Thomas W. Kamarck - US grants

A growing body of evidence suggests that an individual's social network may be an important determinant of health and well-being -- for example, socially isolated individuals appear to be at greater risk for all causes of premature mortality, including mortality from cardiovascular disease. Preliminary evidence implicates excessive cardiovascular reactivity to psychological challenge as a potential risk factor for coronary artery disease and hypertension, and human and animal studies suggest that excessive reactivity may have some important psychosocial correlates. The overall objective of the proposed project is to further investigate the effects of social support on cardiovascular responsivity to challenge in humans, thereby advancing our understanding of one plausible mechanism by which social relationships might alter cardiovascular health. A model is employed which emphasizes two fundamental dimensions of interpersonal functioning -- dominance vs. submissiveness (here called "evaluation") and affiliation vs. hostility (here called "affilation"). The first two studies are designed to investigate how alterations in the affiliative and evaluative dimensions of interpersonal interaction with a partner can alter the partner's influence on a subject's cardiovascular responsiveness to a laboratory challenge. The second set of two studies is designed to investigate the mechanisms by which a partner's presence may alter cardiovascular reactivity, exploring the neutralizing impact of social affiliation on the performance incentive effects associated with social threat, and associated reductions in cardiovascular response. The third set of two studies is designed to examine the generalizability of the effects of social support on reactivity, exploring the influence of these effects in males and females, in individuals with coronary-prone behavior, and within the context of a primary relationship. Together, these three studies will advance our understanding of one of the mechanisms by which social processes may alter cardiovascular disease risk.

A growing body of evidence suggests that an individual's social network may be an important determinant of health and well-being -- for example, socially isolated individuals appear to be a greater risk for cardiovascular disease. Preliminary evidence implicates excessive cardiovascular reactivity to psychological challenge as a potential risk factor for coronary artery disease and hypertension; effects of social processes on cardiovascular reactivity would provide a potential mechanism by which social network characteristics may reduce health risk. Recent laboratory studies show that social affiliation reduces the effects of psychological challenge on cardiovascular reactivity. The generalizability of these laboratory effects are examined in this study by exploring the impact of socially supportive interactions on cardiovascular responsiveness to significant behavioral challenges in the course of everyday living. Subjects will be monitored intermittently over the course of a week-long period, providing cardiovascular assessments as well as information about environmental stressors, social stressors, and socially supportive transactions. Time series regression analyses will be used to examine the effects of these psychosocial factors on eliciting a moderating ambulatory cardiovascular responsivity. This study, a unique integration of three established methodologies (ambulatory cardiovascular monitoring, experience sampling using computer diary techniques, and ambulatory social interaction assessment) will advance our understanding of one of the mechanisms by which social processes may alter cardiovascular disease risk.

A growing body of evidence suggests that an individual's social network may be an important determinant of health and well-being -- for example, socially isolated individuals appear to be at greater risk for all causes of premature mortality, including mortality from cardiovascular disease. Preliminary evidence implicates excessive cardiovascular reactivity to psychological challenge as a potential risk factor for coronary artery disease and hypertension, and human and animal studies suggest that excessive reactivity may have some important psychosocial correlates. The overall objective of the proposed project is to further investigate the effects of social support on cardiovascular responsivity to challenge in humans, thereby advancing our understanding of one plausible mechanism by which social relationships might alter cardiovascular health. A model is employed which emphasizes two fundamental dimensions of interpersonal functioning -- dominance vs. submissiveness (here called "evaluation") and affiliation vs. hostility (here called "affilation"). The first two studies are designed to investigate how alterations in the affiliative and evaluative dimensions of interpersonal interaction with a partner can alter the partner's influence on a subject's cardiovascular responsiveness to a laboratory challenge. The second set of two studies is designed to investigate the mechanisms by which a partner's presence may alter cardiovascular reactivity, exploring the neutralizing impact of social affiliation on the performance incentive effects associated with social threat, and associated reductions in cardiovascular response. The third set of two studies is designed to examine the generalizability of the effects of social support on reactivity, exploring the influence of these effects in males and females, in individuals with coronary-prone behavior, and within the context of a primary relationship. Together, these three studies will advance our understanding of one of the mechanisms by which social processes may alter cardiovascular disease risk.

[unreadable] DESCRIPTION (provided by applicant): Accumulating evidence links psychosocial factors with the development of atherosclerosis. Much of this previous research has been conducted in nonhuman samples. Recent developments in the noninvasive assessment of subclinical atherosclerotic disease, along with the measurement of mental stress and stress responding, have allowed us to extend this type of investigation to human community samples, with important implications for risk stratification and prevention. During our initial funding period, we recruited a sample of 367 healthy men and women with no history of cardiovascular disease (50-70 years of age). Measures of psychosocial demands and social support were assessed during daily life, using a real-time electronic diary system. We also assessed individual differences in stress-related cardiovascular reactivity (CVR) using an automated test battery developed in our laboratory. These psychosocial factors were shown to be associated, as hypothesized, with ambulatory blood pressure (ABP), carotid artery atherosclerosis, by ultrasound, and, in some cases, with three-year carotid artery atherosclerotic progression as well. A number of gender differences in the association between psychosocial factors and atherosclerosis were observed. In this competing renewal application, we propose continuing to follow this sample for an additional 2-1/2 year funding period, with the following aims: a) to replicate and extend our initial findings on carotid atherosclerosis over a longer time course (total of 6 years), examining how psychosocial factors may be linked with the longer term trajectory of subclinical atherosclerosis in a healthy community sample; b) to determine whether changes in psychosocial factors over a 6-year time frame may be associated with commensurate alterations in the course of the disease, a question which may have implications for early intervention; c) to examine the extent to which psychosocial factors may be related to ABP changes over the 6-year follow-up period and to explore the extent to which such changes may contribute to atherosclerotic risk; and d) to determine the role of biological factors (specifically, the effects of autonomic function) and behavioral factors (specifically, the role of individual differences in verbal aggression) as possible determinants accounting for gender differences in the relationship between psychosocial factors and subclinical carotid artery disease progression. [unreadable] [unreadable]

"Hostility" refers to a set of characteristics that appear to be associated with diminished or dysregulated central serotonergic function, and that are linked, as well, with a number of lifestyle and biological variables associated with coronary heart disease (CHD) risk. For example, hostility has been shown to be associated with increased smoking and alcohol consumption, unhealthy dietary patterns, altered lipid concentrations, alterations in autonomic balance, increase stress-related cardiovascular responsiveness, and increased platelet activation. Accumulating evidence suggests that hostile characteristics are associated with increased risk for CHD events and mortality: These unhealthy behavioral and biological processes may account, in part, for the observed associations between hostility and CHD. Selective serotonin reuptake inhibitors (SSRIs), which increase the efficiency of serotonergic neurotransmission, have been shown to reduce hostile traits in psychiatric samples, and some evidence suggests that they may have similar effects in normal volunteers. There are no published data examining the effects of SSRI interventions on measures on hostility previously linked with CHD risk. Moreover, the potential impact of such interventions on multiple behavioral and biological variables of relevance to CHD has not been systematically explored. This project is a placebo-controlled trial designed to examine the effects of short term (3 month) SSRI treatment on changes in hostility and aggression in normal volunteers, selected for high hostility. We will also examine the effects of this intervention on changes in lifestyle- related behaviors associated with CHD risk, including smoking, alcohol consumption, and unhealthy dietary patterns; and on changes in biological markers of disease risk, including lipids, glucose and insulin, autonomic balance, stress-related cardiovascular responsiveness, and platelet activation. This research is important in 3 ways. First, it will help us to understand some of the CNS correlates of psychological traits relevant to CHD. Second, it will help us to explore some of the common origins of behavior and biological indices of CHD risk.. Second, it will help us explore some of the common origins of the behavioral and biological indices of CHD risk. And third, this research may eventually have implications for the development of new approaches to CHD risk factor intervention.

ABSTRACT NOT PROVIDED

Accumulating evidence supports the importance of chronic stress in the development of cardiovascular disease (CVD). One of the most consistent set of findings in this literature is the research on occupational stress. A growing literature is consistent with the "job strain" model, showing that chronic exposure to highly demanding and uncontrollable work environments may be linked with the development of clinical CVD as well as subclinical atherosclerosis. Much remains to be understood, however, about the potential mechanisms linking occupational stress and CVD, and the degree to which such mechanisms are specific to the workplace. For example, one assumption of the job strain model is that moment-to-moment behavioral processes account for the effects of occupational stress on health. This assumption is difficult to test using standard methodologies. We have recently developed state-of-the art computer-assisted ambulatory assessment procedures that allow us to capture the psychological and biological markers of mental stress over the course of daily life. Use of these procedures will allow us to examine, more precisely than has previously been possible, the mechanisms accounting for the health effects of occupational stress. 530 healthy employees (ages 30-55) will be administered ambulatory blood pressure (ABP) and electronic diary assessments over three working days and one nonworking (weekend) day. Global assessments of occupational stress will also be employed, along with risk factors and biomarkers for CVD, including ultrasound measures of carotid artery atherosclerosis. We will examine the role of "daily psychosocial strain," as assessed in real time in the natural environment, in explaining the association between occupational stress and CVD biomarkers. Both biological factors (hemodynamic and neuroendocrine factors) and health risk behaviors will be examined as potential mechanisms accounting for these effects, models that have been hypothesized but never explicitly tested. The role of daily demands outside of the workplace in contributing to the effects of occupational stress will be characterized, and the patterns of daily living accounting for sex differences in the relationship between occupational stress and biomarkers for CVD will also be examined. RELEVANCE: Identifying the behavioral and biological mechanisms by which occupational stress may contribute to cardiovascular disease is of critical importance for developing appropriate treatment targets and methods of intervention designed to reduce its effects.

[unreadable] DESCRIPTION (provided by applicant): Accumulating evidence is consistent with the possibility that psychosocial stress may moderate the effects of genetic factors on health and behavioral outcomes. Further advances in this area are predicated on the development of standardized, psychometrically sound instruments for quantifying exposures to psychosocial stress. Over the past several years, our research team has pioneered several state-of-the-art strategies for the assessment of psychosocial stress, including a new structured retrospective interview approach designed to quantify historical exposure to chronic stressors in human populations, and a real-time ecological momentary assessment (EMA) method designed to capture current psychological and physiological markers of mental stress as they emerge over the course of daily living. Building upon our ongoing experience and expertise, the goal of the current project is to translate each of these two assessment approaches into standardized field-deployable technologies that can be employed across multiple sites and populations. The current project is organized around a series of incremental studies that are designed to help us meet the following milestones: a) to develop efficient electronic data collection devices for administering, recording, and scoring self-report assessments relevant to each of these two novel assessment approaches, b) to refine the item content associated with each of these two data collection devices in a manner that will enhance validity, reliability, and item discrimination of the associated measures, c) to examine the reliability of the resulting instruments in a population representative sample and to determine optimal conditions of testing, and d) to document training and testing procedures associated with these methods, and to examine the feasibility of a pursuing the development of relevant production quality > devices for use in large scale research projects. The current proposal is a response to the RFA on "Field- deployable Tools for Quantifying Exposures to Psychosocial Stress and to Addictive Substances for Studies : of Health and Disease (U01) (RFA-DA-07-005)." Category 1 submission. RELEVANCE: In the presence of gene-environment interactions, reliable measures of environmental exposure, including exposure to psychosocial stress, are critical for quantifying the effects of genetic differences on health outcomes. [unreadable] [unreadable] [unreadable]

DESCRIPTION (provided by applicant): Novel Measures of Psychosocial Stress: Validation in an Ongoing Cohort Study There is increasing evidence that psychosocial stress may enhance the risk for a number of important chronic conditions, and that stress may moderate the effects of genetic factors on health and behavioral outcomes as well. In order to make further advances in this area, we must develop better standardized, psychometrically sound instruments for quantifying exposures to psychosocial stress. Over the past four years, our Pittsburgh- based team has been working to develop new tools for the assessment of psychosocial stress, under the auspices of a cooperative agreement sponsored by the Exposure Biology program (U01DA023821, Psychosocial stress exposure: Real-time and structured interview technologies). We have made a great deal of progress, and we now have in hand two new prototype technologies, one for the self-report assessment of daily psychosocial stress (SMART, or self-report mobile activity recording tool), and the other, an interviewer- assisted assessment tool for the measurement of chronic and acute environmental stressors (LEAP, or Life Events Assessment Profile). The goal of the proposed study will be to validate these two prototype devices in the context of an ongoing epidemiological study at an offsite location. This research will permit us to establish the validity of the SMART and the LEAP as measures of psychosocial stress and health risk, and will provide us with important background and experience field testing these devices, so that we may ultimately use these measures as part of multi-site epidemiological studies.

DESCRIPTION (provided by applicant): Social integration, that is, participation in multiple social roles, is associated with reduced morbidity and mortality risk. Midlife appears to be a critical period for observing these effects, as social networks are most robust during this stage of life, and health declines after middle age. Evidence suggests that social integration may be important in regulating emotion, in promoting health behavior, and in modulating biological processes that may be related to disease. Little is understood, however, about how daily social interactions may contribute to these effects. In this study, we will follow a group of 400 community adults over a one-week period, sampling daily social interactions concurrently with affective, behavioral, and biological markers of health risk. We will examine whether socially integrated people show more adaptive patterns of emotion, health behavior (diet, physical activity, smoking, and alcohol use), and physiology (ambulatory blood pressure, cortisol, metabolic and inflammatory responses). We will also examine how features of daily social interaction, including the diversity of social role interactions during daily life, and the frequeny of contact with others who exhibit negative health behaviors, may contribute to these effects. We will examine the extent to which socially integrated people are relatively protected from the effects of stress and social pressures when it comes to these measures, and we will examine the extent to which some of the effects we observe may be accounted for, in part, by associated features of the person (cognitive style or personality traits) or the nature of their daily activites.

ABSTRACT Project 2 (Thomas Kamarck, PL) A neurobiological diathesis-stress model of CVD risk Psychosocial stress has been associated with risk for cardiovascular disease (CVD), and emerging evidence suggests that individuals may differ in their susceptibility to this stress-related risk. Project 2 will examine whether the activity of brain areas that coordinate autonomic and endocrine output to internal organs (called `visceral control areas') may help to explain some of these individual differences in stress susceptibility during daily life, and may also moderate the effects of psychosocial stress on preclinical CVD progression. Importantly, growing evidence indicates that physical activity (PA) modifies the influence of visceral control areas on peripheral physiology, and this influence may represent a source of resilience to reduce stress susceptibility. Accordingly, Project 2 also aims to test how individual differences in the functioning of visceral control areas may partly explain the association between PA and daily stress susceptibility effects. Specifically, we will follow 350 midlife and community dwelling adults over a 32-month period, collecting two one-week samples, at the beginning and at the end of this period. At each of these 2 points, we will assess daily psychosocial stressors using multiple momentary electronic diary reports and ambulatory blood pressure readings. We will use daily actigraphy to assess habitual PA, and we will collect biological markers of subclinical CVD. At baseline, all participants will complete a standardized battery of stressor tasks during fMRI. We will test whether individual differences in the functionality of visceral control areas (that is, differences stressor-evoked functional connectivity) predict corresponding differences in susceptibility to psychosocial stress in the natural environment. We hypothesize that people who exhibit greater stressor- evoked functional connectivity among visceral control areas will also exhibit a) larger blood pressure reactions to daily psychosocial stressors in the natural environment, and b) stronger associations between psychosocial stressor exposures and 32-month preclinical CVD progression. We further hypothesize that stressor-evoked functional connectivity will partly account for the effects of PA on daily stress-related blood pressure reactivity. The public health significance of this novel work is that understanding the role of particular brain circuits in stress susceptibility and CVD risk will help us to better measure and, potentially, to enhance stress resilience through more targeted intervention efforts.