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ObjectiveCardiovascular disease is the leading cause of death in kidney transplant recipients (KTRs), yet incompletely accountable by traditional risk factors. Inflammation is an unconventional cardiovascular risk factor, with gut-derived endotoxemia potentially driving inflammation and endothelial disease. Comparable data are lacking in kidney transplantation. This study investigated the associations of endotoxemia with inflammation, endothelial activation, and 5-year cardiovascular events in KTRs. Determinants of endotoxemia were also explored.Design and MethodsThis is a single-center cross-sectional study with prospective follow-up from a prevalent cohort of 128 KTRs.Main Outcome MeasuresDemographic, nutritional and clinical predictors of inflammation (high-sensitivity C-reactive protein [hsCRP]), endothelial activation (sE-selectin), and endotoxemia (endotoxin) were assessed. Follow-up data on 5-year cardiovascular event rates were collected.ResultsEndotoxemia (P = .03), reduced 25-hydroxyvitamin D (P = .04), high fructose intake (P P P = .002) were independently associated with elevated hsCRP. In turn, endotoxemia (P = .007) and increasing hsCRP (P = .02) were both independently associated with raised sE-selectin. Furthermore, endotoxemia predicted increased cardiovascular event rate (P = .02), independent of hsCRP and a global measure of cardiovascular risk estimated by a validated algorithm of 7-year risk for major adverse cardiac events in kidney transplantation. Determinants of endotoxemia included reduced 25-hydroxyvitamin D (P P P = .01), and abdominal obesity (P = .01).ConclusionsEndotoxemia in KTRs contributes to inflammation, endothelial activation, and increased cardiovascular events. This study highlights the clinical relevance of endotoxemia in KTRs, suggesting future interventional targets.

Correlation dimension (D2), a measure of heart rate (HR) complexity, has been shown to decrease in response to acute mental stress and relate to adverse cardiovascular health. However, the relationship between stress-induced changes in D2 and HR has yet to be established. The present studies aimed to assess this relationship systematically while controlling for changes in respiration and autonomic activity. In Study 1 (N = 25) D2 decreased during stress and predicted HR reactivity even after adjusting for changes in respiration rate, and cardiac vagal tone. This result was replicated in Study 2 (N = 162) and extended by including a measure of cardiac sympathetic activity; correlation dimension remained an independent predictor of HR reactivity in a hierarchical linear model containing measures of cardiac parasympathetic and sympathetic activity and their interaction. These results suggest that correlation dimension may provide additional information regarding cardiac stress reactivity above that provided by traditional measures of cardiac autonomic function.

Bereavement, the loss of someone close, is frequently followed by grief and can have serious implications for physical and mental health, from the increased symptoms of depression and anxiety, sleep disturbances and indigestion, and more serious physical health consequences such as cardiovascular and immune related illness. Another key factor associated with a deterioration of the body’s defence mechanisms, such as the immune system, is ageing. This review has as its focus the combined effects of bereavement and ageing on immune function. First, the relationship between bereavement and increased mortality is examined, followed by its link to various physical and mental health morbidities. Second, the effects of ageing per se on immune functions are considered. Finally, the joint impact of both ageing and bereavement are discussed, focussing on recent studies of immune function after bereavement in young and older adults.

Background and aims Problematic Internet use and excessive alcohol consumption have been associated with a host of maladaptive outcomes. Further, low (blunted) cardiovascular and stress hormone (e.g. cortisol) reactions to acute psychological stress are a feature of individuals with a range of adverse health and behavioural characteristics, including dependencies such as tobacco and alcohol addiction. The present study extended this research by examining whether behavioural dependencies, namely problematic Internet use, excessive alcohol consumption, and their comorbidity would also be associated with blunted stress reactivity Methods A large sample of university students (N = 2313) were screened using Internet and alcohol dependency questionnaires to select four groups for laboratory testing: comorbid Internet and alcohol dependence (N = 17), Internet dependence (N = 17), alcohol dependence (N = 28), and non-dependent controls (N = 26). Cardiovascular activity and salivary cortisol were measured at rest and in response to a psychological stress protocol comprising of mental arithmetic and public speaking tasks. Results Neither problematic Internet behaviour nor excessive alcohol consumption, either individually or in combination, were associated with blunted cardiovascular or cortisol stress reactions. Discussion It is possible that problematic Internet behaviour and excessive alcohol consumption in a student population were not related to physiological reactivity as they may not reflect ingrained addictions but rather an impulse control disorder and binging tendency. Conclusions The present results serve to indicate some of the limits of the developing hypothesis that blunted stress reactivity is a peripheral marker of the central motivational dysregulation in the brain underpinning a wide range of health and behavioural problems.

A number of studies have now examined the association between smoking and the magnitude of physiological reactions to acute psychological stress. However, no large-scale study has demonstrated this association incorporating neuroendocrine in addition to cardiovascular reactions to stress. The present study compared neuroendocrine and cardiovascular reactions to acute stress exposure in current smokers, ex-smokers, and those who had never smoked in a large community sample. Salivary cortisol, systolic and diastolic blood pressure, heart rate and frequency components of systolic blood pressure and heart rate variability were measured at rest and during exposure to a battery of three standardized stress tasks in 480 male and female participants from the Dutch Famine Birth Cohort Study. Current smokers had significantly lower cortisol, systolic and diastolic blood pressure, and heart rate reactions to stress. They also exhibited smaller changes in the low frequency band of blood pressure variability compared to ex- and never smokers. There were no group differences in stress related changes in overall heart rate variability as measured by the root mean square of successive interbeat interval differences or in the high frequency band of heart rate variability. In all cases, effects remained significant following statistical adjustment for a host of variables likely to be associated with reactivity and/or smoking. In secondary analyses, there were no significant associations between lifetime cigarette consumption or current consumption and stress reactivity. In conclusion, compared to non-smokers and ex-smokers, current smokers exhibited attenuated neuroendocrine and cardiovascular reactions to acute psychological stress. Among smokers and ex-smokers, there is no evidence that lifetime exposure was associated with physiological reactions to acute stress, nor that current levels of cigarette consumption were associated with reactivity. It is possible, then, that attenuated stress reactivity may be a marker for an increased susceptibility to take up and/or maintain smoking behaviour once initiated.

In this chapter, we discuss how social and biological studies of ageing can converge to provide a meaningful framework for progress in both understanding ageing and dealing with it in a positive manner. We start by discussing the meaning of the term 'ageing' and how it is in part defined by social context, and then, how psychosocial factors have an impact on both perception and the biological reality of ageing. From a theoretical perspective, we assess how ageing might have evolved, and how it is measured. The biological impacts of ageing are then described, moving from individual cells through tissues to major organ systems (immune, cardiovascular and nervous systems) (see Figure 2.1). What causes individual cells of the body to age is dealt with at both a cellular and molecular level, and we further discuss how studies of both extremely long-lived and short-lived humans have contributed significantly not only to our understanding of the biological processes of ageing, but also to the possibility of developing therapies to deal with the problems that cause greatest loss of quality of life in older age. We end by assessing the ethical case for intervening in those biological processes underpinning the development of those illnesses that so undermine health in later life.

A series of meta‐analyses was undertaken to determine the contributions of sympathetic and parasympathetic activation to cardiovascular stress reactivity. A literature search yielded 186 studies of sufficient quality that measured indices of sympathetic (n = 113) and/or parasympathetic activity (n = 73). A range of psychological stressors perturbed blood pressure and heart rate. There were comparable aggregate effects for sympathetic activation, as indexed by increased plasma epinephrine and norepinephrine, and shortened pre‐ejection period and parasympathetic deactivation, as indexed by heart rate variability measures. Effect sizes varied with stress task, sex, and age. In contrast to alpha‐adrenergic blockade, beta‐blockade attenuated cardiovascular reactivity. Cardiovascular reactivity to acute psychological stress would appear to reflect both beta‐adrenergic activation and vagal withdrawal to a largely equal extent.

Ageing is accompanied by reduced functioning of the immune system, termed immunesenescence which is associated with increased risk of infection and mortality. However the immune system does not operate in isolation and can be modified by many environmental factors, including stress. In this study we determined whether physical stress (hip fracture) and psychological distress (depressive symptoms) had additive effects upon the aged immune system, specifically on monocyte numbers and function. We assessed immune function in 101 hip fracture patients (81 female) 6 weeks and 6 months after injury and 43 healthy age matched controls (28 females). Thirty-eight of the hip fracture group were found to be depressed at the 6 week sampling. No differences in peripheral monocyte count, distribution of monocyte subsets or TNFα secretion were observed between hip fracture patients and healthy controls. However we observed significantly reduced superoxide production in response to Escherichia coli in the monocytes of hip fracture patients who developed depressive symptoms compared with non-depressed hip fracture patients (p = 0.002) or healthy controls (p = 0.008) 6 weeks after the fracture which remained decreased 6 months following injury. In previous studies we have shown an effect of depression on neutrophil superoxide generation in hip fracture patients, suggesting a particular susceptibility of this aspect of immune cell function to psychological stress.

Objective This analysis examines whether or not younger caregivers, parents of children with developmental disabilities, differed from controls in terms of cytomegalovirus (CMV) seropositivity and CMV-specific antibody titre. Secondly, it examined whether any particular socio-demographics, health behaviours, or psychological/caregiving variables were associated with a higher CMV antibody titre among caregivers. Design Young caregivers and age- and sex-matched controls were compared with respect to their reported health behaviour and psychosocial status as well as latent virus control. Methods One hundred and seventeen parents of children with developmental disabilities and 52 control parents completed standard measures of health behaviours, socio-demographics, perceived stress, depression and anxiety, caregiver burden, child problem behaviours. They also provided a blood sample assayed for the presence of CMV-specific antibody. Results Caregivers were no more likely to be CMV positive than controls and did not have higher antibody titres against CMV. In addition, there was no association between CMV antibody titre in seropositive caregivers and any of the psychological/caregiving variables. However, higher CMV antibody titres were significantly associated with a higher BMI, lower exercise levels, smoking, and lower fruit and vegetable and fat intake among seropositive caregivers. Conclusions These data suggest that in the absence of immunosenescence, the chronic stress of caregiving is not sufficient to compromise the immune response to persistent CMV infection. However, an indirect mechanism to poorer health in caregivers might be via adoption of disadvantageous health behaviours in response to stress. Statement of contribution What is already known on this subject? Older caregivers of spouses with dementia show a poorer immune response against latent viruses when compared to age- and sex-matched controls. Younger parental caregivers of children with developmental disabilities show a poorer antibody response to vaccination. What does this study add? The study showed no association between caregiving stress and CMV antibody titre in young caregivers. There were higher CMV antibody titres in the caregivers who engage in unhealthy behaviours.

Life expectancy is increasing, but the time spent in good health (health-span) is not keeping pace, with implications for health, social care, and pensions resulting in estimated costs more than doubling by 2050. Thus, understanding the many factors that contribute to healthy ageing versus frailty, and potential things we can do to promote healthy ageing is important. For example, how does stress, being physically inactive and poor dietary practices affect our body, leading to unhealthy ageing? As part of the 2015 Pint of Science series, researchers interested in brain health, muscle function and the immune system from the School of Sport, Exercise and Rehabilitation Sciences at the University of Birmingham, UK discussed the effects that ageing itself and stress, physical activity and nutrition can have on our health and wellbeing. The objective of our presentation was to question the lifestyle that we lead and discuss realistic alternatives to incorporate healthy activity, such as exercise, into our lifestyles to improve our healthy ageing. Here, we summarise this presentation and illustrate the effectiveness of physical activity for ageing healthily. Commentary Public health interventions along with health care and education improvements over several decades have led to an increase in life expectancy and global population ageing (1). However, an inactive lifestyle in old age is one of the main causes of muscle wasting, which increases the risk of falls, fractures and disability and reduces quality of life (2-4). If we do not find a way to prevent muscle wasting in old age, we will be faced with an unprecedented number of frail/disabled older individuals in our society. Further, age is one of the most important risk factors for brain diseases such as dementia and stroke (5), but even with natural healthy ageing, brain structure and function is altered, thus our ageing (and sedentary) population presents a looming economic and social issue. Urgent implementation of effective countermeasures is critical to fully prepare for the challenges of the world's changing demographics and create an equitable, affordable and sustainable ageing society for the future. Major efforts need to focus on 'prevention', with emphasis on modifiable risk factors such as engagement in physical activity right across the life span. Engaging in regular physical activity has clear benefits for our health, preventing and treating diseases that drive poor quality of life, thereby reducing the incidence of morbidity (for example, depression, dementia, cardiovascular and cerebrovascular disease, type 2 diabetes, and some cancers) and premature mortality. Thus, exercise has a significant role to play in both the prevention and treatment of disease as well as minimise the effects of ageing. However, despite its clear benefits, 80-100% of us (depending on age and sex) do not meet public health recommendations for physical activity [z.e.,[greater than or equal to] 30 min of moderate-intensity exercise on at least 5 days of the week ([greater than or equal to] 150 min [wk.sup.-1]), or 20 min of vigorous-intensity aerobic exercise training on at least 3 days of the week ([greater than or equal to] 75 min [wk.sup.-1]) (6,7)]. In fact, 'physical inactivity' has now become a top 10 killer in our society (8). A busy lifestyle and the associated 'lack of time' is frequently cited as a common barrier to engaging in regular exercise (9); however, in addition to this perceived barrier to being active, this busyness also has direct negative implications for our health and well-being. Research has demonstrated that psychological stress can make us ill and contribute to the development of a range of diseases. For example, long-term ongoing stress or distress like care giving, bereavement, or depression can actually worsen how our bodies' immune system functions, making us more susceptible to infections, and less likely to recover quickly from infections and wounds or surgery (see refs 10-14). …

Background: The prevalence and consequences of hypervolemia in kidney transplant recipients (KTRs) have not been investigated. Specifically, its impact on blood pressure (BP) and relationship with N-terminal fragment of prohormone B-type natriuretic peptide (NT-proBNP) are unknown. The objectives of this study were to establish the prevalence of hypervolemia among clinically stable KTRs, investigate the predictors of posttransplant hypervolemia, assess its impact on blood pressure, and determine its relationship with NT-proBNP.Methods: This single-center cross-sectional study enrolled 123 clinically stable KTRs. Extracellular volume status was determined by multifrequency bioimpedance analysis. Mild and severe hypervolemia were defined as percentage volume expansion of greater than 7% and greater than 15%, respectively. Systolic BP (SBP) and diastolic BP (DBP) were measured, with mean arterial pressure (MAP) calculated. Serum NT-proBNP was quantified using a noncompetitive immunoluminometric assay. Potential demographic, nutritional, and clinical predictors of extracellular volume status, BP, and NT-proBNP levels were assessed.Results: Hypervolemia was present in 30% of KTRs, with 5% classified as severe hypervolemia. Significant predictors of volume expansion were increased sodium intake, advancing age, and reduced fat mass (PConclusions: Hypervolemia is unexpectedly common among clinically stable KTRs. It is closely associated with elevated BP. The relationship with increased sodium intake signals potential therapeutic focus. Further study is warranted to prospectively investigate objective measures of extracellular volume status among KTRs.

Highlight • Depressive symptoms are a major driver of reduced immunity after hip fracture., Hip fracture is a common trauma in older adults with a high incidence of depression, which relates to poorer prognosis including increased risk of infection. Ageing is accompanied by reduced immunity, termed immunesenescence, resulting in increased susceptibility to infection. We examined whether physical trauma (hip fracture) and psychological distress (depressive symptoms) had additive effects upon the aged immune system that might contribute to poor outcomes after injury. Neutrophil function was assessed in 101 hip fracture patients (81 female) 6 weeks and 6 months after injury and 43 healthy age-matched controls (28 female). Thirty eight fracture patients had depressive symptoms at 6 weeks. No difference in neutrophil phagocytosis of Escherichia coli was observed between controls and hip fracture patients, but superoxide production was significantly reduced in hip fracture patients with depressive symptoms compared with patients without symptoms (p = .001) or controls (p = .004) at 6 weeks. Superoxide production improved 6 months following fracture to the level seen in controls. We detected elevated serum cortisol, reduced dehydroepiandrosterone sulphate (DHEAS) and an increased cortisol:DHEAS ratio in fracture patients with depressive symptoms compared with patients without depressive symptoms or controls at 6 weeks and 6 months after injury. Serum IL6, TNFα and IL10 were higher among patients with depressive symptoms at 6 weeks. The cortisol:DHEAS ratio and IL6 levels related to depressive symptom scores but not to neutrophil function. In conclusion, depressive symptoms related to poorer neutrophil function after hip fracture, but this was not driven by changes in stress hormone or cytokine levels.

The present study compared neural activity in participants with blunted (N = 9) or exaggerated (N = 8) cardiac stress reactions. Neural activity was recorded with fMRI while participants performed a validated stress task and control task. Exaggerated reactors exhibited significant increases in heart rate from control to stress task, whereas blunted reactors had no change in heart rate. Blunted reactors also had reduced activation in the anterior midcingulate cortex and insula compared to exaggerated reactors during the stress condition, and a greater deactivation in the amygdala and posterior cingulate. The biological differences between groups in response to the stress task could not be explained by subjective measures of engagement, stressfulness, or difficulty. This study supports the notion that blunted peripheral physiological stress reactivity may be a marker of a corresponding under-recruitment of brain systems during behavioral states requiring motivated action.

Ageing is a physiological process that is part of normal development (Cutler, 1991). However, the stress response in humans, although an adaptive mechanism initially, has the potential to be chronic and detrimental to the organism if too large and/ or prolonged (Sapolsky, 2007). This particularly appears to be the case later in the lifespan; in fact some of the changes in older age mirror the chronic effects of stress on several of the body’s biological systems. This chapter will mainly focus on the impact of stress on the immune system and the implications for resilience in older age, as stress effects on all bodily systems are beyond the scope of one chapter. Further, the immune system undergoes several changes with ageing, resulting in increased susceptibility to infectious and autoimmune diseases and cancer, all of which are also influenced by stress.

Recent evidence demonstrates that individuals with low heart rate (HR) reactions to acute psychological stress are more likely to be obese or smokers. Smoking and obesity are established risk factors for increased carotid intima-media thickness (IMT). The aim of this study was to examine the potential pathways linking intima-media thickness, smoking, body mass index (BMI), and HR stress reactivity. A total of 552 participants, 47.6% male, M (SD) age = 58.3 (0.94) years, were exposed to three psychological stress tasks (Stroop, mirror drawing, and speech) preceded by a resting baseline period; HR was recorded throughout. HR reactivity was calculated as the average response across the three tasks minus average baseline HR. Smoking status, BMI, and IMT were determined by trained personnel. Controlling for important covariates (e.g., socioeconomic status), structural equation modeling revealed that BMI and smoking mediated the negative relationship between HR reactivity and IMT. The hypothesized model demonstrated a good overall fit to the data, χ(2) (8) = 0.692, p = .403; CFI = 1.00; TLI = 1.00 SRMR = .01; RMSEA

Exaggerated cardiovascular reactions to acute psychological stress may be involved in the etiology of cardiovascular pathology. The present analysis examined the association between the magnitude of systolic and diastolic blood pressure reactions to stress and cardiovascular disease mortality. Participants were 431 (229 women) from the West of Scotland Twenty-07 Study, aged 63 years at the time of stress testing, where blood pressure was measured during resting baseline and mental arithmetic stress. Participants' vital status was tracked for the next 16 years, during which time 38 had died of cardiovascular disease. Both systolic and diastolic blood pressure reactions were positively associated with cardiovascular disease mortality. This association could reflect the long-term erosive effects of exaggerated reactivity on the vasculature as well as its short-term capacity to trigger acute cardiovascular events.

Aging is accompanied by the development of low-grade systemic inflammation, termed 'inflammaging', characterized by raised serum C-reactive protein (CRP) and pro-inflammatory cytokines. Importantly, inflammaging is implicated in the pathogenesis of several of the major age-related diseases including cardiovascular disease, type 2 diabetes, and dementia and is associated with increased mortality. The incidence of infection with the persistent herpes virus cytomegalovirus (CMV) also increases with age. Cross-sectional studies have proposed CMV infection as a significant driver of inflammaging, but a definitive case for CMV as a causative agent in inflammaging has not yet been made. We studied longitudinally 249 subjects (153 men, 96 women) who participated in the Hertfordshire Ageing Study at baseline (1993/5, mean age 67·5 years) and at 10 year follow-up. At both times, anthropometric measurements were made and subjects provided blood samples for analysis of inflammatory status and CMV seropositivity. In the cohort as a whole, serum CRP (P < 0·02) and pro-inflammatory cytokines TNFα (P < 0·001) and IL-6 (P < 0·001) were increased between baseline and follow-up sampling whereas levels of the anti-inflammatory cytokine IL-10 were decreased (P < 0·001). These changes to cytokine status over time occurred equally in the 60% of subjects who were seropositive for CMV at baseline and follow-up, the 8% who were CMV negative at baseline but who became CMV positive by the 10 year follow-up, and also in the 32% who were CMV seronegative throughout. We conclude that CMV infection is not a primary causative factor in the age-related increase in systemic inflammation.

Background/Study Context: The cortisol diurnal rhythm has previously been examined in relation to age and health behaviors. However, less is known about the relationship between multiple health behaviors and diurnal cortisol in the context of aging, where it is possible that the impact of health behaviors on cortisol varies as a function of age. This study compared the awakening response and diurnal rhythm of cortisol in young versus older adults in relation to health behaviors. Methods: Twenty-four young students (aged 18–22) and 48 community-dwelling older adults (aged 65–88) completed an assessment of health behaviors (exercise, smoking, sleep, diet, alcohol) over the past year. Salivary cortisol was measured over the course of 1 day: immediately upon awakening, 30 min later, and then 3, 6, 9, and 12 h post awakening. Repeated measures/univariate analysis of variance (ANOVA) was used to test main effects of age and health behaviors, and any interaction effects in relation to diurnal cortisol. Results: Older adults displayed significantly reduced cortisol upon awakening, a lower cortisol awakening response, and a flatter diurnal profile represented by a reduced area under the curve and cortisol slope. There was also a significant interaction of age, cortisol, and diet; younger adults with a higher fat and lower fruit and vegetable intake exhibited the flattened diurnal cortisol phenotype of the older adults. Conclusion: These findings suggest that the diurnal rhythm and awakening response of salivary cortisol is significantly reduced in older adults and that variations in the cortisol diurnal rhythm of younger adults are associated with dietary factors. Younger adults with a poor quality of food intake may be vulnerable to a reduction in the amplitude of the cortisol diurnal profile and this may have implications for other aspects of health.

The present study examined the relationship between ageing, physical function and the diurnal rhythms of cortisol and dehydroepiandrosterone (DHEA). Participants were 36 community dwelling older adults aged between 65-86 years old. Salivary cortisol and DHEA were measured over the course of one day: immediately upon awakening, 30 min later, and then 3 h, 6 h, 9 h and 12 h post-awakening. Participants completed the Nottingham extended activities of daily living index, the Berg Balance Scale and their handgrip strength was assessed. Older participants had a significantly higher cortisol area under the curve (AUC), lower overall DHEA levels, lower DHEA AUC, a decreased diurnal slope of decline and increased cortisol:DHEA ratio. Lower diurnal cortisol levels were associated with poorer performance on the Berg Balance Scale and lower handgrip strength, and those with a flattened DHEA diurnal profile reported less independence in carrying out daily tasks. These associations withstood adjustment for age. In conclusion, this study suggests an association between cortisol, DHEA, ageing and physical function.

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 five 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.

Background: There is no clear consensus in the few studies to have explored the relationship between major mental health disorders and lung function. The present study examined the cross-sectional associations of generalized anxiety disorder (GAD) and major depressive disorder (MDD) with lung function in a large study of male US veterans. Methods: Participants (N = 4256) were drawn from the Vietnam Experience Study. From military files, telephone interview, and a medical examination, anthropometric, socio-demographic, and health data were collected. One-year prevalence of GAD and MDD was determined using DSM-III criteria. Forced expiratory volume in one second (FEV1) was measured by spirometry. Results: In models that adjusted for age and height, both GAD, p < .001, and MDD, p = .004, were associated with lower FEV1. In models additionally adjusting for weight, place of service, ethnicity, marriage, smoking, alcohol consumption, income, education, and major illness, GAD was still associated with poorer lung function, p = .01, whereas MDD was not, p = .18. Conclusions: Depression has very much been the focus of studies on mental health and physical health status. The current findings suggest that future research should perhaps pay equal attention to GAD.

Interdisciplinary work between psychologists and immunologists has shown that factors like stress could be the trigger that lead to the development of a bout of illness. By studying the response to vaccination, we can examine immune function in the context of the rest of the body in a clinically meaningful way. This technique has been used to demonstrate consistent relationships between stress and the response to influenza vaccination and other vaccines, as well as links between other factors, such as social support and personality, and vaccination-induced protection against disease. There are several ways the vaccination response can be used to understand more about how stress influences immunity. In addition, specific types of stress and other factors that influence our immune response appear to differ across different populations, which emphasises the importance of taking a life course approach to studying these relationships.

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.

Bereavement is a common life event for older adults and is associated with increased risk of morbidity and mortality, though the underlying reasons for this link are poorly understood. Although physical and emotional stressors and ageing are known to suppress immunity, few studies have explored the impact of bereavement upon immunity in the older population. We therefore hypothesised that the emotional stress of bereavement would suppress immune function, specifically neutrophil bactericidal activity, in older adults. A between-subjects design was used to examine the effect of recent bereavement (2 months) on neutrophil function in elders. Participants were 24 bereaved and 24 age- and sex-matched non-bereaved controls all aged 65+ years. Neutrophil phagocytosis of Escherichia coli (E. coli) and stimulated superoxide production were assessed. Cortisol and dehydroepiandrosterone-sulphate (DHEAS) levels were determined in serum to assess potential mechanisms. Depressive and anxiety symptoms were measured by questionnaire. Neutrophil superoxide production was significantly reduced among the bereaved when challenged with E. coli (p=0.05), or phorbol 12-myristate 13-acetate (p=0.009). Further, the bereaved group had a significantly higher cortisol:DHEAS ratio compared to controls (p=0.03). There was no difference in neutrophil phagocytosis between the two groups. The psychological questionnaire results showed that the bereaved had significantly greater depressive and anxiety symptoms than the non-bereaved. The emotional stress of bereavement is associated with suppressed neutrophil superoxide production and with a raised cortisol:DHEAS ratio. The stress of bereavement exaggerates the age-related decline in HPA axis and combines with immune ageing to further suppress immune function, which may help to the explain increased risk of infection in bereaved older adults.

Cross-sectional associations between white blood cell (WBC) count, lymphocyte and granulocyte numbers, and carotid intima-media thickness (IMT) and brachial-ankle pulse wave velocity (PWV) were examined in a novel older Chinese community sample. A total of 817 men and 760 women from a sub-study of the Guangzhou Biobank Cohort Study had a full blood count measured by an automated hematology analyzer, carotid IMT by B-mode ultrasonography and brachial-ankle PWV by a non-invasive automatic waveform analyzer. Following adjustment for confounders, WBC count (β=0.07, P

Objectives: The aim of these analyses was to examine the association of cortisol, dehydroepi- androsterone sulphate (DHEAS), and the cortisol:DHEAS ratio with the diagnoses of major depressive disorder (MDD), generalised anxiety disorder (GAD), and their comorbidity. Design: This was a cross-sectional study. Methods: Participants were 4256 Vietnam era US army veterans. From military service files, telephone interviews, and a medical examination, occupational, socio-demographic, and health data were collected. One-year prevalence of MDD and GAD was determined through a diagnostic interview schedule based on the DSM-IV criteria. Contemporary morning fasted cortisol and DHEAS concentrations were determined. Analyses of covariance were run, first with adjustment for age and then additionally adjusting for a range of candidate confounders. Results: In fully adjusted analyses, there was evidence of lower basal cortisol levels in individuals with MDD and co-morbid MDD and GAD than those with GAD alone or no diagnosis. Conclusion: This suggests that MDD and its comorbidity can also be characterised by low as well as high cortisol levels. A profitable line of future research might be to examine cortisol and DHEAS levels in more representative samples including older participants and women with and without MDD, GAD, and other psychiatric diagnoses.

The reactivity hypothesis implicates exaggerated cardiovascular reactions to acute psychological stress in the development of hypertension and other cardiovascular disease outcomes. However, exaggerated cardiovascular reactivity has also been suggested as a mediator between a variety of psychosocial and behavioral risk factors and cardiovascular disease. Recent data analyses from the West of Scotland Twenty-07 study and our own group are discussed together, to show that blunted as well as exaggerated cardiovascular reactivity to stress may be associated with negative health outcomes. Blood pressure and heart rate were assessed at rest and during an acute mental arithmetic stress task. We show that depression and obesity are associated with blunted rather than exaggerated reactivity. These seemingly paradoxical results are discussed in terms of implications for the reactivity hypothesis.

Few studies have examined the association between cognitive ability and cardiovascular reactivity, although both have been implicated in later cardiovascular disease. We studied the relationship between cognitive ability, assessed using the Alice Heim-4 test of general intelligence, simple reaction time, and subsequent cardiovascular reactivity in 409 55-year-olds. Blood pressure and heart rate reactions to an acute mental arithmetic task were measured 7 years after cognitive assessment. In regression models that adjusted for baseline cardiovascular activity, socio-demographics, body mass index, medication status, and stress task performance, cognitive ability and reaction time were associated with future cardiac reactivity. Low reactivity was characteristic of those with relatively low cognitive ability. The results are consistent with the notion that high reactivity may not always be a maladaptive response.

We recently reported a cross-sectional negative relationship between cardiovascular reactivity and depressive symptoms. The present analyses examined the prospective association between reactivity and symptoms of depression 5 years later. At the earlier time point, depressive symptoms, measured using the Hospital Anxiety and Depression Scale (HADS), and cardiovascular reactions to a standard mental stress were measured in 1,608 adults comprising three distinct age cohorts: 24-, 44-, and 63-year-olds. Depression was reassessed using the HADS 5 years later. Heart rate reactions to acute psychological stress were negatively associated with subsequent depressive symptoms; the lower the reactivity the higher the depression scores. This association withstood adjustment for symptom scores at the earlier time point and for sociodemographic factors and medication status. The mechanisms underlying this prospective relationship remain to be determined.

Objective: To examine the effects of an acute laboratory psychological stress task on neutrophil function, specifically phagocytosis of Escherichia coli and stimulated superoxide production in human neutrophils. There is mounting evidence that acute stress is associated with short-term increases in a number of immune indices. Methods: Participants were 40 (n = 20 females) university students (mean age, 25.9 ± 4.56 years). Blood samples to determine neutrophil function by flow cytometry were taken at the end of resting baseline, during an acute stress task, and during recovery. The stress task was a 10-minute time-pressured mental arithmetic challenge with social evaluation. Results: There was an acute increase in phagocytic ability, \(\rho\) = .047, η2p = 0.076, and a reduction of superoxide production, p = .026, η2p = 0.101, associated with the stress task relative to baseline. Conclusion: These findings suggest that neutrophil bactericidal function may be sensitive to mental challenge tasks that provoke acute psychological stress. Further research is needed to replicate the observed psychological stress-induced changes in neutrophil function.

ObjectivesThe aim of the present analyses was to examine the association between cortisol, DHEA sulphate (DHEAS) and the cortisol:DHEAS ratio and mortality.DesignThis was a prospective cohort analysis.MethodsParticipants were 4255 Vietnam-era US army veterans. From military service files, telephone interviews and a medical examination, occupational, socio-demographic and health data were collected. Contemporary morning fasted cortisol and DHEAS concentrations were determined. Mortality was tracked over the subsequent 15 years. The outcomes were all-cause, cardiovascular disease, cancer, other medical mortality and external causes of death. Cox proportional hazard models were tested, initially with adjustment for age, and then with adjustment for a range of candidate confounders.ResultsIn general, cortisol concentrations did not show an association with all-cause or cause-specific mortality. However, in age-adjusted and fully adjusted analyses, DHEAS was negatively related to all-cause, all cancers and other medical mortality; high DHEAS concentrations were protective. The cortisol:DHEAS ratio was also associated with these outcomes in both age-adjusted and fully adjusted models; the higher the ratio, the greater the risk of death.ConclusionsDHEAS was negatively associated, and the ratio of cortisol to DHEAS was positively associated with all-cause, cancer and other medical cause mortality. Further experimental study is needed to elucidate the mechanisms involved in these relationships.

Few studies have explored the relationship between individual and combined multiple indicators of socioeconomic status across the life course and the metabolic syndrome, or attempted to understand the mechanisms underlying any associations. The present study examined the associations between 4 indicators of socioeconomic status, individually and in combination, and metabolic syndrome risk in a study of male US veterans and examined the influence of health behaviors, intelligence, and psychologic distress on these associations. Participants (N = 4253) were drawn from the Vietnam Experience Study. From military service files, telephone interviews, and a medical examination, occupational, sociodemographic, health behavior, intelligence, psychologic, and health data were collected. The 4 indices of socioeconomic status were as follows: education achieved, early adulthood income, household income in midlife, and occupational prestige in midlife. Metabolic syndrome was diagnosed from the following: body mass index, fasting blood glucose or a diagnosis of diabetes, blood pressure-a diagnosis of hypertension or taking antihypertensives, high-density lipoprotein cholesterol, and triglyceride levels. In models that adjusted for age, men in the lower 2 groups on the combined measure of socioeconomic status experienced a higher risk of metabolic syndrome. This association was accounted for mainly by education achieved, household income in midlife, and occupational prestige in midlife. Intelligence appeared to explain much of this association. Combined socioeconomic status measures across the life course were related to metabolic syndrome but in a threshold rather than dose-response manner. Intelligence appeared to mediate this relationship.

Objectives. Self-reported health has a well established relationship to later mortality, although the reasons are not entirely understood. This study examined the association of a similar self-reported measure of fitness with mortality and compared it to that of self-reported health. Design. The study had a prospective cohort design with multiple sampling points. Methods. Participants were 858 men and women from Glasgow and the surrounding area of Scotland, aged 59 when self-reported health and fitness data were first collected in 1991/92. They were re-interviewed at age 64 and 69 and mortality was tracked for 16.5 years in total. Hazard ratios for all cause mortality were estimated for those that reported poor health or poor fitness relative to others their age, taking into account a range of covariates, some of which were also time varying. Results. In both unadjusted and covariate adjusted models, self-reported fitness was at least as good a predictor of mortality as self-reported health. In a mutually adjusted model, both again emerged as significant predictors. Poor subjective health with poor subjective fitness appeared to be a particularly lethal combination. Conclusion. Both self-reported health and self-reported fitness were independent predictors of mortality. Where the objective assessment of aerobic fitness is not feasible, a simple measure of subjective fitness could prove a useful alternative.

Objective: to examine the cross-sectional associations between generalized anxiety disorder (GAD) and major depressive disorder (MDD), their comorbidity, and hypertension. Methods: participants (n = 4180) were drawn from a cohort of men who were members of the U.S. army during the Vietnam war era. Occupational, sociodemographic, and health data were collected from military service files, telephone interviews, and medical examinations. Hypertension status was defined by the presence of one of the following: self-reports at interview of either a physician-diagnosis or taking antihypertensive medication; or an average systolic blood pressure ?140 mm Hg or an average diastolic blood pressure ?90 mm Hg at the medical examination. One-year prevalence of GAD and MDD was determined, using Diagnostic and Statistical Manual of Mental Disorders, Third Edition criteria. Results: in separate regression models adjusting for age and then additionally for place of service, ethnicity, marital status, alcohol consumption, smoking, body mass index, household income, and education grade, both GAD and MDD were related positively to hypertension. In age-adjusted and fully adjusted models comparing comorbid GAD/MDD, GAD alone, MDD alone, and neither condition, comorbidity showed the strongest relationship with hypertension. Conclusion: depression has been the main focus for research on mental health and physical health outcomes. The present results suggest that future research should pay equal attention to GAD and, in particular, the comorbidity of GAD and MDD

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.

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 five 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 five 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.

How we react physiologically to stress has long been considered to have implications for our health. There is now persuasive evidence that individuals who show large cardiovascular reactions to stress are at increased risk of developing cardiovascular disease, particularly hypertension. By implication, low reactivity is protective or benign. However, there is recent evidence that low reactivity may predict elevated risk for a range of adverse health outcomes, such as depression, obesity, poor self-reported health and compromised immunity. In addition, low cortisol and cardiovascular reactivity may be a characteristic of individuals with addictions to tobacco and alcohol, as well as those at risk of addiction and those who relapse from abstinence. Our ideas about reactivity may have to be revised in the light of such findings.

Objective: To examine the relationship between cardiovascular activity in response to acute psychological stress and the antibody response to vaccination. Methods: Fifty-seven healthy participants were vaccinated with the trivalent influenza vaccine and meningococcal A+C polysaccharides. Antibody levels were measured at baseline and 5-weeks post-vaccination. Cardiovascular activity was measured at rest, during and following a mental arithmetic stress task in 54 participants. Results: Participants demonstrating a four-fold increase in antibody titre to the A/Panama and B/Shangdong influenza strains and to meningococcal A showed greater blood pressure reactions toward the end of the acute stress task. In addition, there was some evidence of delayed diastolic blood pressure recovery in those who were responders to A/Panama and B/Shangdong influenza strains. Conclusion: The present results suggest that heightened cardiovascular reactivity to stress and delayed recovery may not necessarily be detrimental to all aspects of health, and may be associated with an enhanced immune response to antigen challenge.

peer-reviewed In older populations, caregiving for a spouse with dementia has been associated with a poor antibody response to vaccination. The present study examined whether younger caregivers, specifically the parents of children with developmental disabilities, would also show a diminished antibody response to vaccination. At baseline assessment, 30 parents of children with developmental disabilities and 29 parents of typically developing children completed standard measures of depression, perceived stress, social support, caregiver burden, and child problem behaviours. They also provided a blood sample and were then vaccinated with a pneumococcal polysaccharide vaccine. Further blood samples were taken at 1- and 6-month follow-ups. Caregivers mounted a poorer antibody response to vaccination than control parents at both follow-ups. This effect withstood adjustment for a number of possible confounders and appeared to be, at least in part, mediated by child problem behaviours. The negative impact of caregiving on antibody response to vaccination is not restricted to older spousal caregivers, but is also evident in younger parents caring for children with developmental disabilities. The behavioural characteristics of the care recipients may be a key consideration in whether or not immunity is compromised in this context. ACCEPTED peer-reviewed

peer-reviewed Background: Exaggerated cardiovascular reactions to psychological stress are considered a risk factor for cardiovascular morbidity. Social support may reduce such risk by attenuating cardiovascular reactivity to stress. Purpose: To examine the effects of three independent social support variables and their interaction on cardiovascular reactivity to acute stress. The variables were stranger or friend presence; active supportive or passive presence, and male or female presence. Methods: Cardiovascular reactions to mental arithmetic stress were measured in 112 healthy young women tested in one of eight distinct independent conditions: active supportive male friend; active supportive female friend, passive male friend; passive female friend; active supportive male stranger; active supportive female stranger, passive male stranger; and passive female stranger. Results: Support from a friend rather than a stranger was associated with attenuated blood pressure reactivity, but only when the supporter was a male friend. Support from a male stranger or female friend was associated with augmented blood pressure reactivity. Conclusions: This interaction between the intimacy and sex of the supporter on cardiovascular reactivity extends the findings of previous laboratory studies of social support and can, to an extent, be interpreted in terms of Social Comparison Theory.