression following a learning experience, and the effects of IL-1 signaling blockade, by either genetic or pharmacological manipulations, on memory functioning. We show that IL-1 gene expression is induced in the hippocampus 24h following fear-conditioning in wild type mice, but not in two mouse strains with impaired IL-1 signaling. Moreover, we report that mice with transgenic over-expression of IL-1 receptor antagonist restricted to the CNS (IL-1raTG) display impaired hippocampal-dependent and intact hippocampal-independent memory in the water maze and fear-conditioning paradigms. We further demonstrate that continuous administration of IL-1ra via osmotic minipumps during prenatal development disrupt memory performance in adult mice, suggesting that IL-1 plays a critical role not only in the formation of hippocampal-dependent memory but also in normal hippocampal development. Finally, we tested the dual role of IL-1 in memory by intracerebroventricular (ICV) administration of different doses of IL-1beta and IL-1ra following learning, providing the first systematic evidence that the involvement of IL-1 in hippocampal-dependent memory follows an inverted U-shaped pattern, i.e., a slight increase in brain IL-1 levels can improve memory, whereas any deviation from the physiological range, either by excess elevation in IL-1 levels or by blockade of IL-1 signaling, results in impaired memory.

The hormone cortisol is often believed to play a pivotal role in the effects of stress on human cognition. This meta-analysis is an attempt to determine the effects of acute cortisol administration on core executive functions. Drawing on both rodent and stress literatures, we hypothesized that acute cortisol administration would impair working memory and set-shifting but enhance inhibition. Additionally, because cortisol is thought to exert different nongenomic (rapid) and genomic (slow) effects, we further hypothesized that the effects of cortisol would differ as a function of the delay between cortisol administration and cognitive testing. Although the overall analyses were nonsignificant, after separating the rapid, nongenomic effects of cortisol from the slower, genomic effects of cortisol, the rapid effects of cortisol enhanced response inhibition, g+ = 0.113, p=.016, but impaired working memory, g+ = -0.315, p=.008, although these effects reversed over time. Contrary to our hypotheses, there was no effect of cortisol administration on set-shifting. Thus, although we did not find support for the idea that increases in cortisol influence set-shifting, we found that acute increases in cortisol exert differential effects on working memory and inhibition over time.

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.

According to recent studies, elevated cortisol levels are associated with impaired declarative memory performance. This specific effect of cortisol has been shown in several studies using pharmacological doses of cortisol. The present study was designed to determine the effects of endogenously stimulated cortisol secretion on memory performance in healthy middle-aged women. For psychological stress challenging, we employed the Trier Social Stress Test (TSST). Subjects were assigned to either the TSST or a non-stressful control condition. Declarative and non-declarative memory performance was measured by a combined priming-free-recall-task. No significant group differences were found for memory performance. Post hoc analyses of variance indicated that regardless of experimental condition the subjects with remarkably high cortisol increase in response to the experimental procedure (high responders) showed increased memory performance in the declarative task compared to subjects with low cortisol response (low responders). The results suggest that stress-induced cortisol failed to impair memory performance. The results are discussed with respect to gender-specific effects and modulatory effects of the sympathetic nervous system and psychological variables.

Clarifying the mechanisms that underlie stress-induced alterations of learning and memory may lend important insight into susceptibility factors governing the development of stress-related psychological disorders, such as post-traumatic stress disorder (PTSD). Previous work has shown that carriers of the ADRA2B Glu(301)-Glu(303) deletion variant exhibit enhanced emotional memory, greater amygdala responses to emotional stimuli and greater intrusiveness of traumatic memories. We speculated that carriers of this deletion variant might also be more vulnerable to stress-induced enhancements of long-term memory, which would implicate the variant as a possible susceptibility factor for traumatic memory formation. One hundred and twenty participants (72 males, 48 females) submerged their hand in ice cold (stress) or warm (no stress) water for 3min. Immediately afterwards, they studied a list of 42 words varying in emotional valence and arousal and then completed an immediate free recall test. Twenty-four hours later, participants' memory for the word list was examined via free recall and recognition assessments. Stressed participants exhibiting greater heart rate responses to the stressor had enhanced recall on the 24-h assessment. Importantly, this enhancement was independent of the emotional nature of the learned information. In contrast to previous work, we did not observe a general enhancement of memory for emotional information in ADRA2B deletion carriers. However, stressed female ADRA2B deletion carriers, particularly those exhibiting greater heart rate responses to the stressor, did demonstrate greater recognition memory than all other groups. Collectively, these findings implicate autonomic mechanisms in the pre-learning stress-induced enhancement of long-term memory and suggest that the ADRA2B deletion variant may selectively predict stress effects on memory in females. Such findings lend important insight into the physiological mechanisms underlying stress effects on learning and their sex-dependent nature.

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, P0.05) 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, P0.05), 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.

This paper summarizes recent findings on the amygdala’s role in mediating acute effects of glucocorticoids on memory consolidation in rats. Posttraining activation of glucocorticoidsensitive pathways involving glucocorticoid receptors (GRs or type II) enhances memory consolidation in a dose-dependent inverted-U fashion. Selective lesions of the basolateral nucleus of the amygdala (BLA) or infusions of b-adrenoceptor antagonists into the BLA block the memory-modulatory effects of systemic injections of glucocorticoids. Additionally, posttraining infusions of a specific GR agonist administered directly into the BLA enhance memory consolidation, whereas those of a GR antagonist impair. These findings indicate that glucocorticoid effects on memory consolidation are mediated, in part, by an activation of GRs in the BLA and that the effects require b-adrenergic activity in the BLA. Other findings indicate that the BLA interacts with the hippocampus in mediating glucocorticoidinduced modulatory influences on memory consolidation. Lesions of the BLA or inactivation of b-adrenoceptors within the BLA also block the memory-modulatory effects of intrahippocampal administration of a GR agonist or antagonist. These findings are in agreement with the general hypothesis that the BLA integrates hormonal and neuromodulatory influences on memory consolidation. However, the BLA is not a permanent locus of storage for this information, but modulates consolidation processes for explicit:associative memories in other brain regions, including the hippocampus. © 2000 Elsevier Science Ltd. All rights reserved.

Oxytocin receptors in several regions of the limbic system are regulated by gonadal steroids and play an important role in the mediation of maternal, sexual and affiliative behaviors. We have previously reported oxytocin receptor regulation by glucocorticoids in hippocampus and subiculum-neuroanatomical regions implicated in memory and stress regulation. In the current study we examined oxytocin receptor regulation by stress and high glucocorticoid concentration in adrenally intact male rats. Single prolonged stress and chronic non-habituating stress were used as experimental conditions in the first study, and chronic non-habituating and high dose corticosterone implants in the second. Oxytocin receptor concentration was assessed using in vitro receptor autoradiography with [125I]OVTA at the approximate KD concentration. Both stress paradigms increased oxytocin receptor binding (F = 3.7, df = 2, p = .03) across brain regions in the first study. Chronic non-habituating stress and corticosterone implants increased oxytocin receptor binding in the ventral hippocampus only (one-way ANOVA, F = 3.88, df = 2, p < .05). The current studies demonstrate that stress increases oxytocin receptor binding in areas of the CNS that are rich in glucocorticoid receptors, such as hippocampus. This suggests differential regulation of oxytocin receptors in CNS, depending upon their functional role in different regions. Oxytocin receptor modulation could mediate some of the long-term effects of stress on memory, and possibly play a role in the regulation of hypothalamo-pituitary-adrenal stress response. The ability of circulating glucocorticoids to up-regulate these receptors suggests a plausible mechanism for this stress-sensitive regulation.

Stress can exert profound effects on memory encoding. Here, we investigated whether (sub)cortical information processing during encoding and memory retrieval at a 24 h delayed test are affected by the temporal proximity between stress and memory encoding. Sixty-four participants engaged in the Maastricht Acute Stress Test (MAST) or a no-stress control condition either immediately before (i.e., proximate condition) or 30 min before (i.e., distant condition) a picture encoding task. In general, stress decreased the number of freely recalled and recognized pictures and increased the number of false alarms. However, timing of stress exposure did not differentially affect picture recall, recognition or selective attention processes (i.e., LPP). Nevertheless, stress-induced cortisol responses and correctly recognized neutral pictures were positively associated within the proximate stress condition but negatively associated within the distant stress condition. These findings suggest that the time at which a stressor is applied might differentially impact the association between stress-induced cortisol elevations and memory formation and indicate the need for a finer delineation of the time window during which glucocorticoids affect memory formation processes.

Summary Stress effects on memory are well-known. Most studies, however, focused on the impact of stress on hippocampus-dependent ‘declarative’ memory processes. Less is known about whether stress influences also striatum-based memory processes, such as stimulus–response (S–R) memory. First evidence from rodent experiments shows that glucocorticoid stress hormones may enhance the consolidation of S–R memories. Whether stress affects also S–R memory retrieval remains largely elusive. Therefore, we tested in the present experiment in humans the effect of stress on the retrieval of S–R memories. Healthy men and women were trained to locate three objects in an S–R version of a virtual eight-arm radial maze. One week later, participants underwent a stressor or a control condition before their memory of the S–R task was tested. Our results showed that participants ( n = 43) who were exposed to the stressor before retention testing made significantly more errors in this test trial, suggesting that stress impaired S–R memory retrieval. Moreover, high cortisol concentrations were associated with reduced S–R memory. These findings indicate that stress may affect memory retrieval processes in humans beyond hippocampal ‘declarative’ memory.

Glucocorticoids, stress hormones released from the adrenal cortex, are important players in the regulation of emotional memory. Specifically, in animals and in humans, glucocorticoids enhance memory consolidation of emotionally arousing experiences, but impair memory retrieval. These glucocorticoid actions are partly mediated by glucocorticoid receptors in the hippocampus, amygdala and prefrontal cortex, key brain regions for emotional memory. In a recent study in patients who underwent cardiac surgery, the BclI polymorphism of the glucocorticoid receptor gene (NR3C1) was associated with traumatic memories and posttraumatic stress disorder symptoms after intensive care therapy. Based on this finding, we investigated if the BclI polymorphism is also associated with emotional memory in healthy young subjects (N=841). We used a picture-learning task consisting of learning and recalling neutral and emotional photographs on two consecutive days. The BclI variant was associated with short-delay recall of emotional pictures on both days, with GG carriers showing increased emotional memory performance as compared to GC and CC carriers. We did not detect a genotype-dependent difference in recall performance for neutral pictures. These findings suggest that the Bcll polymorphism contributes to inter-individual differences in emotional memory also in healthy humans.

It is well established that stress and glucocorticoids can affect memory. Psychosocial stress has been reported to eliminate retrieval-induced forgetting (RIF), the phenomenon that repeated retrieval of a subset of previously learned material impairs later recall of related, but non-retrieved information. The stress-related reduction of RIF has been found correlated with an increase in salivary cortisol levels. Based on these findings, the current placebo-controlled study examined the effect of an oral dose of 25 mg hydrocortisone on the RIF effect in 37 healthy men. Even though participants in the hydrocortisone group showed a marked increase in salivary cortisol, retrieval-induced forgetting was not affected by the pharmacological treatment. Thus, cortisol administration alone in contrast to stress experience does not impair the RIF effect. However, participants with high state anxiety during retrieval practice did not show RIF, whereas participants with low state anxiety did. This finding suggests a role for state anxiety in stress-related elimination of retrieval-induced forgetting, perhaps indicative of a memory-modulating sympathetic nervous system effect. (C) 2012 Elsevier Ltd. All rights reserved.

Summary Background In the present study, we aimed to compare the effect of exogenous cortisol on memory retrieval in posttraumatic stress disorder (PTSD) with the effects in healthy controls. In healthy participants, administration of cortisol impairs declarative memory retrieval. Only a few studies have investigated these effects in PTSD yielding mixed results. Methods In a placebo-controlled crossover study, 44 patients with PTSD and 65 healthy controls received either placebo or 10 mg of hydrocortisone orally before memory testing. In addition to declarative memory retrieval (word list learning), we also tested autobiographical memory retrieval specificity. Results In both tasks opposing effects of cortisol on memory were observed when comparing patients with controls. In controls, cortisol had impairing effects on memory retrieval, while in PTSD patients cortisol had enhancing effects on memory retrieval in both memory domains. Conclusions The present results suggest beneficial effects of acute cortisol elevations on hippocampal mediated memory processes in PTSD. Possible neurobiological mechanisms underlying these findings are discussed.

It is widely recognized that acute stress and associated glucocorticoid stress responses yield memory-enhancing effects when the memory consolidation phase is targeted, while impairing effects are generally found with regard to memory retrieval performance. While some evidence exists that the memory-enhancing effects of consolidation stress are modulated by time of day, no study to date has investigated whether stress-induced retrieval deficits are also prone to such time of day effects. To address this issue, participants (N = 76) were exposed to a stressor or control condition before a retrieval test that probed for neutral and negative words learned 24 h before. Results show that stress exposure resulted in impaired retrieval of both neutral and negative words, but that time of day did not moderate this effect. This memory-impairing effect was larger for negative than for neutral information, and was significantly associated with stress-induced cortisol responses. The current findings demonstrate the robustness of stress-induced retrieval deficits throughout the day, in particular for emotional memory material, and further underscore the importance of cortisol reactivity in impairing memory retrieval. (PsycINFO Database Record (c) 2011 APA, all rights reserved) (journal abstract)

High levels of cortisol, a sign of potential hypothalamic-pituitary-adrenal (HPA) axis dysregulation, have been associated with poor cognitive outcomes in older adults. Most cortisol research has focused on hippocampal-related abilities such as episodic memory; however, the presence of glucocorticoid receptors in the human prefrontal cortex suggests that cortisol regulation is likely to be associated with prefrontally-mediated executive function abilities. We hypothesized that elevated cortisol levels would be associated with poorer frontal-executive function in addition to episodic memory. We assessed cortisol from 15 saliva samples paralleling individual diurnal rhythms across three non-consecutive days in a group of 778 middle-aged twin men ages 51 to 60. Cognitive domains created from 24 standard measures included: general cognitive ability, verbal and visual-spatial ability, verbal and visual-spatial memory, short-term/immediate memory, working memory, executive function, verbal fluency, abstract reasoning, and psychomotor processing speed. Adjusting for general cognitive ability at age 20, age, race, and multiple health and lifestyle indicators, higher levels of average area-under-the-curve cortisol output across three days were significantly associated with poorer performance in three domains: executive (primarily set-shifting) measures, processing speed, and visual-spatial memory. In a 35-year longitudinal component of the study, we also found that general cognitive ability at age 20 was a significant predictor of midlife cortisol levels. These results possibly support the notion that glucocorticoid exposure is associated with cognitive functions that are mediated by frontal-striatal systems, and is not specific to hippocampal-dependent memory. The results also suggest that the direction of effect is complex.

Previous experimental studies in humans have reported that the administration of cortisol impairs retrieval of hippocampal dependent, episodic memory. In particular, cortisol impaired recall of previously learnt words. In the present study, we investigated if cortisol also affects autobiographical memory, which reflects a subcategory of hippocampal dependent, episodic memory. Twenty two male students participated in this placebo-controlled, double-blind crossover study. One hour after the administration of 10 mg hydrocortisone, subjects generated significantly fewer specific memories in the Autobiographical Memory Test (AMT) when compared to placebo. In contrast, cortisol did not affect mood and attention. The present findings extend the current knowledge about cortisol effects on memory retrieval and raise the possibility that impaired autobiographical memory in depression may be at least partly due to elevated cortisol levels which often accompany this disorder.

Memory tends to be better for emotionally arousing information than for neutral information. Evidence from animal studies indicates that corticosteroids may be necessary for this memory enhancement to occur. We extend these findings to human memory performance. Following administration of cortisol (20 mg) or placebo, participants were exposed to pictures varying in emotional arousal. Incidental memory for the pictures was assessed one week later. We show that elevated cortisol levels during memory encoding enhances the long-term recall performance of emotionally arousing pictures relative to neutral pictures. These results extend previous work on corticosteroid enhancement of memory and suggest that high cortisol levels during arousing events result in enhanced memory in humans.