Gonads under stress: A systematic review and meta-analysis on the effects of acute psychosocial stress on gonadal steroids secretion in humans.

Animal research has shown that the hypothalamus-pituitary-gonadal (HPG) axis is inhibited by (chronic and/or severe) stress, which can lead to impaired fertility and reproductive functioning, presumably caused by the inhibition of gonadal steroid secretion and in interactions with glucocorticoids. However, what has not been clarified is how acute psychosocial stress modulates gonadal steroid secretion in humans. Here we summarize the experimental research on the acute effects of stress on the secretion of gonadal steroids in humans. A systematic literature search revealed 21 studies (with N=881 individuals) measuring testosterone, progesterone or estradiol in response to a standardized acute laboratory stressor in healthy humans. Both our literature review and quantitative meta-analysis suggest that in humans, acute stress stimulates rather than inhibits HPG axis activity, although there is a considerable heterogeneity in the reported methods and results. Increased gonadal steroids in response to acute stress contrasts with many animal studies reporting the opposite pattern, at least regarding severe and/or chronic stressors. We discuss methodological issues and challenges for future research and hope to stimulate experimental studies within this area. A better understanding of these mechanisms is needed, and may have important implications for health and disease, as well as the modulation of various behaviors by acute stressors.

Hydrocortisone reduces altruistic punishment in healthy men.

Psychosocial stress modulates social cognition and behavior in humans. One potentially mediating factor is cortisol as part of the human endocrine stress response. With a double-blind, placebo-controlled between-subject study design, we tested possible dose-dependent effects of hydrocortisone (0 mg, 5 mg and 20 mg) in 85 healthy males. During a socio-economic decision-making task we measured trust, trustworthiness, sharing, punishment, and non-social risk behavior. Social value orientation (SVO) was also assessed. We observed significantly lower levels of punishment after hydrocortisone, especially in the 20 mg group. Drug-induced salivary cortisol correlated negatively with punishment behavior. None of the other facets of social behavior or the SVO were affected by hydrocortisone. Our results suggest that hydrocortisone reduces the propensity to punish unfair behavior. Future studies are needed to further disentangle the role played by various psychobiological mechanisms within the stress response as well as their complex interplay on social behavior and cognition.

Effects of menstrual cycle phase and ovulation on the salivary cortisol awakening response.

The cortisol awakening response (CAR) is influenced by several state and trait variables, one of which might be the menstrual cycle in women. Previous results suggested that the CAR is enhanced around ovulation, which is why it has been recommended to avoid sampling during the ovulatory phase. In two separate studies, we aimed to replicate previous findings that reported the CAR's modulation across the menstrual cycle, especially during ovulation. In Study 1, a group of 27 healthy naturally cycling women collected saliva at 0, 30, 45, and 60 min post-awakening on two days during their follicular, ovulatory, and luteal phases in a repeated measures design. In Study 2, CAR samples were collected from 30 healthy naturally cycling women on seven consecutive days around the expected ovulation. To increase reliability of CAR measurements, participants' compliance of saliva sampling times was monitored, ovarian steroids (estradiol and progesterone) were collected, and ovulation was confirmed with specific test kits. Contrary to our expectations, we detected no differences in the CAR over the menstrual cycle, and no significant association with variations in estradiol and progesterone. In addition, we excluded confounding effects such as compliance and validated the cycle phase. These results suggest that the CAR is largely robust against hormonal variations across the menstrual cycle, including the mid-cycle phase around ovulation. However, further research is needed to understand the potential ovarian steroid-induced modulation of HPA axis functioning and the menstrual cycle's effects on salivary cortisol levels in psychobiological studies.

Enhancing precision in human neuroscience.

Human neuroscience has always been pushing the boundary of what is measurable. During the last decade, concerns about statistical power and replicability - in science in general, but also specifically in human neuroscience - have fueled an extensive debate. One important insight from this discourse is the need for larger samples, which naturally increases statistical power. An alternative is to increase the precision of measurements, which is the focus of this review. This option is often overlooked, even though statistical power benefits from increasing precision as much as from increasing sample size. Nonetheless, precision has always been at the heart of good scientific practice in human neuroscience, with researchers relying on lab traditions or rules of thumb to ensure sufficient precision for their studies. In this review, we encourage a more systematic approach to precision. We start by introducing measurement precision and its importance for well-powered studies in human neuroscience. Then, determinants for precision in a range of neuroscientific methods (MRI, M/EEG, EDA, Eye-Tracking, and Endocrinology) are elaborated. We end by discussing how a more systematic evaluation of precision and the application of respective insights can lead to an increase in reproducibility in human neuroscience.

Optimal timing of oral metyrapone intake for the suppression of cold-pressor stress-induced cortisol release.

BACKGROUND: Pharmacological manipulation of cortisol levels is instrumental in elucidating mechanisms underlying acute stress effects and for distinguishing the physiological and behavioral effects of cortisol from those of the adrenergic system. Administration (oral or IV) of hydrocortisone is a direct and efficient method to elevate cortisol, and thus, frequently used in psychobiological stress research. However, lowering of cortisol (i.e. blockade of stress cortisol) requires a more sophisticated approach, such as the administration of the corticostatic compound metyrapone (MET). However, there is insufficient knowledge about the temporal dynamics of MET for the blocking of stress-induced cortisol reactivity. Thus, the present study aimed to build up an experimental protocol suitable to suppress acute behavioral stress-induced cortisol secretion by MET. METHODS: 50 healthy young men were randomly assigned to one of five treatment groups. They received 750 mg oral MET either 30 (n = 9), 45 (n = 11), or 60 (n = 10) minutes before exposure to a combined cold pressor and mental arithmetic test (stress induction), or were subjected to two different control treatments (placebo 60 min before stress (n = 10) or MET 30 min before non-stressful warm-water condition (n = 10)). Salivary cortisol concentration, hemodynamics, and subjective ratings were assessed. RESULTS: Suppression of cold stress-induced cortisol release was strongest when MET intake was scheduled 30 min prior to stress onset. Cardiovascular stress-responses and subjective ratings remained unaffected by MET. CONCLUSION: In healthy young males, 750 mg of MET efficiently block cold stress-induced cortisol release when oral administration is scheduled 30 min prior to stress onset. This finding may guide future research in improving timing of suppression of stress-induced cortisol secretion.

The Forward Testing Effect Is Resistant to Acute Psychosocial Retrieval Stress.

The forward testing effect refers to the finding that testing of previously studied information improves memory for subsequently studied newer information. Recent research showed that the effect is immune to acute psychosocial encoding/retrieval stress, i.e., stress that is induced before initial encoding. The present study investigated whether the forward testing effect is also robust to acute psychosocial retrieval stress, i.e., stress that is induced after encoding but before retrieval of the critical item list. Participants (N = 128) studied three lists of words in anticipation of a final cumulative recall test. Participants were tested immediately on Lists 1 and 2 (testing condition) or restudied the two lists after initial study (restudy condition). After study of the critical List 3, psychosocial stress was induced in half of the participants (stress group), whereas no stress was induced in the other half (control group). The Trier Social Stress Test for Groups (TSST-G) was used for stress induction. Salivary cortisol, alpha amylase, and subjective stress were repeatedly measured. The results of the criterion test showed a generally detrimental effect of psychosocial retrieval stress on List 3 recall. Importantly, the forward testing effect was unaffected by retrieval stress. The findings are discussed with respect to current theories of the forward testing effect.

Reduced eye gaze during facial emotion recognition in chronic depression: Effects of intranasal oxytocin.

Chronic depression disorders (CDD) are characterized by impaired social cognitive functioning. Visual attention during social perception is altered in clinical depression and is known to be sensitive to intranasal treatment with oxytocin (OT). The present study thus investigated potential alterations in gaze preferences during a standardized facial emotion recognition (FER) task using remote eye tracking in patients with CDD and the effect of a single dose of intranasal OT (compared to placebo). In emotion recognition, CDD patients were not more impaired than healthy controls, and there was no OT effect. However, CDD patients (with placebo) demonstrated less attentional preference for the eye region during FER than healthy controls, which was not apparent in the CDD group after OT treatment. Our results suggest that despite largely preserved basic facial emotions recognition, attention in social perception may be altered in CDD, and that this bias may be sensitive to OT treatment. These findings highlight OTs potential as a means of augmenting psychotherapy.

Time-dependent effects of acute stress on working memory performance: A systematic review and hypothesis.

Laboratory procedures such as the Trier Social Stress Test or the (Socially Evaluated) Cold Pressor Test have been used to investigate working memory performance under stress. Researchers so far have reported a diverse spectrum of stress effects (including the lack thereof) on working memory tasks. We conducted a systematic review of the effect acute stress on working memory performance in standardized laboratory procedures. An overview of the existing literature suggests that acute stress affects working memory in a time-dependent manner, presumably due to the differing time scales of the main stress-reactive hormones involved. Based on the empirical evidence, we hypothesize that the immediate stress-induced release of noradrenaline decreases working memory performance within the first 10 min post stress. In addition, rapid cortisol effects impair working memory at a later time-interval beginning about 25 min post stress. We outline future research directions which could further explore the implications of our insights, as for example combined pharmacological and naturalistic stressor interventions.

Increased insula and amygdala activity during selective attention for negatively valenced body parts in binge eating disorder.

Previous studies indicate that participants with eating disorders show an attentional bias for the negatively valenced body parts of their own body. However, the neural basis underlying these processes has not been investigated. We conducted a preregistered combined functional MRI (fMRI)/eye tracking study and presented 35 women with binge eating disorder (BED) and 24 weight-matched control subjects (CG) with body part images of their own body and a weight-matched unknown body. After the fMRI examination, participants rated the attractiveness of the presented body parts. As expected, women with BED responded with significantly higher insula and amygdala activity when viewing the negatively valenced body parts of their own body (compared to all other combinations). However, individuals with BED did not deviate from the CG in the processing of these stimuli in the ventromedial prefrontal cortex, the extrastriate body area or the fusiform body area. Our results indicate that the negative valued body parts carry a particularly strong emotional valence in individuals with BED. These results further emphasize the relevance of processing bias for negatively valenced body parts in the pathology of BED. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Is stress colorblind? Exploring endocrine stress responses in intergroup contexts using a virtual reality-based Trier Social Stress Test (TSST-VR).

Are social stress reactions dependent on the group identities of interaction partners? This study explored the role of ethnic context in modulating endocrine stress responses using a virtual reality (VR)-based adaptation of a standardized stress induction protocol, the Trier Social Stress Test (TSST-VR). Previous research found no clear link between endocrine stress response and ethnic context in the TSST, but conclusions remain limited due to the quasi-experimental nature of manipulating ethnic context in real-life face-to-face interactions. The VR adaptation of the TSST circumvents quasi-experimental limitations and thus provides a first, randomized-controlled investigation of the effects of ethnic context on endocrine stress responses. Forty-three men participated in the study, facing either an ingroup ("White") or an outgroup ("Arab") panel of interviewers. As expected, the TSST-VR produced physiological and subjective stress reactions. However, endocrine stress reactions occurred independent of interviewer ethnicity and could not be predicted based on implicit bias, explicit prejudice, or prejudice-related appearance concerns. Other physiological and subjective stress reactivity parameters also remained comparable across intergroup conditions. Implications for stress research are discussed.

No evidence that gaze anxiety predicts gaze avoidance behavior during face-to-face social interaction.

Eye contact is an indispensable social signal, yet for some individuals it is also a source of discomfort they fear and avoid. However, it is still unknown whether gaze anxiety actually produces avoidant gaze behavior in naturalistic, face-to-face interactions. Here, we relied on a novel dual eye-tracking setup that allows us to assess interactive gaze behavior. To investigate the effect of gaze anxiety on gaze behavior, we a priori created groups of participants reporting high or low levels of gaze anxiety. These participants (n = 51) then performed a semi-standardized interaction with a previously unknown individual reporting a medium level of gaze anxiety. The gaze behavior of both groups did not differ in either classical one-way, eye-tracking parameters (e.g. unilateral eye gaze), or interactive, two-way ones (e.g. mutual gaze). Furthermore, the subjective ratings of both participants' interaction did not differ between groups. Gaze anxious individuals seem to exhibit normal gaze behavior which does not hamper the perceived quality of interactions in a naturalistic face-to-face setup. Our findings point to the existence of cognitive distortions in gaze anxious individuals whose exterior behavior might be less affected than feared by their interior anxiety.

Empathy Modulates the Effects of Acute Stress on Anxious Appearance and Social Behavior in Social Anxiety Disorder.

Patients suffering from social anxiety disorder (SAD) fear social interaction and evaluation, which severely undermines their everyday life. There is evidence of increased prosocial behavior after acute social stress exposure in healthy individuals, which may be interpreted as stress-regulating "tend-and-befriend" behavior. In a randomized controlled trial, we measured empathic abilities in a first diagnostic session. In the following experimental session, we investigated how patients with SAD (n = 60) and healthy control participants (HC) (n = 52) respond to an acute social stressor (Trier Social Stress Test for groups) or a non-stressful control condition, and whether empathic abilities and acute social stress interact to modulate anxious appearance and social behavior in a social conversation test. Salivary cortisol, heart rate, and subjective stress response were repeatedly measured. The anxious appearance and social behavior of participants were rated by the conversation partner. SAD patients demonstrated stronger subjective stress responses while the biological responses did not differ from HC. Moreover, patients performed worse overall in the conversation task, which stress additionally undermined. Finally, we found that both emotional and cognitive empathy buffered the negative effects of acute stress on social behavior in SAD, but not in HC. Our data highlight the importance of empathic abilities for SAD during stressful situations and call for multimodal clinical diagnostics. This may help to differentiate clinical subtypes and offer better-tailored treatment for patients. General Scientific Summary: This study shows that high levels of cognitive and emotional empathy can buffer the negative effects of acute stress on social behavior in social anxiety disorder (SAD). Empathic abilities may be included as an additional diagnostic resource marker for SAD.

Real sweating in a virtual stress environment: Investigation of the stress reactivity in people with primary focal hyperhidrosis.

BACKGROUND: Hyperhidrosis (excessive sweating, OMIM %114110) is a complex disorder with multifactorial causes. Emotional strains and social stress increase symptoms and lead to a vicious circle. Previously, we showed significantly higher depression scores, and normal cortisol awakening responses in patients with primary focal hyperhidrosis (PFH). Stress reactivity in response to a (virtual) Trier Social Stress Test (TSST-VR) has not been studied so far. Therefore, we measured sweat secretion, salivary cortisol and alpha amylase (sAA) concentrations, and subjective stress ratings in affected and non-affected subjects in response to a TSST-VR. METHOD: In this pilot study, we conducted TSST-VRs and performed general linear models with repeated measurements for salivary cortisol and sAA levels, heart rate, axillary sweat and subjective stress ratings for two groups (diagnosed PFH (n = 11), healthy controls (n = 16)). RESULTS: PFH patients showed significantly heightened sweat secretion over time compared to controls (p = 0.006), with highest quantities during the TSST-VR. In both groups, sweating (p < 0.001), maximum cortisol levels (p = 0.002), feelings of stress (p < 0.001), and heart rate (p < 0.001) but not sAA (p = 0.068) increased significantly in response to the TSST-VR. However, no differences were detected in subjective ratings, cortisol concentrations and heart rate between PFH patients and controls (pall > 0.131). CONCLUSION: Patients with diagnosed PFH showed stress-induced higher sweat secretion compared to healthy controls but did not differ in the stress reactivity with regard to endocrine or subjective markers. This pilot study is in need of replication to elucidate the role of the sympathetic nervous system as a potential pathway involved in the stress-induced emotional sweating of PFH patients.

Neural correlates of body image processing in binge eating disorder.

Although body image disturbances play a central role in the development, maintenance and relapse of binge eating disorder (BED), studies investigating the neural basis underlying body processing in BED are still missing. To address this gap, we conducted a preregistered (German Clinical Trials Register [Deutsches Register Klinischer Studien; DRKS], Registration DRKS00008107) combined functional magnetic resonance (fMRI)/eye tracking study in which 38 women with BED and 22 healthy controls weight-matched for overall equivalence processed images of their own bodies, an unfamiliar weight-matched body, and visually matched nonbody control stimuli while performing a one-back task. Women with BED responded with higher left fusiform body area (FBA) activity than controls during body image processing. Despite higher levels of self-reported body dissatisfaction, women with BED did not show overactivation in emotion-processing areas in response to their own body. The eye-tracking results indicated that visual attention toward the presented stimuli was associated with increased activity in the extrastriate body area (EBA) and FBA across groups. Our results thus provide evidence for an aberrant neural processing of body images in BED and highlight the importance of controlling for visual attention in future studies assessing neuronal body processing. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

How to choose the size of facial areas of interest in interactive eye tracking.

Advances in eye tracking technology have enabled the development of interactive experimental setups to study social attention. Since these setups differ substantially from the eye tracker manufacturer's test conditions, validation is essential with regard to the quality of gaze data and other factors potentially threatening the validity of this signal. In this study, we evaluated the impact of accuracy and areas of interest (AOIs) size on the classification of simulated gaze (fixation) data. We defined AOIs of different sizes using the Limited-Radius Voronoi-Tessellation (LRVT) method, and simulated gaze data for facial target points with varying accuracy. As hypothesized, we found that accuracy and AOI size had strong effects on gaze classification. In addition, these effects were not independent and differed in falsely classified gaze inside AOIs (Type I errors; false alarms) and falsely classified gaze outside the predefined AOIs (Type II errors; misses). Our results indicate that smaller AOIs generally minimize false classifications as long as accuracy is good enough. For studies with lower accuracy, Type II errors can still be compensated to some extent by using larger AOIs, but at the cost of more probable Type I errors. Proper estimation of accuracy is therefore essential for making informed decisions regarding the size of AOIs in eye tracking research.

Interoception in preschoolers: New insights into its assessment and relations to emotion regulation and stress.

Interoception may play an important role for emotion regulation and stress, thereby affecting mental health in children and adults. Yet, little is known on interoception in preschool children. Therefore, we investigated interoceptive accuracy using the adapted Jumping Jack Paradigm (JJP) and its relationship with emotion regulation and stress. In Study I, 40 preschoolers completed the JJP and an emotion regulation task, demonstrating a positive relationship between interoceptive accuracy and emotion regulation at trend level (R² = 0.231, p = .023; ß = .278, p = .073). In Study II, 31 preschoolers completed the adapted JJP before and after an acute laboratory stress test. Higher total cortisol output following acute stress induction was associated with reduced interoceptive accuracy (r = -0.670, p = .017). Extending earlier findings in adults and school-children, the relationship of interoceptive accuracy with emotion regulation and stress highlights the importance to investigate interoception in early childhood.

The modulation of social behavior and empathy via oral contraceptives and female sex hormones.

Oral contraceptives (OC) and endogenous female sex hormones in naturally cycling women (NC) are related to a wide range of psychological variables (eg, cognition and affect). Little research on social behavior has been done. One study documented a tendency towards more prosocial behavior in NC than OC women, but the underlying neuroendocrine mechanisms remain unknown. The sex hormones progesterone and estradiol are potential candidates. We analyzed social decision-making and social behavior in 83 healthy women (38 OC and 45 NC) via the Social Value Orientation (SVO) and in real social interactions within a paradigm adapted from behavioral economics. We also measured empathy, and collected saliva samples to quantify the basal levels of estradiol and progesterone. Our analyses revealed higher levels of prosocial behavior and emotional empathy in NC than in OC women, a finding supported by higher levels of prosocial decisions in NC than OC women in the SVO. Regarding the underlying biological mechanisms, we detected lower progesterone levels in OC than NC women. Exploratory analyses revealed a negative correlation between progesterone and trust on the trend level. We found no correlations between estradiol and behavior. Our findings provide evidence that OC modulate social behavior and initial indications of a possible modulation by progesterone. Further research is needed to replicate our findings and extend them to other social behaviors.

The influence of stress on distractor-response bindings.

Stimuli and responses that occur in close temporal contiguity are bound to each other and stored in short-term episodic traces or event files. A repetition of any of the features within an event file results in the retrieval of the entire event file and can influence responding. Along with task-relevant features, event files also contain task-irrelevant features, which are also bound to responses - distractor-response binding. In the present study, the distractor-response binding effect was examined under stress. Stress was induced via a Cold Pressor Test (CPT) and was manipulated between subjects. Distractor-response binding effects were measures at pre- and post-intervention. The CPT produced reliable effects on cortisol measurements and subjective ratings, however, no difference in the distractor-response binding effects between the groups was observed. Results are discussed against the background of the inconsistent results in the literature with respect to stimulus-response binding and stress.

Stress effects on the oddball P300 and N2 in males and females.

We examined the effect of psychosocial stress on electrophysiological markers of novelty and deviance processing, the N2 and P300, as well as sex differences therein. Participants underwent the Trier Social Stress Test (TSST) or a control procedure, followed by an oddball paradigm. A physiological stress response was induced in both sexes in the TSST condition. Furthermore, a reduced target P300 amplitude was elicited in the TSST condition in fronto-central electrodes, an effect that did not differ in magnitude between both sexes. By contrast, stressor effects on N2 amplitude differed by sex: In females, N2 amplitude was decreased in the TSST condition, while in males, no stress effects were observed. Exploratory correlational analyses suggested that a stress-induced P300 amplitude reduction, at least in males, could be due to a modulation of adrenergic activity. These results are consistent with sex differences in the manner in which stress affects lower-level, stimulus-driven vs. higher-level, more controlled processing stages.

Gaze behavior is associated with the cortisol response to acute psychosocial stress in the virtual TSST.

BACKGROUND: The Trier Social Stress Test (TSST) is a reliable tool for psychobiological stress induction. Because of its socio-evaluative nature, it has been useful for investigating gaze behavior. It has been shown that healthy people avoid looking toward faces when under stress, a finding that corroborates studies demonstrating avoidance of eye contact in social anxiety disorder. Yet, little is known about the relationship between gaze behavior and the biological stress response. METHODS: In a final sample of 74 healthy males, a virtual reality version of the Trier Social Stress Test (TSST-VR) with an integrated eye tracker was implemented to investigate gaze behavior during acute stress induction. Stress response measures were collected via saliva samples and subjective stress ratings. Additional questionnaires were administered for examining the influence of social anxiety traits. RESULTS: The TSST-VR elicited a significant psychobiological stress response. Overall, higher gaze times on judges compared to surroundings were found in the speech task while this pattern was reversed in the arithmetic task. Critically, there was a significant negative association between gaze time on judges and cortisol output in cortisol responders. CONCLUSIONS: In a non-clinical sample, avoidance of gaze is associated with a stronger cortisol response to acute stress. This study demonstrates the potential of eye tracking to disentangle the effects of acute stress on social interaction, warranting further investigation in clinical populations characterized by high levels of anxiety in social situations, such as social anxiety and autism spectrum disorder.