Petra H. Wirtz

The Neural Correlates of Sex Differences in Emotional Reactivity and Emotion Regulation

Sex differences in emotional responding have been repeatedly postulated but less consistently shown in empirical studies. Because emotional reactions are modulated by cognitive appraisal, sex differences in emotional responding might depend on differences in emotion regulation. In this study, we investigated sex differences in emotional reactivity and emotion regulation using a delayed cognitive reappraisal paradigm and measured whole‐brain BOLD signal in 17 men and 16 women. During fMRI, participants were instructed to increase, decrease, or maintain their emotional reactions evoked by negative pictures in terms of cognitive reappraisal. We analyzed BOLD responses to aversive compared to neutral pictures in the initial viewing phase and the effect of cognitive reappraisal in the subsequent regulation phase. Women showed enhanced amygdala responding to aversive stimuli in the initial viewing phase, together with increased activity in small clusters within the prefrontal cortex and the temporal cortex. During cognitively decreasing emotional reactions, women recruited parts of the orbitofrontal cortex, the anterior cingulate, and the dorsolateral prefrontal cortex to a lesser extent than men, while there was no sex effect on amygdala activity. In contrast, compared to women, men showed an increased recruitment of regulatory cortical areas during cognitively increasing initial emotional reactions, which was associated with an increase in amygdala activity. Clinical implications of these findings are discussed. Hum Brain Mapp, 2010.

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.

Perfectionism and the cortisol response to psychosocial stress in men.

Objective: To test the hypothesis that perfectionism is an important moderator of the neuroendocrine stress response, with higher perfectionism predicting increased neuroendocrine activation. Methods: A total of 50 middle-aged men underwent an acute standardized psychosocial stress task (Trier Social Stress Test). Perfectionism, cognitive appraisal of the stressful situation, trait anxiety, and various personality characteristics were assessed with questionnaires. Salivary cortisol, plasma epinephrine and norepinephrine, blood pressure, and heart rate were analyzed before and after stress. Circadian profiles of cortisol secretion during the day and in response to awakening were analyzed to assess basal activity of the hypothalamus-pituitary-adrenal (HPA) axis. Multiple regression analyses were conducted to identify predictors of the neuroendocrine stress response. Results: Perfectionism was significantly associated with area under the total response curve with respect to increase (AUCi) of cortisol (r = 0.322, p = .046), but not with AUCi of norepinephrine (r = −0.217, p = .152) or AUCi of epinephrine (r = 0.116, p = .477). Hence, AUCi of cortisol was the main criterion. As possible predictors, trait anxiety, neuroticism, vital exhaustion, secondary appraisal, depression, and openness were considered. Regression analyses demonstrated that only perfectionism (&bgr; = 0.45, p = .002) and secondary appraisal (&bgr; = 0.50, p = .001) were independent predictors of AUCi of cortisol, the final model explaining 45% of the total variance in cortisol response (R2 = 0.45, “shrunken” R2 [sR2] = 0.38); perfectionism alone accounted for 18% of this variance (&Dgr;R2 = 0.18, sR2 = 0.19). Conclusion: The typical cognitions, and presumably the associated emotions, of perfectionists seem to contribute independently to stress-induced bodily responses, including HPA axis activation, in response to psychosocial stress. HPA = hypothalamic-pituitary-adrenal; TSST = Trier Social Stress Test; AUC = area under the curve; HR = heart rate; BP = blood pressure; PASA = primary appraisal secondary appraisal; MPS = Frost Multidimensional Perfectionism Scale; CMD = concern over mistakes and doubts.

Evidence for altered hypothalamus-pituitary-adrenal axis functioning in systemic hypertension: Blunted cortisol response to awakening and lower negative feedback sensitivity

BACKGROUND Hypothalamus-pituitary-adrenal (HPA) axis functioning in systemic hypertension is not fully understood. We explored HPA axis activity and feedback sensitivity to oral administration of dexamethasone in systemic hypertension via assessment of the cortisol awakening response (CAR) and the circadian cortisol profile. METHODS The CAR and circadian cortisol profile were assessed in 20 unmedicated and otherwise healthy middle-aged hypertensive men and in 22 normotensive male controls. Salivary free cortisol measures for the CAR were obtained immediately after awakening and 15, 30, 45, and 60 min thereafter. Circadian cortisol secretion was sampled at 08:00, 11:00, 15:00, and 20:00 h. Assessment of the CAR was repeated on the next day after administration of 0.5mg dexamethasone at 23:00 h on the previous night. RESULTS Hypertensives had a significantly lower CAR (p<0.02) and significantly reduced suppression of the CAR after dexamethasone administration (p<0.01) than normotensive controls. There were no significant differences in cortisol levels at awakening and in circadian cortisol profiles between hypertensives and normotensives. CONCLUSION We found evidence for altered HPA axis activity in men with systemic hypertension evident with the CAR. Hypertensives showed relative attenuation in the CAR and in the HPA axis feedback sensitivity following dexamethasone suppression. Such alterations in HPA axis regulation might contribute to the atherosclerotic risk in hypertensive individuals.

Reduced glucocorticoid sensitivity of monocyte interleukin-6 production in male industrial employees who are vitally exhausted.

Objective: Proinflammatory changes are thought to link vital exhaustion with adverse cardiovascular outcomes. Monocytes play a central role in the pathogenesis of atherosclerotic lesions and are a major source of circulating cytokines. We hypothesized that vital exhaustion may alter the regulation of monocyte activity, as measured by lipopolysaccharide (LPS)‐stimulated and glucocorticoid inhibited release of the proinflammatory cytokine interleukin‐6 (IL‐6). Methods: In 166 middle‐aged apparently healthy men, vital exhaustion was measured by the Shortened Maastricht Exhaustion Questionnaire. Subjects in the highest quartile (highly exhausted, N = 38) were compared with those in the second and third quartiles (moderately exhausted N = 89) vs. those in the lowest quartile (nonexhausted, N = 39) in terms of plasma C‐reactive protein (CRP) and tumor necrosis factor‐&agr; (TNF‐&agr;) levels, and as to IL‐6 release after LPS stimulation in vitro. Inhibition of IL‐6 release was determined by coincubation with increasing concentrations of dexamethasone. Monocyte glucocorticoid sensitivity was defined as the dexamethasone concentration inhibiting IL‐6 release by 50%. Results: Highly exhausted individuals had higher CRP levels than nonexhausted subjects (p = .008). LPS‐stimulated IL‐6 release was not significantly different between groups. However, in highly exhausted participants, dexamethasone was less able to inhibit IL‐6 release (p = .010), and the glucocorticoid sensitivity was lower (p = .003) than in nonexhausted subjects. Conclusions: In highly exhausted individuals, glucocorticoids exert less suppressive action on monocyte IL‐6 release than in nonexhausted subjects. This finding points to altered regulation of monocyte cytokine production as one possible pathway linking exhaustion with atherosclerosis.

Higher overcommitment to work is associated with lower norepinephrine secretion before and after acute psychosocial stress in men

BACKGROUND Overcommitment (OC) is a pattern of excessive striving. In reaction to work stress, OC has been associated with higher sympathetic nervous system activation and cortisol release, but data on neuroendocrine reactivity to standardized stressors are scarce. We investigated whether OC is associated with differential levels of the stress hormones norepinephrine and cortisol in response to acute psychosocial stress. METHODS Fifty-eight medication-free non-smoking men aged between 20 and 65 years (mean+/-S.E.M.: 36.3+/-1.8) underwent an acute standardized psychosocial stress task combining public speaking and mental arithmetic in front of an audience. We assessed OC as well as a variety of psychological control variables including vital exhaustion, perfectionism, chronic stress, and cognitive stress appraisal. Moreover, we measured plasma norepinephrine as well as salivary cortisol before and after stress and several times up to 60 min thereafter. RESULTS Higher OC was associated with lower baseline norepinephrine levels (r = -0.37, p < 0.01). General linear models controlling for age, BMI, and mean arterial blood pressure revealed that higher overcommitment was associated with lower norepinephrine and cortisol levels before and after stress (ps < 0.02) as well as with lower norepinephrine stress reactivity (p = 0.02). Additional controlling for the potential psychological confounders vital exhaustion, perfectionism, chronic stress, and depression confirmed lower norepinephrine levels before and after stress (p < 0.01) as well lower norepinephrine stress reactivity (p = 0.02) with increasing OC. Higher OC independently explained 13% of the total norepinephrine stress response (beta = -0.46, p < 0.01, R(2) change = 0.13). CONCLUSIONS Our findings suggest blunted increases in norepinephrine following stress with increasing OC potentially mirroring blunted stress reactivity of the sympathetic nervous system.

Stress-buffering effects of psychosocial resources on physiological and psychological stress response in pregnant women

Sixty healthy pregnant women (aged 21-35 years), including 30 pregnant women at the beginning of second trimester and 30 women at the beginning of third trimester underwent a psychosocial stress test. Physiological (salivary free cortisol levels, salivary alpha-amylase levels) and psychological (perceived stress, mood, anxiety) responses to standardized psychosocial stress have been brought in association with psychosocial resources (self-efficacy and daily uplifts). Predictions revealed that higher resources predict lower physiological and psychological stress responses and higher mood levels. We conclude from our data that psychosocial resources appear to dampen psychological and physiological stress response during pregnancy.

Anticipatory Cognitive Stress Appraisal and the Acute Procoagulant Stress Response in Men

Objective: Acute mental stress elicits blood hypercoagulability. Following a transactional stress model, we investigated whether individuals who anticipate stress as more threatening, challenging, and as exceeding their coping skills show greater stress reactivity of the coagulation activation marker D-dimer, indicating fibrin generation in plasma. Methods: Forty-seven men (mean age 44 ± 14 years; mean blood pressure [MBP] 101 ± 12 mm Hg; mean body mass index [BMI] 26 ± 3 kg/m2) completed the Primary Appraisal Secondary Appraisal (PASA) scale before undergoing the Trier Social Stress Test (combination of mock job interview and mental arithmetic task). Heart rate, blood pressure, plasma catecholamines, and D-dimer levels were measured before and after stress, and during recovery up to 60 minutes poststress. Results: Hemodynamic measures, catecholamines, and D-dimer changed across all time points (p values <.001). The PASA “Stress Index” (integrated measure of transactional stress perception) correlated with total D-dimer area under the curve (AUC) between rest and 60 minutes poststress (r = 0.30, p = .050) and with D-dimer change from rest to immediately poststress (r = 0.29, p = .046). Primary appraisal (combined “threat” and “challenge”) correlated with total D-dimer AUC (r = 0.37, p = .017), D-dimer stress change (r = 0.41, p = .004), and D-dimer recovery (r = 0.32, p = .042). “Challenge” correlated more strongly with D-dimer stress change than “threat” (p = .020). Primary appraisal (&Dgr;R2 = 0.098, &bgr; = 0.37, p = .019), and particularly its subscale “challenge” (&Dgr;R2 = 0.138, &bgr; = 0.40, p = .005), predicted D-dimer stress change independently of age, BP, BMI, and catecholamine change. Conclusions: Anticipatory cognitive appraisal determined the extent of coagulation activation to and recovery from stress in men. Particularly individuals who anticipated the stressor as more challenging and also more threatening had a greater fibrin stress response. AUC = area under the curve; BMI = body mass index; CAD = coronary artery disease; EPI = epinephrine; HR = heart rate; MBP = mean blood pressure; NEPI = norepinephrine; PASA = Primary Appraisal Secondary Appraisal; TSST = Trier Social Stress Test.

Higher body mass index (BMI) is associated with reduced glucocorticoid inhibition of inflammatory cytokine production following acute psychosocial stress in men

BACKGROUND Body mass index (BMI) and mental stress seem to exert part of their cardiovascular risk by eliciting inflammation. However, the adverse effects of stress on inflammatory activity with BMI are not fully understood. We investigated whether higher BMI is associated with reduced glucocorticoid inhibition of inflammatory cytokine production following stress in men while controlling for age and blood pressure. We measured glucocorticoid inhibition of lipopolysaccharide (LPS)-stimulated release of the proinflammatory cytokine tumor necrosis factor (TNF)-alpha. METHODS Forty-two men (age range 21-65 years; BMI range 21-34 kg/m(2)) underwent the Trier Social Stress Test (combination of mock job interview and mental arithmetic task). Whole blood samples were taken immediately before and after stress, and during recovery up to 60 min post-stress. Glucocorticoid sensitivity of LPS-stimulated TNF-alpha expression was assessed in vitro with and without coincubating increasing doses of dexamethasone. Moreover, salivary cortisol was measured during the experiment and on a normal day for assessment of baseline circadian cortisol. RESULTS Higher BMI was associated with lower glucocorticoid sensitivity of monocyte TNF-alpha production after stress (main effect of BMI: p<0.001) and with more pronounced decreases of glucocorticoid sensitivity following stress (interaction of stress-by-BMI: p=0.002). Neither LPS-stimulated TNF-alpha release nor baseline glucocorticoid sensitivity were associated with BMI. Similarly, BMI was not associated with salivary cortisol, either in reaction to stress or in circadian cortisol secretion. CONCLUSIONS Our data suggest that with increasing BMI, glucocorticoids are less able to inhibit TNF-alpha production following stress. This might suggest a new mechanism linking BMI with elevated risk for adverse cardiovascular outcomes following stress.

Taiji practice attenuates psychobiological stress reactivity — A randomized controlled trial in healthy subjects

BACKGROUND Stress reducing effects of Taiji, a mindful and gentle form of body movement, have been reported in previous studies, but standardized and controlled experimental studies are scarce. The present study investigates the effect of regular Taiji practice on psychobiological stress response in healthy men and women. METHODS 70 participants were randomly assigned to either Taiji classes or a waiting list. After 3 months, 26 (8 men, 18 women) persons in the Taiji group and 23 (9 men, 14 women) in the waiting control group underwent a standardized psychosocial stress test combining public speaking and mental arithmetic in front of an audience. Salivary cortisol and α-amylase, heart rate, and psychological responses to psychosocial stress were compared between the study groups. (ClinicalTrials.gov number, NCT01122706.) RESULTS Stress induced characteristic changes in all psychological and physiological measures. Compared to controls, Taiji participants exhibited a significantly lower stress reactivity of cortisol (p = .028) and heart rate (p = .028), as well as lower α-amylase levels (p = .049). They reported a lower increase in perceived stressfulness (p = .006) and maintained a higher level of calmness (p = .019) in response to psychosocial stress. CONCLUSION Our results consistently suggest that practicing Taiji attenuates psychobiological stress reactivity in healthy subjects. This may underline the role of Taiji as a useful mind-body practice for stress prevention.