Association between Cold Face Test‐induced vagal inhibition and cortisol response to acute stress

Low vagal function is related to several disorders. One possible underlying mechanism linking the vagus nerve and disorders is the HPA axis. Thirty‐three healthy male subjects participated in a stress task, while heart rate (HR), respiratory sinus arrhythmia (RSA), salivary cortisol, and mood were assessed. Vagal function was determined using baseline, stress‐induced inhibition, and Cold Face Test (CFT)‐induced stimulation. The stress task induced a significant increase in cortisol and HR, a decrease in RSA, and a worsening of mood. A linear regression model with the time from CFT onset until maximum bradycardia as the independent variable explained 17.9% of the total variance in cortisol in response to the stressor (mood: 36.5%). The results indicate that a faster CFT response is associated with reduced cortisol increase and enhanced mood after acute stress. Our data support an inverse relationship between vagal function and the HPA axis.     

Salivary alpha-amylase response to acute psychosocial stress: the impact of age

The impact of stress on health varies across the different stages of human life. Aging is associated with psychobiological changes that could limit our ability to cope with stressors. Therefore, it is crucial to clarify the physiological mechanisms that underlie the stress response and the changes that occur in them as we age. Our aim was to investigate age differences in the salivary alpha amylase (sAA) response to stress, and its relationship with other typical stress biomarkers such as cortisol and heart rate (HR). Sixty-two participants divided into two age groups (younger group: N = 31, age range: 18-35 years; older group: N = 31, age range: 54-71 years) were exposed to the Trier Social Stress Test and a control condition in a crossover design. No age differences were found in the sAA or HR responses to stress. However, the sAA global output was higher in older than younger adults. Additionally, in the stress condition, the total amount of cortisol released was positively related to the total sAA released, while the HR increase was positively related to the sAA increase. Our results do not support the existence of an attenuated autonomic nervous system response to stress in older adults, but rather a heightened sympathetic tone. Furthermore, we found further evidence of the coordination between the hypothalamus-pituitary-adrenal system and the autonomic nervous system in their response to acute psychosocial stress.     

Personality and physiological reactions to acute psychological stress

Stable personality traits have long been presumed to have biological substrates, although the evidence relating personality to biological stress reactivity is inconclusive. The present study examined, in a large middle aged cohort (N = 352), the relationship between key personality traits and both cortisol and cardiovascular reactions to acute psychological stress. Salivary cortisol and cardiovascular activity were measured at rest and in response to a psychological stress protocol comprising 5 min each of a Stroop task, mirror tracing, and a speech task. Participants subsequently completed the Big Five Inventory to assess neuroticism, agreeableness, openness to experience, extraversion, and conscientiousness. Those with higher neuroticism scores exhibited smaller cortisol and cardiovascular stress reactions, whereas participants who were less agreeable and less open had smaller cortisol and cardiac reactions to stress. These associations remained statistically significant following adjustment for a range of potential confounding variables. Thus, a negative personality disposition would appear to be linked to diminished stress reactivity. These findings further support a growing body of evidence which suggests that blunted stress reactivity may be maladaptive.     

Haemodynamic reactions to acute psychological stress and smoking status in a large community sample

Exaggerated haemodynamic reactions to acute psychological stress have been implicated in a number of adverse health outcomes. This study examined, in a large community sample, the cross-sectional associations between haemodynamic reactivity and self-reported smoking status. Blood pressure and heart rate were measured at rest and in response to a 3-minute arithmetic stress task. Participants were classified as current, ex-, or non-smokers by their response to a simple prompt. Smokers had significantly smaller SBP and DBP reactions to acute stress than ex- and non-smokers; current and ex-smokers had lower HR reactivity. These effects remained significant following adjustment for a host of variables likely to be associated with reactivity and/or smoking. Although the act of smoking acutely increases haemodynamic activity, the present findings contribute to a growing body of literature showing that smokers have blunted reactivity to mental stress. They also support the hypothesis that blunted reactivity may be characteristic of a range of dependencies. The present results also suggest that smoking status needs to be considered in the design and analysis of stress reactivity studies.     

Blunted cardiovascular and cortisol reactivity to acute psychological stress: A summary of results from the Dutch Famine Birth Cohort Study

The Dutch Famine Birth Cohort Study is a large population based study of late middle aged, overall healthy men and women whose health has been followed from 50 to 65 years of age. In a sample of 725 cohort members, an extensive psychological stress protocol was performed during which cardiovascular and cortisol responses were measured. In line with many previous studies, results showed that increased blood pressure responsiveness to the stress protocol was associated with an increased risk for hypertension 5 years later. However, decreased cardiovascular and/or cortisol stress reactivity were associated with obesity and the risk of becoming obese, symptoms of depression and anxiety, a poor self-reported health, poor lung function, and poor cognitive function (all p for statistical tests < 0.05). These associations generally survived adjustment for a range of potential confounders, including resting cardiovascular and cortisol activity, commitment to the stress tasks, sex, age, smoking and use of medication. Results from these studies agree with recent evidence that low biological reactivity to acute psychological stress may not always be beneficial for health but instead seems to be a marker for a range of negative health outcomes. Future studies have to point out whether low stress reactivity precedes or follows these negative health outcomes.     

An increase in salivary interleukin-6 level following acute psychosocial stress and its biological correlates in healthy young adults

Although interleukin-6 (IL-6) has been investigated frequently in stress research, knowledge regarding the biological processes of IL-6 in association with psychosocial stress remains incomplete. This study focused on salivary IL-6 and reports its temporal variation and biological correlates following acute psychosocial stress. Fifty healthy young adults (39 male and 11 female students) were subjected to the psychosocial stress test ‘Trier Social Stress Test’ (TSST), wherein the participants were asked to deliver a speech and perform a mental arithmetic task in front of 2 audiences. Collection of saliva samples, measurement of heart rate, and assessment of negative moods by visual analogue scales were conducted before, during, and after TSST. Salivary IL-6 levels increased by approximately 50% in response to the TSST and remained elevated for 20 min after the stress tasks were completed. Cluster analyses revealed that individuals with sustained elevation of IL-6 levels following the TSST exhibited a lower cortisol response compared to individuals with lower IL-6 levels. In the correlation analyses, a greater IL-6 response was associated with a higher heart rate during the mental arithmetic task (r = .351, p < .05) and with a lower cortisol response (r = −.302, p < .05). This study demonstrates that salivary IL-6 levels are elevated for a relatively long period following acute psychosocial stress, and suggests that sympathetic activity and cortisol secretion are involved in elevation of salivary IL-6 levels.     

Sex differences in the interleukin-6 response to acute psychological stress

Interleukin-6 (IL-6), an immune regulator that helps coordinate the inflammatory response, may mediate inflammatory disease exacerbation associated with stress. Twenty men and twenty women completed a single session, comprising baseline (20 min), mental arithmetic task (8 min), and recovery (60 min). Blood samples, taken at baseline, immediately after the task, and at +30 and +60 min recovery were analysed for plasma IL-6. Overall, IL-6 increased linearly from baseline to +60 min recovery, and a sex difference was found in the IL-6 response, with men peaking earlier than women. These findings confirm a small delayed IL-6 increase after acute laboratory stress, and reveal sex differences in the profile of the IL-6 response.     

Cardiovascular and cortisol reactions to acute psychological stress and cognitive ability in the Dutch Famine Birth Cohort Study

Given evidence linking blunted cardiovascular and cortisol reactions to acute stress and a range of adverse behavioral outcomes, the present study examined the associations between cardiovascular and cortisol reactivity and cognitive ability measured independently of the stress task exposure. Cognitive ability was assessed using the Alice Heim-4 test of general intelligence and two memory tasks in 724 men and women who were part of the Dutch Famine Birth Cohort Study. Blood pressure and heart rate, as well as cortisol reactivity, were measured to a battery of three standard acute stress tasks. Poorer cognitive ability was associated with lower cardiovascular reactions to stress and lower cortisol area under the curve. Our results are consistent with recent findings implicating low physiological stress reactivity in a range of adverse behavioral and health outcomes.     

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.     

Gender differences and the relationships of perceived background stress and psychological distress with cardiovascular responses to laboratory stressors

The primary aim of this study was to evaluate the relationships of perceived background stress and self-reported psychological distress on cardiovascular reactivity during acute laboratory stressors. The Perceived Stress Scale (PSS) was used as the measure of perceived background stress, and the General Health Questionnaire (GHQ) was used as the measure of psychological distress. A secondary aim was to examine whether background stress and psychological distress affected the susceptibility to induction of a negative mood using music. Heart rate (HR) and blood pressure (BP) were measured in 149 female and male college students at rest and during a stressful mental arithmetic (MA) task and a mood induction procedure. Higher scores on the GHQ were associated with lower systolic BP reactivity during the MA task by all participants. Higher scores on the PSS and GHQ were also associated with lower diastolic BP and HR reactivity, but only in females. Thus, higher self-reports of background stress and psychological distress tended to result in blunted reactivity to an acute laboratory challenge. Higher levels of background stress and psychological distress were not associated with greater susceptibility to a negative mood induction. This study adds to the growing literature indicating that potentially negative health outcomes may be associated with diminished cardiovascular reactivity under certain conditions.     

DHEA and DHEA-S response to acute psychosocial stress in healthy men and women

This study investigates the effect of acute psychosocial stress on serum concentrations of DHEA and DHEA-S in healthy men and women. Twenty men and 19 women (age 30-50 years) underwent Trier Social Stress Test (TSST). Physiological measurements were performed before, directly after the stress test and after 30 mins of recovery. In both men and women, significantly elevated DHEA and DHEA-S levels were observed in response to the stressor. There was a large inter-individual variation in the magnitude of the response, especially for DHEA but no statistical difference between men and women. Magnitude of the change in the levels of DHEA was found to be positively associated with the magnitude of the changes in ACTH, cortisol and heart rate. Furthermore, the results of this study suggest that the capacity to secrete DHEA and DHEA-S during acute psychosocial stress declines with age.     

Prospective associations between cardiovascular reactions to acute psychological stress and change in physical disability in a large community sample

Exaggerated haemodynamic reactions to acute psychological stress have been implicated in cardiovascular disease outcomes, while lower reactions have been considered benign. This study examined, in a large cohort, the prospective associations between stress reactivity and physical disability. Blood pressure and pulse rate were measured at rest and in response to a stress task. Physical disability was assessed using the OPCS survey of disability at baseline and five years later. Heart rate reactivity was negatively associated with change in physical disability over time, such that those with lower heart rate reactivity were more likely to deteriorate over the following five years. These effects remained significant following adjustment for a number of confounding variables. These data give further support to the recent argument that for some health outcomes, lower or blunted cardiovascular stress reactivity is not necessarily protective.     

Self-reported health and cardiovascular reactions to psychological stress in a large community sample: Cross-sectional and prospective associations

Exaggerated cardiovascular reactions to acute psychological stress have been implicated in a number of adverse health outcomes. This study examined, in a large community sample, the cross-sectional and prospective associations between reactivity and self-reported health. Blood pressure and heart rate were measured at rest and in response to an arithmetic stress task. Self-reported health was assessed concurrently and 5 years later. In cross-sectional analyses, those with excellent/good self-reported health exhibited larger cardiovascular reactions than those with fair/poor subjective health. In prospective analyses, participants who had larger cardiovascular reactions to stress were more likely to report excellent/good health 5 years later, taking into account their reported health status at the earlier assessment. The findings suggest that greater cardiovascular reactivity may not always be associated with negative health outcomes.     

Symptoms of depression and cardiovascular reactions to acute psychological stress: evidence from a population study

Depression and exaggerated cardiovascular reactivity are considered risk factors for cardiovascular disease, possibly as a result of common antecedents, such as altered autonomic nervous system function. We examined the association between depressive symptomatology and cardiovascular reactions to psychological stress in 1608 adults (875 women) comprising 3 distinct age cohorts: 24-, 44-, and 63-year olds. Depression was assessed using the Hospital Anxiety and Depression Scale. Blood pressure and heart rate were measured at baseline and during the paced auditory serial arithmetic test. Depression scores were negatively associated with systolic blood pressure and heart rate reactions, after adjustment for likely confounders such as sex, cohort, occupational status, body mass index, stress task performance score, baseline cardiovascular activity, antidepressant, and antihypertensive medication. The direction of association was opposite to that which would be expected if excessive reactivity were to mediate the association between depression and cardiovascular disease outcomes or if they shared common antecedents.     

Optimism moderates psychophysiological responses to stress in older people with Type 2 diabetes

Optimism is thought to be beneficial for health, and these effects may be mediated through modifications in psychophysiological stress reactivity. Type 2 diabetes (T2D) is associated with reduced cardiovascular responses to stress and heightened cortisol over the day. This study assessed the relationships between optimism, stress responsivity, and daily cortisol output in people with T2D. A total of 140 participants with T2D were exposed to laboratory stress. Heart rate (HR), systolic (SBP), diastolic blood pressure (DBP), and cortisol were measured throughout the session. Cortisol output over the day was also assessed. Optimism and self‐reported health were measured using the revised Life Orientation Test and the Short Form Health Survey. Optimism was associated with heightened SBP and DBP stress reactivity (ps < .047) and lower daily cortisol output (p = .04). Optimism was not related to HR, cortisol stress responses, or the cortisol awakening response (ps > .180). Low optimism was related to poorer self‐reported physical and mental health (ps < .01). Optimism could have a protective role in modulating stress‐related autonomic and neuroendocrine dysregulation in people with T2D.     

Salivary cortisol response to psychosocial stress in patients with first-episode psychosis

AimTo analyze the difference in the salivary cortisol response to psychosocial stress between the patients with the first episode of psychosis (FEP) and the control group.MethodsWe performed a cross-sectional analysis of the baseline measurements of a prospective cohort study conducted from 2015 to 2018 at two Croatian psychiatric hospitals. The study consecutively enrolled 53 patients diagnosed with FEP and 63 healthy controls. The primary outcome was the difference in the changes of salivary cortisol concentration during the stress test. The secondary outcome was the difference in the baseline levels of salivary cortisol between patients with FEP and controls. The tertiary outcome were the correlations of salivary cortisol levels with the results of the Positive and Negative Syndrome Scale for Schizophrenia, Rosenberg Self-Esteem Scale, and the International Personality Item Pool.ResultsPatients with FEP had significantly higher baseline salivary cortisol than controls, but their salivary cortisol increased significantly less during the stress test.ConclusionPatients with FEP respond differently to stressful stimuli than controls, as shown by the increased baseline salivary cortisol and blunted cortisol response, possibly indicating a greater vulnerability to psychosocial stress.

Schizophrenia is one of the most complex psychiatric disorders (1), and in most cases, a long-term condition characterized by alternating periods of acute psychosis and remission. The first episode of psychosis (FEP) is usually preceded by a prodromal phase with non-specific symptoms, followed by psychotic symptoms pertaining to five dimensions: positive, negative, affective, cognitive, and psychomotor. While the pathogenesis is largely unknown, different streams of research consistently show that schizophrenia results from a complex gene-environment interaction (2), in line with the stress-diathesis model of schizophrenia etiology (3). According to this model, genetic and environmental factors lead to vulnerability to schizophrenia (2), and schizophrenia occurs when the vulnerable person experiences “enough” stress (4). For the majority of people, significant distress is associated with major stressors, eg, death in the family, serious illness, or separation (5). However, in persons prone to psychosis significant distress is caused even by minor stressors, also known as daily hassles (6).Response to stress involves the activation of the hypothalamic-pituitary-adrenal axis (HPA): the hypothalamus secretes corticotropin-releasing factor (CRF), which stimulates the secretion of adrenocorticotropic hormone (ACTH) from the front pituitary gland. ACTH then stimulates the release of cortisol from the adrenal gland, causing the cascading effect of several bodily systems (immune, neuroendocrine, inflammatory response to the organism, etc) (7). In the central nervous system, increased cortisol levels can lead to the sensitization of dopaminergic response to stress, which can lead to an excessive dopamine release and psychotic symptoms (6). Indeed, various indicators of altered stress response have been confirmed in the population at risk for psychosis compared with healthy population (8,9).While it has been suggested that persons with schizophrenia show a blunted cortisol response following experimentally induced psychosocial stress (10,11), these findings should be further elucidated considering the heterogeneous research results. Some of these discrepancies may arise from the heterogeneity of the samples and different confounding factors but also from different stress response across illness types and stages (12).Generally, persons with FEP show higher basal cortisol values than the healthy population (8,13,14), a finding that possibly indicates their increased basic HPA hyperactivity, which contributes to their higher vulnerability to stressors. HPA axis hyperactivity indicated by elevated basal cortisol levels in individuals with psychosis is expected to also produce a higher acute elevation of cortisol concentrations in response to acute stressful situation (11). However, studies on FEP are not uniform in their findings (5-7). A small study with eleven medication-naive patients found an attenuated response of cortisol to psychosocial stress (15). Furthermore, Pruessner et al (16) reported significantly lower cortisol levels and systolic blood pressure during the psychosocial stress task in an ultra-high-risk group compared with controls; the lower cortisol levels were associated with higher self-rated stress in the past year. The authors suggested that in these patients attenuated stress response reflects the vulnerability to stressors. A recent study among patients with FEP obtained contrary results, ie, lower salivary cortisol levels at baseline but no difference in the cortisol response during psychosocial stress challenge test compared with healthy controls (17). Another study found no differences in baseline salivary cortisol levels between patients with FEP and controls, but a blunted cortisol response to stressors in FEP, both on and off medication, compared with controls (18). Finally, individuals with schizophrenia have shown lower cortisol levels both in anticipation and after exposure to social stress compared with controls, even though there were no differences in cortisol production rate (19).Of note, people with posttraumatic stress syndrome (20) and those with high anxiety traits (21) showed higher salivary baseline cortisol, but a blunted response to psychosocial stress compared with healthy controls (22), which suggests a deficient acute neuroendocrine stress response.Thus, the aim of our study was to assess the difference in the salivary cortisol response to the psychosocial stress between the patients with FEP and healthy controls. We enrolled only patients with FEP who were homogeneous in age, duration of illness, phase of illness, and with minimal exposure to medication to limit some of the major confounding factors from other studies. We hypothesized that patients with FEP showed higher baseline salivary cortisol levels, which indicates increased basic HPA hyperactivity, and a lower cortisol increase in response to psychosocial stressor compared with HC, as an indicator of an aberrant response to psychosocial stress. Our exploratory aim was to analyze the correlation of other clinical factors, including psychopathology, personality traits, and stressful life events with salivary cortisol levels.     

Acute and conditioned blood pressure changes in relation to social and psychosocial stimuli in rats

The naturally occurring tendency to compete with other rats for territorial space has been used to study individual behavior characteristics and blood pressure reactivity to social stimuli in adult male TMD-S3 rats. The competitive characteristics of the individual rats are consistent in two different social situations (victory and defeat). Blood pressure responses during the victory of home territory rats over intruders was more pronounced in the more competitive animals. In addition to defeat by a trained fighter rat, the experimentals were also psychosocially stimulated by the fighter while it was confined in a small wire mesh cage. The blood pressure response to this event was enhanced by the prior defeat of the test animal by the one now confined to the small cage. This response was more pronounced in competitive rats. This approach has potential as an animal model of etiological processes in socially induced hypertension.     

Differential effects of mild chronic stress on cortisol and S-IgA responses to an acute stressor

While acute stress is adaptive in the short term, chronic stress may interfere with HPA axis functioning and self-regulation that can, in turn, alter the body's immune response. Several studies suggest that acute and chronic stress consistently increase cortisol levels; however, the same cannot be said about S-IgA levels. We tested the effects of a mild chronic stress (an academic exam period), on cortisol and S-IgA responses to an acute stress. Exposure to an acute stressor significantly increases cortisol levels during periods of no-stress, but not during mild chronic stress, while S-IgA levels consistently increase during both sessions. Furthermore, we find that during the period of chronic mild stress, the perception of stress is related to increased cortisol response to an acute stressor. Combined, these findings shed light on the impact of increased background stress on acute stress responses.     

Forced expiratory volume is associated with cardiovascular and cortisol reactions to acute psychological stress

It has been argued that blunted cardiovascular and cortisol reactions to acute psychological stress reflect a dysregulation of the neural system that supports motivation. We examined the association between forced expiratory volume in 1 s, an effort (hence motivation) dependent measure of lung function measured by spirometry, and cardiovascular and cortisol reactions to a battery of standard psychological stress tasks, assessed 7 years later. Irrespective of how it was expressed, low forced expiratory volume was associated with blunted heart rate and cortisol stress reactivity. The association survived adjustment for smoking, a range of anthropometric and sociodemographic covariates, and commitment to the stress tasks, as well as cognitive ability.     

Brief Reports: Further evidence for an association between self‐reported health and cardiovascular as well as cortisol reactions to acute psychological stress

In a recent study, the association between cardiovascular reactions to acute psychological stress and self‐reported health was examined. Participants with excellent or good self‐reported health exhibited higher cardiovascular reactivity than those who reported fair or poor health. We investigated this association in a population‐based cohort of whom 725 men and women, aged 55–60 years, participated in a standardized psychological stress test. We measured continuous blood pressure and heart rate as well as cortisol reactivity. Good subjective health was associated with higher cardiovascular and cortisol reactions to psychological stress. Results of the present study confirm those of the previously reported study showing that greater cardiovascular reactivity may not always be associated with negative health outcomes. In addition, the same holds for cortisol reactivity.