Stress-induced Increases In Cortisol Research Articles

11β-Hydroxysteroid dehydrogenase type 2 may mediate the stress-specific effects of cortisol on brain cell proliferation in adult zebrafish (Danio rerio).

Stress-induced increases in cortisol can stimulate or inhibit brain cell proliferation, but the mechanisms behind these opposing effects are unknown. We tested the hypothesis that 11β-hydroxysteroid dehydrogenase type 2 (Hsd11b2), a glucocorticoid-inactivating enzyme expressed in neurogenic regions of the adult zebrafish brain, mitigates cortisol-induced changes to brain cell proliferation, using one of three stress regimes: a single 1min air exposure (acute stress), two air exposures spaced 24 h apart (repeat acute stress) or social subordination (chronic stress). Plasma cortisol was significantly elevated 15 min after air exposure and recovered within 24 h after acute and repeat acute stress, whereas subordinate fish exhibited significant and sustained elevations relative to dominant fish for 24 h. Following acute stress, brain hsd11b2 transcript abundance was elevated up to 6 h after a single air exposure but was unchanged by repeat acute stress or social subordination. A sustained increase in brain Hsd11b2 protein levels occurred after acute stress, but not after repeat or chronic stress. Following acute and repeat acute stress, brain pcna transcript abundance (a marker of cell proliferation) exhibited a prolonged elevation, but was unaffected by social subordination. Interestingly, the number of telencephalic BrdU+ cells increased in fish after a single air exposure but was unchanged by repeat acute stress. Following acute and repeat acute stress, fish expressed lower brain glucocorticoid and mineralocorticoid receptor (gr and mr) transcript abundance while subordinate fish exhibited no changes. Taken together, these results demonstrate stressor-specific regulation of Hsd11b2 in the zebrafish brain that could modulate rates of cortisol catabolism contributing to observed differences in brain cell proliferation.

Stress affects the prediction of others' behavior.

Predicting behavior of other people is vital for successful social interactions. We tested whether a stress-induced cortisol increase affects healthy young men's prediction of another individual's behavior. Forty-two participants were randomly assigned to a stress or to a control condition. Afterwards, they participated in a modified false-belief task that not only tests false-belief understanding but also the tendency to predict another person's future behavior based on his former behavior. Subjective ratings and salivary cortisol concentrations revealed a successful stress induction. Stress did not affect participants' attribution of false beliefs but it increased the probability to predict that a protagonist would act according to his former behavior. Recognizing that stress fosters the interpretation of others' behavior following their former behavior and not their current goals extends previous research showing that stress fosters our own habitual behavior.

Adult age differences in the psychophysiological response to acute stress

Age-related differences in the psychophysiology of the acute stress response are poorly understood given the limited number of studies and the high heterogeneity of findings. The present study contributes by investigating age differences in both the psychological and physiological responses to acute stress in a sample of healthy younger (N = 50; 18–30; Mage = 23.06; SD = 2.90) and older adults (N = 50; 65–84; Mage = 71.12; SD = 5.02). Specifically, the effects of psychosocial stress (i.e., age-adapted Trier Social Stress Test) were investigated at numerous timepoints throughout the stress response phases (i.e., baseline, anticipation, reactivity, recovery) on cortisol, heart rate, subjective stress, and anticipatory appraisal of the stressful situation. The study was conducted in a between-subject (younger vs. older) cross-over (stress vs. control) design. Results revealed age-related differences in both physiological and psychological variables: older adults had overall lower salivary cortisol levels in the stress and control conditions and lower stress-induced cortisol increase (i.e., AUCi). In addition, older adults’ cortisol reactivity was delayed compared to younger adults. Older adults showed a lower heart rate response in the stress condition while no age differences were observed in the control condition. Finally, older adults reported less subjective stress and a less negative stress appraisal during the anticipation phase than younger adults, which could potentially explain lower physiological reactivity in this age group. Results are discussed in relation to the existing literature, potential underlying mechanisms, and future directions for the field.

Normalizing the Optical Signal Enables Robust Assays with Lateral Flow Biosensors.

Lateral flow assays (LFAs) are widely adopted for fast, on-site molecular diagnostics. Obtaining high-precision assay results, however, remains challenging and often requires a dedicated optical setup to control the imaging environment. Here, we describe quick light normalization exam (qLiNE) that transforms ubiquitous smartphones into a robust LFA reader. qLiNE used a reference card, printed with geometric patterns and color standards, for real-time optical calibration: a photo of an LFA test strip was taken along with the card, and the image was processed using a smartphone app to correct shape distortion, illumination brightness, and color imbalances. This approach yielded consistent optical signal, enabling quantitative molecular analyses under different illumination conditions. We adapted qLiNE to detect cortisol, a known stress hormone, in saliva samples at point-of-use settings. The assay was fast (15 min) and sensitive (detection limit, 0.16 ng/mL). The serial qLiNE assay detected diurnal cycles of cortisol levels as well as stress-induced cortisol increase.

Stress-Induced Increase in Cortisol Negatively Affects the Consolidation of Contextual Elements of Episodic Memories.

Stress can modulate episodic memory in various ways. The present study asks how post-encoding stress affects visual context memory. Participants encoded object images centrally positioned on background scenes. After encoding, they were either exposed to cold pressure stress (CPS) or a warm water control procedure. Forty-right hours later, participants were cued with object images, and for each image, they were asked to select the background scene with which it was paired during study among three highly similar options. Only male but not female participants reacted with a significant increase in salivary cortisol to CPS, and the stress and control group did not differ in recognition performance. Comparing recognition performance between stress responders and non-responders, however, revealed a significant impairment in context memory in responders. Additionally, proportional increase in cortisol was negatively correlated with the number of correctly recognized scenes in responders. Due to the small number of responders, these findings need to be interpreted with caution but provide preliminary evidence that stress-induced cortisol increase negatively affects the consolidation of contextual elements of episodic memories.

The Effect of Stress on Repeated Painful Stimuli with and Without Painful Conditioning.

Stress and pain have been interrelated in clinical widespread pain conditions. Studies indicate that acute experimental stress in healthy volunteers has a negative effect on the descending inhibitory pain control system and thus the ability to inhibit one painful stimulus with another (conditioned pain modulation [CPM]) although without effect on general pain sensitivity. CPM effects can be assessed immediately after the stress induction, whereas some physiological stress responses (e.g., cortisol release) are delayed and longer lasting. It is unclear whether CPM may relate to stress-induced increases in cortisol. Twenty-five healthy men had CPM effects measured over a period of 10 minutes. Pain detection thresholds (PDTs) were assessed by repeated test stimuli with cuff algometry on one leg, with and without painful cuff pressure conditioning on the contralateral leg. CPM effects, assessed as the increase in PDT during conditioning stimulation compared with without, were measured before and after experimental stress and a control condition (Montreal Imaging Stress Task [MIST]). Saliva cortisol levels and self-perceived stress were collected. Participants reported the MIST to be more stressful compared with the MIST control, but cortisol levels did not change significantly from baseline. In all sessions, PDT increased during conditioning (P = 0.001), although the MIST compared with the MIST control had no significant effect on PDT or CPM effects. A negative correlation between changes in cortisol and conditioned PDT was found when applying the MIST (P < 0.03). No significant effect of stress was found on CPM compared with a matched control condition. Individual changes in experimental stress and in conditioned pain sensitivity may be linked with cortisol.

The effect of stress-induced cortisol increase on the sense of ankle proprioception.

The aim of this study is to analyze the effect of stress-induced cortisol increase on the sense of ankle proprioception. Between April 2016 and May 2016, a total of 60 students (30 males, 30 females; mean age: 19.2±1.5 years; range, 19 to 20 years) from İnönü University, Faculty of Medicine, Department of Freshmen were included in the study. Separate measurements were made for the right and left ankle to make ankle proprioception measurements a month before the committee exam during their relaxed period using a device designed with digital inclinometer. The sense of ankle proprioception was measured at 10° dorsiflexion (DF), 11° plantar flexion (PF), and 25° PF angles with open eyes and closed eyes using active reproduction test. Salivary samples were taken for stress assessment and State Trait Anxiety Inventory-I (STAI-I) was conducted. The same tests were repeated on the day of committee exam. Test results showed no statistically significant difference between the right and left ankle proprioception measurements of 10° DF, 11° PF, and 25° PF angles with open eyes (p>0.05). However, a statistically significant difference was found between the right and left ankle proprioception scores at the same angles with closed eyes (p<0.05). According to the Wilcoxon analysis conducted for the comparison of the relaxed and stressed periods of cortisol and STAI-I inventory, a statistically significant difference was found (p<0.05). The Spearman's Rho analysis showed no significant correlation between the right and left ankle proprioception scores and cortisol and STAI-I with open eyes, while there was a statistically significantly positive direction and low correlation between the same angles with closed eyes. Our study results show that the increase in the stress-related cortisol is negative for the ankle proprioception sense.

Stress, Motivation, and the Gut-Brain Axis: A Focus on the Ghrelin System and Alcohol Use Disorder.

Since its discovery, the gut hormone, ghrelin, has been implicated in diverse functional roles in the central nervous system. Central and peripheral interactions between ghrelin and other hormones, including the stress-response hormone cortisol, govern complex behavioral responses to external cues and internal states. By acting at ventral tegmental area dopaminergic projections and other areas involved in reward processing, ghrelin can induce both general and directed motivation for rewards, including craving for alcohol and other alcohol-seeking behaviors. Stress-induced increases in cortisol seem to increase ghrelin in the periphery, suggesting a pathway by which ghrelin influences how stressful life events trigger motivation for rewards. However, in some states, ghrelin may be protective against the anxiogenic effects of stressors. This critical review brings together a dynamic and growing literature, that is, at times inconsistent, on the relationships between ghrelin, central reward-motivation pathways, and central and peripheral stress responses, with a special focus on its emerging role in the context of alcohol use disorder.

Association between changes in heart rate variability during the anticipation of a stressful situation and the stress-induced cortisol response

Vagal activity – reflecting the activation of stress regulatory mechanisms and prefrontal cortex activation – is thought to play an inhibitory role in the regulation of the hypothalamus–pituitary–adrenal axis. However, most studies investigating the association between stress-induced changes in heart rate variability (HRV, an index of cardiac vagal tone) and cortisol have shown a non-significant relationship. It has been proposed that physiological changes observed during anticipation of a stressor allow individuals to make behavioral, cognitive, and physiological adjustments that are necessary to deal with the upcoming actual stressor. In this study, in a large sample of 171 healthy adults (96 men and 75 women; mean age = 29.98, SD = 11.07), we investigated whether the cortisol response to a laboratory-based stress task was related to anticipation-induced or stress task-induced changes in HRV. As expected, regression analyses showed that a larger decrease in HRV during the anticipation of a stress task was related to higher stress task-induced cortisol increase, but not cortisol recovery. In line with prior research, the stress task-induced change in HRV was not significantly related to cortisol increase or recovery. Our results show for the first time that anticipatory HRV (reflecting differences in stress regulation and prefrontal activity before the encounter with the stressor) is important to understand the stress-induced cortisol increase.

The impact of acute stress on cognitive functioning: a matter of cognitive demands?

ABSTRACTIntroduction: There is a controversy in the literature whether stress and related cortisol responses are beneficial or impairing for cognitive functioning. Conflicting results might be due to individual differences in stress reactivity and cognitive load of the applied tasks.Methods: N = 48 participants underwent the Socially Evaluated Cold Pressor Test and were confronted with the Frankfurter Aufmerksamkeits-Inventar-2 (FAIR-2) which is a low-load attention task and two subscales of the Intelligenz-Struktur-Test 2000 R (I-S-T 2000R) as a high-load reasoning task before and after the stressor. Participants were post hoc divided into high (stress induced cortisol increase of ≥1.5 nmol/l) vs. low-cortisol responders.Results: Cortisol responders showed an increased attentional performance in the post-stress condition (η2 > .14). However, there were neither stress or responder main effects nor an interaction effect on reasoning abilities.Conclusions: Results of the present study show that stress related changes in cognitive performance are due to individual differences in cortisol response and the cognitive load of the performed task. Future studies will show if these results are also valid for alternative cognitive tasks and if they can be replicated in female participants.

Stress Induces a Shift Towards Striatum-Dependent Stimulus-Response Learning via the Mineralocorticoid Receptor.

Stress is assumed to cause a shift from flexible 'cognitive' memory to more rigid 'habit' memory. In the spatial memory domain, stress impairs place learning depending on the hippocampus whereas stimulus-response learning based on the striatum appears to be improved. While the neural basis of this shift is still unclear, previous evidence in rodents points towards cortisol interacting with the mineralocorticoid receptor (MR) to affect amygdala functioning. The amygdala is in turn assumed to orchestrate the stress-induced shift in memory processing. However, an integrative study testing these mechanisms in humans is lacking. Therefore, we combined functional neuroimaging of a spatial memory task, stress-induction, and administration of an MR-antagonist in a full-factorial, randomized, placebo-controlled between-subjects design in 101 healthy males. We demonstrate that stress-induced increases in cortisol lead to enhanced stimulus-response learning, accompanied by increased amygdala activity and connectivity to the striatum. Importantly, this shift was prevented by an acute administration of the MR-antagonist spironolactone. Our findings support a model in which the MR and the amygdala play an important role in the stress-induced shift towards habit memory systems, revealing a fundamental mechanism of adaptively allocating neural resources that may have implications for stress-related mental disorders.

No effects of hydrocortisone and dexamethasone on pain sensitivity in healthy individuals.

There is some evidence that stress-induced cortisol increase leads to a decrease in pain, while lowering cortisol levels enhances pain sensitivity, but no study has yet investigated both pharmacological enhancement and reduction of cortisol levels in the same individuals. Firstly, we tested in 16 healthy individuals whether the treatment with hydrocortisone and dexamethasone, respectively, results in altered pain thresholds. Secondly, we aimed to test whether hormone effects are different across the pain range by using ratings for pain stimuli with varying intensity; and thirdly, we tested whether cortisol levels influence the discrimination ability for painful stimuli. Despite substantial effects of dexamethasone and hydrocortisone administration on cortisol levels, no effect of these drugs was seen in terms of pain sensitivity (pain threshold, pain rating, pain discrimination ability), although comprehensively examined. However, in the placebo condition, a significant negative correlation between cortisol and pain thresholds was seen. Similarly, there were also strong negative associations between cortisol levels in the placebo condition and pain thresholds after drug treatment (especially after hydrocortisone). These findings suggest that short-term variations of cortisol do not influence pain sensitivity whereas, in general, high levels of cortisol are associated with increased pain sensitivity, at least for weak to moderate stimuli.

Smaller Hippocampi in Depression Due to Childhood Maltreatment

Depression has been associated with smaller hippocampi, possibly mediated by stress-induced increases in cortisol, although some studies have suggested that a small hippocampus may be a trait that predisposes to depression. These researchers used two methods to measure hippocampal size in 85 inpatients with rigorously diagnosed major depression (mean age, 37) and 85 age-matched controls without psychiatric histories. All …

A low cortisol response to acute stress is related to worse basal memory performance in older people.

Age-related memory decline has been associated with a faulty regulation of the hypothalamus-pituitary-adrenal axis (HPA-axis). The aim of this study was to investigate whether the magnitude of the stress-induced cortisol increase is related to memory performance when memory is measured in non-stressful conditions. To do so, declarative and working memory performance were measured in 31 men and 35 women between 55 and 77 years of age. On a different day, the magnitude of their cortisol response to acute psychosocial stress was measured. The relationship between the cortisol response and memory performance was U shaped: a low cortisol response to stress was related to poorer declarative and working memory performance, whereas those who did not increase their cortisol levels and those who had the largest cortisol increase had better declarative and working memory capabilities. Sex did not moderate these relationships. These results suggest that a low cortisol response to stress could reflect a defective HPA-axis response to stressors that is accompanied by poorer memory performance. Conversely, a high cortisol response seems to reflect a correct functioning of the HPA-axis and may protect against memory deficits in the later stages of human life.

Timing matters: Temporal dynamics of stress effects on memory retrieval

Stress may impair memory retrieval. This retrieval impairment has been attributed to the action of the stress hormone cortisol, which is released with a delay of several minutes after a stressful encounter. Hence, most studies tested memory retrieval 20-30min after stress, when the stress-induced cortisol increase peaks. In the present experiment, we investigated whether retrieval impairments can also be found at later intervals after stress. To this end, participants learned a list of words on day 1. Twenty-four hours later, they were first exposed to a stressor or a nonstressful control manipulation and completed a recognition test for the words either immediately thereafter, 25min later, or 90min later. Our findings showed that stress did not impair memory retrieval when memory was tested immediately after the stressor, before cortisol levels were elevated. However, retrieval performance was impaired 25min after stress, when cortisol levels peaked, as well as 90min after the stressor, when cortisol levels had already returned to baseline. The retrieval impairment 90min after stress appeared to be even stronger than the one after 25min. These findings suggest that the detrimental effects of stress on retrieval performance may last longer than is usually assumed.

Acute stress response of European sea bass Dicentrarchus labrax under blue and white light

Recent data suggest that specific light wavelength can alleviate fish acute stress response by counteracting or reducing the stress-induced cortisol increase. The European sea bass Dicentrarchus labrax, widely reared in the Mediterranean, is very sensitive to handling stress, so that typical rearing procedures during on-growing (e.g. grading) are avoided. The present study aimed at investigating whether exposure to blue (480nm) or white light (BL or WL, respectively) could alleviate European sea bass acute stress response. Fish (initial weight 130.9±0.4g) were reared (seawater recirculating system) for 63days under BL or WL and then subjected to 1 hour confinement or left undisturbed (control). Confinement of fish under BL resulted in a higher cortisol increase, no dopaminergic activation and lower brain serotonergic activity than under WL. In contrast, WL confined fish showed a lower cortisol increase coupled with higher brain serotonergic activity and increased levels of brain dopamine. Stress-induced hematocrit increase was lower when fish were confined under BL and triacylglycerides increase was only observed for WL reared fish. Differences in some parameters between unstressed BL and WL fish suggest that light wavelength had an effect on fish physiological status irrespective of stress. Although present results are not conclusive on which fish groups were more or less stressed, they do confirm that light wavelength can differentiate European sea bass response to acute stressors. Further studies to elucidate biological mechanisms of light spectrum effects will reinforce its efficacy as a tool to manipulate intensively reared fish stress response.

Autonomic and hypothalamic–pituitary–adrenal stress resilience: Impact of cardiac vagal tone

Resilience refers to the ability to cope with stressful events. Variation in the activity of the stress-responsive sympatho–adrenal–medullary and hypothalamic–pituitary–adrenal axes is particularly important for adaptive stress responses and thus may give rise to individual differences in resilience. Here, we investigated whether cardiac vagal tone and adult attachment style are related to psychophysiological stress resilience by exposing a sample of healthy young men and women ( n = 68) to a laboratory stress test while monitoring autonomic (heart rate, salivary alpha-amylase), hypothalamic–pituitary–adrenal (salivary cortisol), and psychological stress levels. Our results demonstrate that adult attachment style did not influence autonomic, hypothalamic–pituitary–adrenal, or psychological stress responses. In contrast, higher resting cardiac vagal tone was associated with stress-induced increases in cortisol. This suggests a role for sympathetic influences on heart rate regulation in hypothalamic–pituitary–adrenal stress responses, and extends previous observations of a link between vagal tone and stress resilience.

Stress impairs retrieval of socially relevant information.

Several studies have reported that stress impairs memory retrieval, even though findings are not unequivocal. Moreover, memory for socially relevant information was not previously investigated. The present study aimed to test the effects of stress on the retrieval of social memory (e.g., memory concerning names, birthdays, or biographies). In a randomized cross-over experiment, the cognitive performance of 29 subjects (15 women) was tested twice. Social memory was tested in a stress session, in which participants were exposed to a brief standardized psychosocial laboratory stressor between encoding and retrieval. Performance was compared with a stress-free control session. Stress exposure caused an increase in cortisol concentrations and changes in several mood measures. Social memory retrieval was reduced in the stress compared with the control session. An association between the cortisol stress response and poorer retrieval was significant in responders, that is, those participants displaying a cortisol rise after stress onset. Thus, similar to other forms of declarative memory, the retrieval of declarative memory for socially relevant information learned from biographical notes is impaired after acute stress exposure. This effect is linked to the stress-induced cortisol increase.

Stress and memory retrieval in women: No strong impairing effect during the luteal phase.

Stress has been shown to impair delayed memory retrieval, but so far no study has been conducted solely with naturally cycling women. In a crossover design, 36 women (all in the luteal phase) participated in two experimental conditions (stress vs. control). Delayed memory retrieval of a wordlist learned 24 hours earlier was tested after stress or control treatment. Although stressed subjects showed a strong cortisol increase following stress, no influence on memory retrieval occurred. In an additional data analysis, subjects were split up into a cortisol responder and a cortisol nonresponder group. However, again no evidence for a stress-induced retrieval impairment became apparent. Similarly, no correlation was observed between the stress-induced cortisol increase and memory. This study failed to find an influence of stress on memory retrieval in women tested in the luteal phase. The findings are in contrast to our previous results obtained with men. Evidence is discussed that the luteal phase, which is characterized by elevated gonadal steroids, is associated with reduced glucocorticoid sensitivity. This might underlie the missing impact of stress on memory.

Stress impairs acquisition of delay eyeblink conditioning in men and women

In rodents stress impairs delay as well as trace eyelid conditioning in females, but enhances it in males. The present study tested the effects of acute psychosocial stress exposure on classical delay eyeblink conditioning in healthy men and women. In a between subject design, participants were exposed to psychosocial stress using the Trier Social Stress Test (TSST) or a control condition which was followed by a delay eyeblink classical conditioning procedure. Stress exposure led to a significant increase in salivary cortisol and impaired acquisition of conditioned eyeblink responses (CRs). This was evident by a later first CR and an overall lower CR rate of the stress group. The stress-induced acquisition impairment was observed in both women and men. Subjects failing to show a stress-induced cortisol increase (cortisol non-responder) were not impaired in acquisition. Our findings indicate that acute stress, possibly via activation of the hypothalamus–pituitary–adrenal (HPA) axis, reduces the ability to acquire a simple conditioned motor response in humans.