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.     

Low forced expiratory volume is associated with blunted cardiac reactions to acute psychological stress in a community sample of middle-aged men and women

It has been argued recently that blunted cardiovascular reactions to acute psychological stress have adverse behavioural and health corollaries that reflect dysregulation of the neural systems that support motivation. We examined the association between cardiovascular reactions to a standard stress task, the paced auditory serial arithmetic rest, and forced expiratory volume in one second, an effort, hence motivation, dependent assessment of lung function measured by spirometry. Low forced expiratory volume, expressed as a ratio to height squared was associated with blunted heart rate, but not blood pressure, stress reactivity, r = .17, p < .001. The association survived adjustment for smoking, a range of anthropometric and sociodemographic covariates, resting heart rate and stress task performance, β = .11, p = .005. As such, our results provide support for the hypothesis that blunted stress reactivity may be a peripheral marker of a dysfunction in the brain systems that support motivated behaviour.     

Is the association between depression and blunted cardiovascular stress reactions mediated by perceptions of stress?

Symptoms of depression are related to blunted cardiovascular reactions to acute stress tasks. However, it is unclear what factors might mediate this association and whether blunted responses are specific to mental stress tasks or are also evident with other forms of stress. The present study assessed cardiovascular reactivity to both mental and postural stress and the role of background stress exposure and stress perception. Undergraduate students (N = 119, 81 females) were screened for depressive symptoms using the Beck Depression Inventory. Twenty-six participants with probable depression and 26 non-depressed controls underwent cardiovascular stress testing. Heart rate (HR), systolic (SBP) and diastolic (DBP) blood pressure were measured at rest and in response to a 5 min orthostatic challenge and an 8 min mental arithmetic task. Stress exposure was measured using the Undergraduate Stress Questionnaire. Perceptions of general life stress were assessed using the Perceived Stress Scale (PSS) and perceptions of the stress task impact were measured using Threat Appraisal (TA). Symptoms of depression were associated with blunted HR, F(2,98) = 5.26, p = .010, η² = .097, and SBP, F(2,98) = 6.47, p = .008, η² = .117, reactions to the mental stress but not to postural challenge. HR reactions were mediated by PSS score, while both PSS score and TA emerged independently as mediators of SBP reactions. These results confirm a negative relationship between depressive symptoms and cardiovascular reactions to acute stress, suggest that this association may be stress task-specific, and may be mediated by perceptions of stress.     

High perceived stress in relation to life events is associated with blunted cardiac reactivity

The current study examined whether the perception of life stress related to cardiovascular reactivity. Participants (n = 100) completed the Perceived Stress Scale, the Undergraduate Stress Questionnaire, and undertook a standard mental arithmetic stress task. Blood pressure and pulse rate were measured at baseline, during, and following stress task exposure. Reactivity was the difference between stress and baseline cardiovascular activity. A perceived stress difference score (PSDS) was calculated by subtracting the Undergraduate Stress Questionnaire scores from the Perceived Stress Scale scores. Two groups were created: high PSDS (n = 15; PSDS at least 1 SD above the mean) and low PSDS (n = 15; PSDS at least 1 SD below the mean). There was a significant difference between groups in pulse rate reactivity, F(1,28) = 8.73, p = .006, η² = .24. High PSDS scores were associated with significantly lower pulse rate reactions to stress. Those who perceived their lives as more stressful than their actual stress exposures justified would appear to be characterised by blunted cardiac reactivity.     

Neuroticism, cortisol reactivity, and antibody response to vaccination

This study examined whether neuroticism was related to the antibody response to influenza vaccination and whether the relationship was mediated by cortisol reactions to acute laboratory mental stress. Antibody status was assessed at baseline and to a trivalent influenza vaccination in 57 students at 5-week and 5-month follow-up. Neuroticism was also measured at baseline. Cortisol was measured at rest and in response to a pressurized mental arithmetic task. At both follow-ups, higher neuroticism scores were associated with poorer A/Panama antibody response, following adjustment for baseline antibody titer. Higher neuroticism scores were also associated with blunted cortisol reactivity, and blunted cortisol reactivity was associated with poorer A/Panama antibody response, but only at 5 months. However, there was no conclusive evidence that cortisol reactivity mediated the association between neuroticism and antibody response.     

Preliminary evidence that acute long-chain omega-3 supplementation reduces cardiovascular reactivity to mental stress: a randomized and placebo controlled trial

Objective

Exaggerated cardiovascular reactivity predicts cardiovascular morbidity and mortality. Some evidence suggests that omega-3 fatty acids improve cardiovascular function. The objective of this study was to examine the influence of an acute low dose of long-chain omega-3 fatty acids on young, healthy individuals.

Methods

Participants (n = 34) were randomly assigned to either 21-days of omega-3 fatty acids (1.4 g EPA and DHA) or matched placebo. Cardiovascular measurements were obtained in the laboratory during baseline and during a standard mental arithmetic task, where participants were instructed to engage in serial subtractions by 17s from a four-digit number and cardiovascular reactivity to the task was calculated.

Results

Mean arterial pressure reactivity was significantly reduced by supplementation (F(1,32) = 5. 12, p = .03, η² = .144) but not by placebo.

Conclusion

Supplementation of omega-3 fatty acids may reduce cardiovascular reactivity to stress.     

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.     

Cortisol responses to emotional stress in men: association with a functional polymorphism in the 5HTR2C gene

The serotonin 5HTR2C receptor has been shown to mediate HPA axis activation during stress. We hypothesized that a functional polymorphism (rs6318) of the 5HTR2C gene would be associated with HPA axis response to a laboratory stress protocol. The present sample consisted of 41 men (22 African Americans, 19 Caucasians). We found that at rest men with the more active rs6318 Ser23 C allele had similar cortisol values compared to those with the less active Cys23 G allele. During laboratory stress, however, men with the Ser23 C allele exhibited the predicted significantly higher cortisol levels (p < 0.001), as well as larger increases in anger (p = 0.08) and depressive mood (p = 0.006) ratings, compared to the Cys23 G carriers. The increase in cortisol was significantly related to the increases in ratings of anger and depression assessed before and after the emotion induction, and these correlations became nonsignificant when rs6318 genotype was covaried. We conclude that genetic variation in 5HTR2C may be associated with HPA axis activation and stimulated by emotional stress, and also with both psychological and physiological endophenotypes that increase the risk of cardiovascular disease and type-2 diabetes.     

Heart rate reactivity is associated with future cognitive ability and cognitive change in a large community sample

The relationship between cardiovascular reactions to acute mental challenge in the laboratory and cognitive ability has received scant attention. The present study examined the association between reactivity and future cognitive ability. Heart rate and blood pressure reactions to a mental stress task were measured in 1647 participants comprising three distinct age cohorts. Cognitive ability was assessed using the Alice Heim-4 test of general intelligence and choice reaction time 5 and 12 years later. High heart rate reactivity was related to higher general intelligence scores and faster choice reaction times at both follow-ups. High heart rate reactivity was also associated with a smaller decline in cognitive ability between assessments. These associations were still evident following adjustment for a wide range of potentially confounding variables. The present results are consistent with the notion that high reactivity may not always be a maladaptive response and that low or blunted reactivity may also have negative corollaries.     

Association between smoking status and cardiovascular and cortisol stress responsivity in healthy young men

Acutely, cigarette smoking stimulates increases in blood pressure (BP). heart rate (HR), and cortisol, but little evidence is available concerning the impact of habitual smoking status on cardiovascular stress responsivity. This relation was assessed in 86 healthy male firefighters, age 19 to 31, comprising 52 nonsmokers and 34 smokers. Measures of BP, HR, salivary free cortisol, breathing pattern, and self-reported stress and alertness were obtained while subjects performed nonverbal mental arithmetic and a socially evaluative speech task. Systolic and diastolic BP were higher at rest in nonsmokers than smokers, and a consistent difference in stress responsivity was also found. BP, HR, and cortisol responses to mental arithmetic were significantly smaller in smokers than nonsmokers, with mean changes in BP (adjusted for body weight) averaging 19.3/1 l.0 mmHg and 28.5/15.4 mmHg in smokers and nonsmokers, respectively. There were no effects of smoking status on task performance or subjective stress responses and no differences between groups in family health history, health-related behaviors, or psychological characteristics that might account for the reactivity difference. Possible explanations of the results are discussed, and methodological implications for cardiovascular stress reactivity studies are outlined. This study was supported by the Medical Research Council, UK     

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.     

Measurement of constructs using self-report and behavioral lab tasks: Is there overlap in nomothetic span and construct representation for impulsivity?

There has been little empirical evidence examining the overlap in nomothetic span for self-report measures and construct representation for behavioral lab tasks in most psychological constructs. Using the personality trait of impulsivity as an example, the authors completed a meta-analysis of 27 published research studies examining the relationship between these methods. In general, although there is a statistically significant relationship between multidimensional self-report and lab task impulsivity (r = 0.097), practically, the relationship is small. Examining relationships among unidimensional impulsivity self-report and lab task conceptualizations indicated very little overlap in self-report and behavioral lab task constructs. Significant relationships were found between lack of perseverance and prepotent response inhibition (r = 0.099); between lack of planning and prepotent response inhibition (r = 0.106), delay response (r = 0.134), and distortions in elapsed time (r = 0.104); between negative urgency and prepotent response inhibition (r = 0.106); and between sensation seeking and delay response (r = 0.131). Researchers should take care to specify which particular unidimensional constructs are operationalized with not only impulsivity, but with all traits. If self-report and lab task conceptualizations measure disparate aspects of impulsivity, we, as a field, should not expect large conceptual overlap between these methods.     

Association study between a functional polymorphism of FK506-binding protein 51 (FKBP5) gene and personality traits in healthy subjects

Previous studies have shown that the function of hypothalamic-pituitary-adrenal (HPA) axis is involved in the characterization of personality traits. FK506-binding protein 51 (FKBP51 or FKBP5) is a co-chaperone of heat-shock protein 90, and plays an important role in the negative feedback regulation of HPA axis function. It has been reported that a C/T single nucleotide polymorphism in the intron 2 of FKBP5 gene (rs1360780) affects FKBP5 protein levels and cortisol response to dexamethasone and psychological stress tests. Therefore, it is hypothesized that the FKBP5 polymorphism affects personality traits. In the present study, we studied the association between this polymorphism and personality traits in 826 Japanese healthy subjects. Personality traits were assessed by the Temperament and Character Inventory (TCI), and the FKBP5 genotype was detected by a real-time PCR and cycling probe technology for SNP typing. In total subjects, the group with the T allele predictive of impaired negative feedback regulation of the HPA axis had higher scores of harm avoidance (HA) (p = 0.043) and lower scores of cooperativeness (CO) (p = 0.019) compared to that without the T allele. The T allele was associated with higher scores of HA in females (p = 0.020) and lower scores of CO in males (p = 0.015). The present study thus suggests that the FKBP5 polymorphism affects HA and CO in healthy subjects, with gender specificity.     

Adrenocorticotropin responses to interpersonal stress: effects of overt anger expression style and defensiveness.

This study evaluated the influence of overt anger expression style and defensiveness on the hypothalamic-pituitary-adrenocortical (HPA) responses to acute psychological stress. These personality traits are thought to modulate the stress cardiovascular response and influence disease risk, however, little is known about their influence on HPA responses. Forty-six young, healthy male volunteers worked on counterbalanced extended public-speaking and mental arithmetic. The sample was dichotomitized into groups low vs. high in anger-out, using Spielberger's Anger-Expression Inventory, and in defensiveness, using the Marlowe-Crown Social Desirability Scale. Serum cortisol and adrenocorticotropic hormone (ACTH) concentrations were measured before and after performing each task. Heart rate (HR) and blood pressures (BP) were obtained continuously in 2-min intervals before, during and after the tasks. Public speaking produced greater adrenocortical and cardiovascular stress responses than mental arithmetic, and the greatest increases in ACTH occurred in subjects high in anger-out and defensiveness. These preliminary findings provide evidence that a mismatch between traits of preferred anger expression style and defensive style produces pronounced adrenocorticotropic responses during socially salient stress.     

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.     

Exploring the relationship between personality and regional brain volume in healthy aging

Aging is characterized by a reduction in regional brain volumes, particularly in prefrontal and medial temporal regions. Recent evidence suggests that personality may be related to neuroanatomical integrity. The present investigation explored whether the three targeted personality traits of neuroticism, conscientiousness, and extraversion moderated cross-sectional age-related decline in measures of neural integrity. Estimates of the personality traits and volumes of cerebral gray and white matter, prefrontal and medial temporal regions were obtained in a sample of 79 healthy adults aged 44–88. Higher neuroticism was associated with smaller regional volumes and greater decreases in volume with increasing age. Higher conscientiousness was related to larger regional volumes and less decline with advancing age. These results suggest that personality may not only relate to, but may also moderate age-related cross-sectional decline in prefrontal and medial temporal regions.     

Positive illusions and its association with cardiovascular functions

The relationship between positive illusions (or self-enhancement) and cardiovascular functions was investigated using Asian samples in two studies. In phase 1 of Study 1, a generalized self-enhancement index was created for 241 participants using a paired word association memory task, a facial emotion recognition task, and a reading test. 122 participants subsequently volunteered for a second phase in this study where their ambulatory cardiovascular functions were measured throughout a single waking day. In Study 2, a priming procedure experimentally induced self-enhancement (n = 35) and self-effacement (n = 37) and the participants' cardiovascular arousal and perceived control for a mental arithmetic task were measured. Self-enhancement predicted lower cardiovascular functions for both studies. In Study 1, self-enhancement assessed at phase 2 was a significant predictor while self-enhancement measured at phase 1 was not. In Study 2, the relationship between self-enhancement and vascular reactivity was partially mediated by perceived control. The findings indicate that the relationship between self-enhancement and cardiovascular stress response, which has implications for cardiovascular health, (i) is relevant for Asian populations, (ii) is not just correlational but potentially causal, and (iii) is partly mediated by an increase in perceived control for vascular reactivity.     

Religious motivation and cardiovascular reactivity among middle aged adults: is being pro-religious really that good for you?

Religiousness has been observed to have a beneficial relationship with blood pressure, however, specific aspects of religiousness that interact with physiological mechanisms to influence this relationship are not known. This study explored laboratory cardiovascular reactivity (blood pressure, heart rate) to psychological stress among middle aged community dwelling individuals grouped by religious motivation (Intrinsic, Pro-religious, Non-religious). Measures of personality, cynical hostility, aggression, sense of coherence, and compassion were administered. Results indicated that the Pro-religious group demonstrated dampened reactivity compared to the other research groups. However, the Pro-religious also demonstrated a less positive psychological profile (e.g., greater cynicism, aggression, and neuroticism; less compassion and sense of coherence) and poorer self-reported health compared with the Intrinsic group and behavioral observations demonstrated that the Pro-religious were unreliable in keeping appointments and appeared rushed during the experiment. These findings indicate a complicated interface between personality, coping, and religious motivation in response to stressors and emphasize the need for naturalistic and longitudinal investigations of individuals who vary in terms of religious motivation.     

Affective and neuroendocrine stress reactivity to an academic examination: influence of the 5-HTTLPR genotype and trait neuroticism

The current study examined the singular and interactive effects of the 5-HTTLPR genotype and trait neuroticism on affective and physiological stress responses to an academic examination in healthy undergraduate students. From 771 students, 46 short/short (S/S)-allele carriers and 48 long/long (L/L)-allele carriers with the lowest and the highest neuroticism scores (80 females, 14 males; mean age ± SD: 20.3 ± 1.7 years) were selected. Salivary cortisol concentrations, mood and perceived stress were assessed before and after a 2-h written examination and compared with a control day. Negative mood, perceived stress and cortisol significantly increased during the examination compared to the control day. Negative stress effects on mood and perceived stress were significantly larger for S/S-allele carriers compared to L/L-allele carriers, regardless of trait neuroticism. Since vulnerability to real-life stressors is an important risk factor for depression pathogenesis, this may be a mediating factor making S/S-allele carriers more susceptible for depression symptoms.     

Psychometric assessment of female overactive bladder syndrome and antimuscarinics-related effects

Objectives

To investigate the characteristics of psychological distress (PD), personality traits, and family support in women with overactive bladder syndrome (OAB), and the effects of antimuscarinic treatment.

Study design

Women with and without OAB (age- and body mass index [BMI]-matched control group) were prospectively enrolled; they recorded bladder diaries, underwent urodynamic studies, and completed PD, personality traits, and filled family support questionnaires before and after antimuscarinic treatment. OAB women underwent treatment with tolterodine or solifenacin for 12 weeks. The control group completed questionnaires.

Main outcome measures

The differences in PD, personality traits, and family support scores between both groups, and the changes after antimuscarinic treatment in OAB women.

Results

Eighty-five women with OAB (tolterodine, n = 42; solifenacin, n = 43) and 65 without OAB completed the studies. Linear regression analysis with age and BMI adjustment revealed: coefficients of OAB were significant (all P < 0.05) for somatic complaints (mean: 0.87 vs. 0.63, coefficient = 0.21), obsessive–compulsive symptoms (0.69 vs. 0.44, coefficient = 0.25), anxiety symptoms (0.42 vs. 0.27, coefficient = 0.14), General Symptom Index (GSI, 0.48 vs. 0.33, coefficient = 0.14), neuroticism (9.23 vs. 5.17, coefficient = 3.73), and extroversion–introversion (13.64 vs. 15.25, coefficient = −1.73). Anxiety symptoms (0.42 vs. 0.36) and GSI (0.48 vs. 0.39) improved after antimuscarinics (all P < 0.05). High Overactive Bladder Symptom Score questionnaire score (coefficient = −0.39), low hostility score (coefficient = 2.11), and high additional symptoms score (coefficient = −1.46) were associated with good therapeutic effect (all P < 0.05).

Conclusions

OAB women experience more PD, neuroticism, and introversion than asymptomatic women, and antimuscarinics could improve PD.