Sex differences in emotional and physiological responses to the Trier Social Stress Test

Women are more likely than men to be diagnosed with depression and anxiety-related disorders, and it has been hypothesized that this difference is related to sex differences in stress reactivity. Women typically report higher levels of negative affect than men in response to psychosocial stressors, but the evidence for sex differences in physiological reactivity to stressful situations is not consistent. The present study sought to expand this work by evaluating sex differences in reactivity to a social stress challenge across neuroendocrine, autonomic and affective response domains. Participants (32 women, 30 men) completed a standardized psychosocial stress challenge (i.e., the Trier Social Stress Test (TSST)), during which several physiological (e.g., cortisol reactivity, heart rate) and psychological (e.g., depression, irritability, anger, fear) measures were assessed. The findings demonstrated that cortisol reactivity and the magnitude of autonomic responding failed to reliably discriminate between women and men. However, women reported more fear, irritability, confusion and less happiness immediately following the TSST compared to men. The broader implications of these results and how they relate to sex differences in the etiology and clinical presentation of anxiety and mood disorders are discussed.     

Trained men show lower cortisol, heart rate and psychological responses to psychosocial stress compared with untrained men

Physical activity has proven benefits for physical and psychological well-being and is associated with reduced responsiveness to physical stress. However, it is not clear to what extent physical activity also modulates the responsiveness to psychosocial stress. The purpose of this study was to evaluate whether the reduced responsiveness to physical stressors that has been observed in trained men can be generalized to the modulation of physiological and psychological responses to a psychosocial stressor. Twenty-two trained men (elite sportsmen) and 22 healthy untrained men were exposed to a standardized psychosocial laboratory stressor (Trier Social Stress Test). Adrenocortical (salivary free cortisol levels), autonomic (heart rate), and psychological responses (mood, calmness, anxiety) were repeatedly measured before and after stress exposure. In response to the stressor, cortisol levels and heart rate were significantly increased in both groups, without any baseline differences between groups. However, trained men exhibited significantly lower cortisol and heart rate responses to the stressor compared with untrained men. In addition, trained men showed significantly higher calmness and better mood, and a trend toward lower state anxiety during the stress protocol. On the whole, elite sportsmen showed reduced reactivity to the psychosocial stressor, characterized by lower adrenocortical, autonomic, and psychological stress responses. These results suggest that physical activity may provide a protective effect against stress-related disorders.     

Sex differences in physiological reactivity to acute psychosocial stress in adolescence

Females begin to demonstrate greater negative affective responses to stress than males in adolescence. This may reflect the concurrent emergence of underlying differences in physiological response systems, including corticolimbic circuitries, the hypothalamic-pituitary-adrenal axis (HPAA), and the autonomic nervous system (ANS). This review examines when sex differences in physiological reactivity to acute psychosocial stress emerge and the directionality of these differences over development. Indeed, the literature indicates that sex differences emerge during adolescence and persist into adulthood for all three physiological response systems. However, the directionality of the differences varies by system. The emerging corticolimbic reactivity literature suggests greater female reactivity, particularly in limbic regions densely innervated by gonadal hormone receptors. In contrast, males generally show higher levels of HPAA and ANS reactivity. We argue that the contrasting directionality of corticolimbic and peripheral physiological responses may reflect specific effects of gonadal hormones on distinct systems and also sex differences in evolved behavioral responses that demand different levels of peripheral physiological activation. Studies that examine both subjective reports of negative affect and physiological responses indicate that beginning in adolescence, females respond to acute stressors with more intense negative affect than males despite their comparatively lower peripheral physiological responses. This dissociation is not clearly explained by sex differences in the strength of the relationship between physiological and subjective responses. We suggest that females' greater subjective responsivity may instead arise from a greater activity in brain regions that translate stress responses to subjective awareness in adolescence. Future research directions include investigations of the role of pubertal hormones in physiological reactivity across all systems, examining the relationship of corticolimbic reactivity and negative affect, and sex differences in emotion regulation processes.     

The level of physical activity affects adrenal and cardiovascular reactivity to psychosocial stress

Physical activity plays a key role in the control of neuroendocrine, autonomic, and behavioral responses to physical and psychosocial stress. However, little is known about how the level of physical activity modulates stress responsiveness. Here, we test whether different levels of physical activity are associated with different adrenal, cardiovascular, and psychological responses to psychosocial stress. In addition, competitiveness is assessed as a personality trait that possibly modulates the relationship between physical activity and stress reactivity. Eighteen elite sportsmen, 50 amateur sportsmen, and 24 untrained men were exposed to a standardized psychosocial laboratory stressor (Trier Social Stress Test). Repeated measures of salivary free cortisol, heart rate, and psychological responses to psychosocial stress were compared among the 3 study groups. Elite sportsmen exhibited significantly lower cortisol, heart rate, and state anxiety responses compared with untrained subjects. Amateur sportsmen showed a dissociation between sympathetic and hypothalamic-pituitary-adrenal responsiveness to stress, with significantly reduced heart rate responses but no difference in cortisol responses compared with untrained men. Different levels of competitiveness among groups did not mediate stress reactivity. Our results are in line with previous studies indicating reduced reactivity of the autonomic nervous system to psychosocial stress in trained individuals. More importantly, these findings imply a differential effect of the level of physical activity on different stress-related neurophysiological systems in response to psychosocial stress.     

Sex-specific interaction between cortisol and striato-limbic responses to psychosocial stress

Although women and men differ in psychological and endocrine stress responses as well as in the prevalence rates of stress-related disorders, knowledge on sex differences regarding stress regulation in the brain is scarce. Therefore, we performed an in-depth analysis of data from 67 healthy participants (31 women, taking oral contraceptives), who were exposed to the ScanSTRESS paradigm in a functional magnetic resonance imaging study. Changes in cortisol, affect, heart rate and neural activation in response to psychosocial stress were examined in women and men as well as potential sex-specific interactions between stress response domains. Stress exposure led to significant cortisol increases, with men exhibiting higher levels than women. Depending on sex, cortisol elevations were differently associated with stress-related responses in striato-limbic structures: higher increases were associated with activations in men but with deactivations in women. Regarding affect or heart rate responses, no sex differences emerged. Although women and men differ in their overall stress reactivity, our findings do not support the idea of distinct neural networks as the base of this difference. Instead, we found differential stress reactions for women and men in identical structures. We propose considering quantitative predictors such as sex-specific cortisol increases when exploring neural response differences of women and men.     

Sex differences in stress responses: social rejection versus achievement stress.

BACKGROUND: Sex differences in stress responses may be one mechanism underlying gender differences in depression. We hypothesized that men and women would show different adrenocortical responses to different stressors. In particular, we predicted that women would show greater responses to social rejection stressors, whereas men would demonstrate greater responses to achievement stressors. METHODS: Following a rest session in which they habituated to the laboratory, 50 healthy volunteers (24 men and 26 women, mean age 19.1, SD = 1.13) were randomly assigned to achievement or rejection stress conditions. The achievement condition involved a mathematical and a verbal challenge; the rejection condition involved two social interaction challenges. Self-reported affect and salivary cortisol were measured throughout each stress session (baseline, stress, and poststress periods). RESULTS: There were no sex differences in mood ratings following the stressors; however, cortisol responses showed the predicted gender by condition by time interaction. Men showed significantly greater cortisol responses to the achievement challenges, but women showed greater cortisol responses to the social rejection challenges. CONCLUSIONS: Women appear more physiologically reactive to social rejection challenges, but men react more to achievement challenges. Women's greater reactivity to rejection stress may contribute to the increased rates of affective disorders in women.     

Sex-specific effects of mindfulness on romantic partners’ cortisol responses to conflict and relations with psychological adjustment

Mindfulness is known to improve individuals’ and couples’ subjective stress regulation, but little is known about how it impacts hypothalamic–pituitary–adrenal (HPA) axis responses to acute psychosocial stress. The current study tested effects of dispositional mindfulness facets on young adult couples’ cortisol responses to a conflict discussion stressor, as well as associations with psychological adjustment. One hundred heterosexual couples completed the five facet mindfulness questionnaire one week before engaging in a conflict discussion task. Each partner provided five saliva samples from pre- to post-conflict, which were assayed for cortisol. Measures of adjustment – depression and anxiety symptoms and global well-being – were also completed at this session. Hierarchical linear modeling of cortisol trajectories revealed sex-specific effects; whereas women's mindfulness (nonreactivity facet) predicted higher conflict stress cortisol levels, men's mindfulness (describing facet) predicted less pronounced cortisol reactivity/recovery curves. These patterns were related to better adjustment—lower depression symptoms for women and greater well-being for men. Implications for sex differences in mindfulness benefits are discussed.     

Evolutionary functions of early social modulation of hypothalamic-pituitary-adrenal axis development in humans

The hypothalamic-pituitary-adrenal axis (HPAA) is highly responsive to social challenges. Because stress hormones can have negative developmental and health consequences, this presents an evolutionary paradox: Why would natural selection have favored mechanisms that elevate stress hormone levels in response to psychosocial stimuli? Here we review the hypothesis that large brains, an extended childhood and intensive family care in humans are adaptations resulting from selective forces exerted by the increasingly complex and dynamic social and cultural environment that co-evolved with these traits. Variations in the modulation of stress responses mediated by specific HPAA characteristics (e.g., baseline cortisol levels, and changes in cortisol levels in response to challenges) are viewed as phenotypically plastic, ontogenetic responses to specific environmental signals. From this perspective, we discuss relations between physiological stress responses and life history trajectories, particularly the development of social competencies. We present brief summaries of data on hormones, indicators of morbidity and social environments from our long-term, naturalistic studies in both Guatemala and Dominica. Results indicate that difficult family environments and traumatic social events are associated with temporal elevations of cortisol, suppressed reproductive functioning and elevated morbidity. The long-term effects of traumatic early experiences on cortisol profiles are complex and indicate domain-specific effects, with normal recovery from physical stressors, but some heightened response to negative-affect social challenges. We consider these results to be consistent with the hypothesis that developmental programming of the HPAA and other neuroendocrine systems associated with stress responses may facilitate cognitive targeting of salient social challenges in specific environments.     

Persistent effects of cognitive-behavioral stress management on cortisol responses to acute stress in healthy subjects--a randomized controlled trial

Psychosocial stress leads to a release of cortisol. While this psychoneuroendocrine response helps to maintain physiological as well as psychological equilibrium under stress, exaggerated secretion of cortisol has been shown to have negative effects on somatic health and cognitive functioning. The study set out to examine the long-term effects of cognitive-behavioral stress management training on cortisol stress responses in healthy men and women. Eighty-three healthy subjects were randomly assigned to cognitive-behavioral stress management (CBSM) training or a control condition. Four months after the CBSM, 76 subjects underwent a standardized psychosocial stress test. Salivary cortisol responses were assessed repeatedly before and after the stress test. Subjects in the CBSM group showed significantly reduced cortisol stress responses. With regard to gender, this effect was observed in both men and women. However, the magnitude of the CBSM effect on cortisol responses was smaller in women than in men. Use of oral contraceptives in women influenced the cortisol response, but did not have an impact on the CBSM effect on cortisol. The results show that the previously reported attenuation of cortisol stress responses through CBSM persists and are observable in both men and women. Since stress-induced alterations of hypothalamus pituitary adrenal axis functioning are discussed to be involved in the onset and maintenance of both somatic and psychiatric conditions, similar interventions could be used for prevention and therapy of these detrimental stress effects.     

HPA axis responses to laboratory psychosocial stress in healthy elderly adults, younger adults, and children: impact of age and gender

Data from five independent studies were reanalyzed in order to investigate the impact of age and gender on HPA axis responses to an acute psychosocial laboratory stress task. The total sample consisted of 102 healthy subjects with 30 older adults (mean age: 67.3 y), 41 young adults (mean age: 23.5 y), and 31 children (mean age: 12.1 y). All participants were exposed to the Trier Social Stress Test (TSST).The stress protocol caused highly significant ACTH and total plasma cortisol responses in older and younger male and female adults (all p<0.0001) as well as salivary free cortisol responses in all six age and gender groups (all p<0.0001). Three-way ANOVAs for repeated measurement were applied to investigate the impact of age and gender on ACTH and cortisol responses. Results showed that the ACTH response to stress was higher in younger adults compared to older adults (main effect: p=0.009, interaction: p=0.06). Post hoc analyses revealed that there was no age effect in the subgroup of women (p=n.s.), while younger men had higher ACTH responses compared to older men (p=0.01). For total plasma cortisol, ANOVA results showed that the pattern of reactivity did not differ between age and gender groups (all interactional effects p=n.s.), although older females had hightened overall cortisol levels compared to the other groups, as proofed in post hoc analyses (all p<0.05). For free salivary cortisol, a significant main effect of gender (p=0.05) and an almost significant three-way-interaction (p=0.09) emerged. Post hoc analyses showed an elevated overall free salivary cortisol response in elderly men compared to elderly women (p=0.006), while no gender differences emerged in neither young adults nor children (both p=n.s.).In sum, the stressor induced significant HPA axis responses in all age and gender groups. The observed ACTH response patterns in young and elderly adults may suggest that a heightened hypothalamic drive in young men decreases with age, resulting in similar ACTH responses in elderly men and women. Alternative interpretations are also discussed. The data also supports the idea of a greater adrenal cortex sensitivity to ACTH signals in young females. Free salivary cortisol responses were elevated in elderly men compared to elderly women, an effect which cannot be explained by gender differences in perceived stress responses to the TSST. It can be speculated if corticosteroid binding globulin (CBG) and/or sex steroids are important modulators of these effects.     

The relation between emotion regulation strategies and physiological stress responses in middle childhood

The current study sought to examine whether children's spontaneous use of the emotion regulation strategies suppression and reappraisal during a psychosocial stress task was related to their cortisol and alpha-amylase responses to that task. Salivary cortisol and alpha-amylase responses to a psychosocial stress task were assessed in 158 10-year-old children (83 girls). The children completed a self-report questionnaire measuring use of reappraisal and suppression during the task. Results showed overall increases in cortisol and alpha-amylase in response to the stressor, with higher cortisol reactivity in girls than in boys. With regard to emotion regulation, more use of suppression was related to lower cortisol reactivity in girls, and lower alpha-amylase reactivity and quicker alpha-amylase recovery in all children. The use of reappraisal was not related to the children's cortisol or alpha-amylase responses. The current study is the first to investigate the relation between the spontaneous use of reappraisal and suppression, and physiological stress responses to a psychosocial stressor in children. Our results indicate that reappraisal and suppression are used and can be measured even in 10-year-olds. At this age reappraisal appears ineffective at down-regulating physiological responses, while suppression was related to lower physiological responses. For cortisol reactivity there was a sex difference in the relation with suppression, indicating the importance of including sex as a moderator variable in research studying stress reactivity and its correlates in this age group.     

Men and women differ in inflammatory and neuroendocrine responses to endotoxin but not in the severity of sickness symptoms

Impaired mood and increased anxiety represent core symptoms of sickness behavior that are thought to be mediated by pro-inflammatory cytokines. Moreover, excessive inflammation seems to be implicated in the development of mood/affective disorders. Although women are known to mount stronger pro-inflammatory responses during infections and are at higher risk to develop depressive and anxiety disorders compared to men, experimental studies on sex differences in sickness symptoms are scarce. Thus, the present study aimed at comparing physiological and psychological responses to endotoxin administration between men and women. Twenty-eight healthy volunteers (14 men, 14 women) were intravenously injected with a low dose (0.4 ng/kg) of lipopolysaccharide (LPS) and plasma concentrations of cytokines and neuroendocrine factors as well as negative state emotions were measured before and until six hours after LPS administration. Women exhibited a more profound pro-inflammatory response with significantly higher increases in tumor necrosis factor (TNF)-α and interleukin (IL)-6. In contrast, the LPS-induced increase in anti-inflammatory IL-10 was significantly higher in men. The cytokine alterations were accompanied by changes in neuroendocrine factors known to be involved in inflammation regulation. Endotoxin injection induced a significant increase in noradrenaline, without evidence for sex differences. The LPS-induced increase in cortisol was significantly higher in woman, whereas changes in dehydroepiandrosterone were largely comparable. LPS administration also increased secretion of prolactin, but only in women. Despite these profound sex differences in inflammatory and neuroendocrine responses, men and women did not differ in endotoxin-induced alterations in mood and state anxiety or non-specific sickness symptoms. This suggests that compensatory mechanisms exist that counteract the more pronounced inflammatory response in women, preventing an exaggerated sickness response. Disturbance of these compensatory mechanisms by environmental factors such as stress may promote the development of affective disorders in women.     

Cortisol and ACTH responses to psychosocial stress are modulated by corticosteroid binding globulin levels

The hypothalamus-pituitary-adrenal (HPA) axis is vital for an organisms' response to physiological and psychological stress. Cortisol, secreted upon activation of the HPA axis, impacts on physiological systems throughout the organism. Responses to cortisol are influenced and modified by a number of factors, including corticosteroid binding globulin (CBG) levels. A major part of circulating cortisol is bound to CBG and only the unbound fraction is thought to be biologically active. The aim of the present study was to examine the modulating effect of CBG levels on hormonal responses following psychosocial stress in women using oral contraceptives (n=115) and in medication-free men (n=93). In women, CBG levels were negatively associated with ACTH and salivary cortisol and positively with total cortisol levels following the TSST. In men, positive associations were observed between CBG and ACTH and total cortisol levels following the TSST. CBG is an important regulatory element of HPA axis response patterns; therefore, CBG levels have to be taken into account as a potential modifier of ACTH and cortisol responses to psychosocial and pharmacological stimulation. Investigations of the consequences of long-lasting OC intake on the neuroendocrine stress regulation in women might be warranted.     

Effects of different kinds of couple interaction on cortisol and heart rate responses to stress in women

In animal studies, positive social interaction and physical contact play a preeminent role in the control of behavioral and neuroendocrine responses to stress. The aim of this study was to determine whether specific kinds of couple interaction reduce hypothalamic-pituitary-adrenal (HPA) and autonomic responses to psychosocial stress in women. Sixty-seven women, aged 20-37 years, who had been married or cohabiting with a male partner for at least 12 months at the time of the study, were exposed to a standardized psychosocial laboratory stressor (Trier Social Stress Test). Participants were randomly assigned to three study groups differing in the type of a 10-min period of social interaction with their partner prior to stress: n=25 with no partner interaction, n=22 with verbal social support, and n=20 with physical contact (standardized neck and shoulder massage). Salivary free cortisol levels, plasma levels of oxytocin, heart rate, and psychological responses to stress were compared among the three study groups. Women with positive physical partner contact before stress exhibited significantly lower cortisol and heart rate responses to stress but no different plasma oxytocin levels compared to women who received social support or no social interaction. Verbal social support alone was not associated with reduced stress responsiveness. Our results are in line with previous human studies indicating reduced responsiveness to verbal social support by a spouse in women. More importantly, these findings imply a direct protective effect of touch on stress-related neurobiological systems as a possible underlying mechanism of health beneficial effects of positive couple interaction.     

Adult attachment and social support interact to reduce psychological but not cortisol responses to stress

OBJECTIVE: Adult attachment has been suggested to mediate the effect of social support on stress protection. The purpose of this study was to investigate the effects of adult attachment and social support on psychological and endocrine responses to psychosocial stress. METHODS: Sixty-three healthy men who were married or cohabiting were randomly assigned to receive either instructed social support from their partner or no social support before being exposed to a standardized psychosocial stressor (Trier Social Stress Test). Attachment was determined using the Experiences in Close Relationships-Revised questionnaire. State anxiety, mood, and salivary cortisol levels were repeatedly assessed before and after stress. RESULTS: Secure attachment was associated with stronger decreases in state anxiety levels following stress exposure. More importantly, the combination of social support and secure attachment exhibited the lowest anxiety levels after stress (interaction effect). Social support alone reduced cortisol responses to stress, whereas secure attachment did not influence cortisol concentrations. CONCLUSION: This first study on the interaction of adult attachment and social support in terms of psychological and endocrine stress responses concurs with previous studies suggesting an important protective role of attachment for psychological stress responsiveness. However, attachment did not directly moderate cortisol responses to acute stress.     

Human hypothalamus–pituitary–adrenal axis responses to acute psychosocial stress in laboratory settings

Cumulative acute psychosocial stress is thought to promote the development of a range of disorders which suggests that biomarkers for the physiological response may become valuable tools for biomedical research and development. The search for these biomarkers has been aided by the development of a standardised protocol for inducing psychosocial stress that combines social-evaluative threat and uncontrollability, i.e., the Trier Social Stress Test (TSST). Among other biological markers of acute stress, this test induces significant changes of the hypothalamus–pituitary–adrenal axis (HPAA), which is thought to play a pivotal role in the generation of stress-associated pathologies. The HPAA responses show differences between patients and healthy subjects as well as between pathologies. Moreover, gender, age, personality traits, social environment, and genotype can also shape the individual's acute stress response triggered by the TSST. Characterization of the roles and interactions of these factors in generating a dysregulation of the neuroendocrine responses to acute psychosocial stress await longitudinal studies.     

Human hypothalamus-pituitary-adrenal axis responses to acute psychosocial stress in laboratory settings

Cumulative acute psychosocial stress is thought to promote the development of a range of disorders which suggests that biomarkers for the physiological response may become valuable tools for biomedical research and development. The search for these biomarkers has been aided by the development of a standardised protocol for inducing psychosocial stress that combines social-evaluative threat and uncontrollability, i.e., the Trier Social Stress Test (TSST). Among other biological markers of acute stress, this test induces significant changes of the hypothalamus-pituitary-adrenal axis (HPAA), which is thought to play a pivotal role in the generation of stress-associated pathologies. The HPAA responses show differences between patients and healthy subjects as well as between pathologies. Moreover, gender, age, personality traits, social environment, and genotype can also shape the individual's acute stress response triggered by the TSST. Characterization of the roles and interactions of these factors in generating a dysregulation of the neuroendocrine responses to acute psychosocial stress await longitudinal studies.     

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

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

Irritable bowel syndrome: does gender matter?

In industrialized parts of the world, women seek health care services for irritable bowel syndrome (IBS) more frequently than men. The role of gender in IBS is likely multifactorial involving inherent physiological differences in gonadal hormones, stress reactivity, and inflammatory responses, as well as sociocultural differences in response to pain and/or bowel pattern changes. This mini-review in particular addresses gender differences in visceral sensitivity, motility, and autonomic nervous system balance as potential factors contributing to gender differences in IBS presentation.     

Sex differences in stress-related psychiatric disorders: Neurobiological perspectives

Stress is associated with the onset and severity of several psychiatric disorders that occur more frequently in women than men, including posttraumatic stress disorder (PTSD) and depression. Patients with these disorders present with dysregulation of several stress response systems, including the neuroendocrine response to stress, corticolimbic responses to negatively valenced stimuli, and hyperarousal. Thus, sex differences within their underlying circuitry may explain sex biases in disease prevalence. This review describes clinical studies that identify sex differences within the activity of these circuits, as well as preclinical studies that demonstrate cellular and molecular sex differences in stress responses systems. These studies reveal sex differences from the molecular to the systems level that increase endocrine, emotional, and arousal responses to stress in females. Exploring these sex differences is critical because this research can reveal the neurobiological underpinnings of vulnerability to stress-related psychiatric disorders and guide the development of novel pharmacotherapies.