Linkages among the Social Environment, Stress &

Physiological Dysregulation

Noreen GoldmanThe University of Colorado Population Center &

Institute of Behavioral ScienceSummer Course in Biodemography

June 11-13, 2007

The Basic Model

PhysiologicalResponse

Life ChallengesSources of Stress

Physical & MentalHealth & Illness

Position in Social HierarchiesSocial Connection and Networks

Social Environment

Three Big Questions1. What are the physiological pathways

linking “stress” & health/survival?2. Do physiological markers of “stress”

account for SES differences in health & survival?

3. How well do these physiological markers (i.e., physiological dysregulation) predict health and survival?

Question 3: Physiological Dysregulation & Health

This is the “easiest” of the 3 questionsWe will focus on cumulative measures of AL (PD) on health in a general population (humans)

There are zillions of studies of individual markers and health, many clinical

There are many dimensions to health status: mental, physical, cognitive, illness, disability, survival.

We will look at some of these

We will focus on longitudinal studies because of potential reverse causality.

What are we worried about here?

AL and Health/Survival: MacArthurThere is considerable evidence from MacArthur that, as a group, these biomarkers matter

Seeman et al. (1997) High AL scores predicted larger declines in cognitive & physical functioning and increased incidence of CV disease in MacArthur studySeeman et al. (2001) Higher baseline AL scores associated with increased risk for 7-year mortality

MacArthur: Association between PD score and Health

Source: Seeman, TE et al. 2004. Cumulative biological risk and socio-economic differences in mortality: MacArthur Studies of Successful Aging. Soc Sci Med, 1985-1997

Odds ratios for 7.5 year mortality rate by AL score (2-7)

AL and Health/Survival: MacArthurKarlmangla et al. (2004) demonstrate the importance of primary mediators, not just syndrome X markers, for physical & cognitive declines

This is critical because we would expect some of these markers to be associated with CV disease, physical function and survivalNote that these results suggest that not all biomarkers should carry equal weight

MacArthur: Contribution of Various Biomarkers from Canonical Correlation

Source: Karlamangla et al. 2002. Allostatic load as a predictor of functional decline MacArthur studies of successful aging. Journal of Clinical Epidemiology, 696-710.

Canonical weights for each biomarker, for physical & cognitive decline

AL and Health/Survival: TaiwanSEBAS (Taiwan) yields similar conclusions

Goldman et al. (2006) show that PD score predicts changes in physical & cognitive functioning, depressive symptoms & survival over 3-year period

SEBAS confirms that primary mediators as well as secondary outcomes predict health

Neuroendocrine & immune markers appear to be at least as important as CV markers for survival in Taiwan

Association between PD score and Health: Taiwan

Source: Goldman N et al. 2006. Physiological dysregulation and changes in health in an older population. Experimental Gerontology, 862-870.

Predicted health outcomes by PD score (0,3,6,9)

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Baseline model

Standard Clinical

Nontraditional

AUC test indicates that non-clinical measures, but not clinical, predict better than baseline model.Sensitivity = probability regression model correctly predicts deaths for those who died; 1-Specificity = probability of an incorrect prediction for those who survived

ROC Curves Predicting Mortality 2000-2003 in Taiwan

Baseline model: sociodemographic& health variables

Prediction based on individual markers rather than PD score

Non-Clinical Model

Question 1: How strong is the link between “stress” and these biomarkers?

This is not quite the same question 1What are the physiological pathways linking stress and health/survival?

First, we need to determine what we mean by “stress”1. Key life events or challenges in an individual’s

environment, chronic stressors2. Individuals’ perceptions or evaluations of

these events, appraisal of events, perceived stress

3. Biological response to stressors – activation of HPA, SNS, immune systems, physiological dysregulation

A Simple Model of the Stress Response

ChronicStressors

IndividualCharacteristics

PhysiologicalDysregulation

PerceivedStress

SocialEnvironment

Physical &Mental Health

(2)(1) (3)

What do we Know from the Literature about Stress and Physiological Dysregulation?

Few studies look at perceptions of stressMuch of the literature focuses on acute stressors

For example, public speaking, backward subtractions

Relatively sparse literature on chronic stressorsChronic stressors include stressful life events, stressful situation (e.g., caregiver), and especially PTSDMuch of the literature focuses on individual biomarkers, particularly cortisol (research suggests that chronic stressors are associated with both low and high cortisol)The few studies of other biomarkers (E, NE, blood pressure, lipids, DHEAS, IL-6, HbA1c, obesity)) have mixed findings (e.g., some studies find significant associations, others do not)Most studies of chronic stressors focus on elevations in levels of the physiological parameters rather than blunted levels

Four Studies of Chronic Stressors and (Multi-system) Physiological Dysregulation

Singer & Ryff (1999)Examines small subsample of persons in Wisconsin Longitudinal StudyDifficult economic circumstances and poor social relations (with parent as a child and with spouse) are associated with higher AL (10-item)*

Schnorpfeil et al. (2003)Examines workers in a manufacturing plant for airline parts in urban area of Germany; extensive information on their job characteristics and demands; cross-sectionalOnly one of numerous aspects of job is associated with AL (14-item): job demands Concludes that association between AL and self-reported adverse work characteristics is weak

* Note that several studies (esp. from MacArthur) have looked at social deprivation and AL, with implicit assumption that poor social ties denotes chronic stress

Studies of Chronic Stressors, con’tClark et al. (2007)

Examines caregiving for small sample of dementia patients in Australia AL score (10-item) for primary mediators (not secondary outcomes) goes up in 2-year period only for caregivers

Glei et al. (2007)Based on Taiwan sample (1996-2003)Examines large number of stressful events and subsequent PD (16-item)Significant but modest association between # of chronic stressors and PD only for those with high psychosocial vulnerability (low on SES, social ties, locus of control, optimism) Underscores the notion that social and personality factors are moderating variables

So, the jury is still out

What about Perceived Stress & PD?

SEBAS questions used to create an index of perceived stress: Do the following situations make you anxious (own or family finances, job, social relationships, health)?SEBAS analysis (Goldman et al., 2005) found:

Some biomarkers (5 out of 16) have significant (p<.05) associations with an index of perceived stress (cortisol, IL-6, DHEAS, trigylcerides, fasting glucose).Many biomarkers reveal no association (blood pressure, markers of obesity, total cholesterol).

PD score is significantly but modestly associated with perceived stress:

Perceived stress in all 3 waves is associated with about 2/3 of a point higher on PD score

SEBAS: Perceived Stress & PD

Source: Goldman N et al. 2005. Perceived stress and physiological dysregulation regulation in older adults. Stress, 95-105.

Regression of PD score on perceived stress score

Sidenote on Stress & HealthThere are numerous studies that look at chronic stressors or perceived stress and health outcomes (not physiological dysregulation)A clever & unusual “experiment” is Cohen et al. (1991, 2001)

Studies in England and Pittsburg to link stress & common coldFor a healthy sample at baseline, examine association between (1) major stressful events in past year & perceptions of stress & (2) immune response to nasal solution of respiratory virus (or placebo). Subjects were quarantined for 1 week to identify symptoms of cold.Results show that higher levels of stressful events are associated with greater likelihood of developing a cold.

Cohen Studies on Stress & Common Cold

Source: Cohen S et al., 1991. Psychological stress and susceptibility to the common cold. NEJM, 606-612

Source: Cohen S. 2001.Social relationships and susceptibility to the common cold. Pp.221-242 in Carol D. Ryff and Burton H. Singer (eds.) Emotion, Social Relationships, and Health. New York: Oxford University Press, Inc.

Odds Ratios for Developing a Cold by Nature of Difficulties

Percent Developing a Cold by Stress Index

How Should We Measure Chronic Stressors and Perceptions of Stress?

Traumatic events? Major life events? Repeated daily hassles?What about intensity, duration and timing?What about perceptions of stress?

Most frequently used measure is Cohen Perceived Stress Scale (10 or 14-item validated instrument looking at appraisal of stress, containing some questions similar to depression or locus of control instruments)

Cohen Perceived Stress Scale (10-item)

Source: Cohen S et al. 1983. A Global Measure of Perceived Stress. Journal of Health and Social Behavior, 385-396.

Question 2: A Follow-up QuestionDoes the link between chronic stressors and physiological dysregulation help us to understand the (almost) ubiquitous associations between socioeconomic status and health

i.e., is the social gradient in health due to higher levels of stress (and hence higher PD) for lower SES?

This is a major question in the social epidemiology literatureLet’s start by taking a step back and thinking about the pathways relating SES to health outcomes

Pathways Linking SES to Health Outcomeso Access to medical care (treatment & prevention)o Access to information regarding health & medical careo Patterns of health risk behaviors (smoking, obesity)o Exposure to risky environments & infections (stressful

situations)o Access to resources that mediate consequences of

stresso Ability to control one’s environment, self-mastery,

power, hostility (psychosocial influences)o Availability of social ties & supporto Early life conditions

e.g., infection, nutrition, fetal conditions, birthweighte.g., “risky” family social environments

SES → Stress →HealthThus, “stress” enters the scene in at least 2 important ways!

Low SES → more (frequent) stressful eventsLow SES → greater psychosocial vulnerability (greater physiological response) to stressorsNote that research has NOT done a good job of making this differentiation.

Nature of the Argument“Psychosocial” factors,” affect physiology by stimulating

the central nervous system (via SNS, HPA, immune systems), becoming a major source of health inequalities, more important than “material” factors.

Some arguments emanate from demonstrations that SES is related to biological factors or, in some cases, that psychosocial factors (hostility, low job control) are related to biological factors (e.g., Whitehall Studies in London).

But, as we will see, there is far from compelling evidence that the SES gradient in health is driven by “stress.”

Nature of the Argument, con’tThis link, SES → Physiological Markers of Stress → Health, can be important only if there is evidence that low SES is associated with “at risk” values of stress-related biomarkers (& with mortality).

Most studies have focused on CV factorsLittle analysis of neuroendocrine & immune markersSome reports/studies (especially Whitehall) suggest more consistent patterns than a more thorough review of the literature indicates

A Few Studies Have Looked at SES → Physiological Dysregulation → Health

Mac Arthur (Seeman et al., 2004)How much do AL biological risk factors (individually and by system) mediate the effect of education on 7.5 year mortality?Conclusion is that the summary measure of AL accounts for ≈ one-third of education effects

But, some markers (peak flow, which is not a conventional marker of stress) – have much larger effects than others (cortisol in particular)*!

* SEBAS also finds no link between SES & cortisol

MacArthur: Education, Biomarkers & Mortality

Source: Seeman, TE et al. 2004. Cumulative biological risk and socio-economic differencesin mortality: MacArthur Studies of Successful Aging. Soc Sci Med, 1985-1997

Effect of each biomarker on the education coefficient for logistic regression of 7.5 year mortality rate

SEBAS: Education, Biomarkers & Health/Mortality

SEBAS: Biomarkers have little effect on the coefficients linking education to

3-year mortality (Turra et al., 2005);Cross-sectional measures of mobility difficulties and SRH (5-category response to health status; Dowd & Goldman, 2006)These weak associations arise because SES shows little consistent association with biomarkers

CRELES (Costa Rica):High and low SES are equally likely to be associated with “at risk” values of biomarkers

So, research to date does not identify a clear mediating role for biomarkers of stress in SES-health relationship

SEBAS: Education & Mortality – Effects of Adding Biomarkers

Model 1: Social or demographic variables

Model 2: Self reports of physical and mental health added to (1)

Model 3: Biomarkers (linear and quadratic) added to (2)

Source: Turra CM et al., 2005. Determinants of Mortality at Older Ages: The Role of Biological Markers of Chronic Disease. Pop Dev Review, 675-698.

Logistic models of 3-year probability of dying

SEBAS: Education & Health (SRH, Mobility) – Effects of Adding Biomarkers

Source: Dowd JB and N Goldman.2006. Do biomarkers of stress mediate the relation between socioeconomic status and health? J Epidemiol Community Health, 633-639.

Odds ratios of reporting worse health by education and income

Much Work Remains to be DoneA review of the major problems inherent in using large-scale surveys to examine these linkages

Obtaining the “correct” biomarkers (and measures!) at enough time pointsObtaining useful & reliable measures of chronic stressorsObtaining information on potential mediators of stressors (“vulnerability”)Knowing how to include large amounts of information (and interactions) in statistical modelsUnderstanding variation (e.g., across countries and age groups).

Would we expect links in Taiwan to be weaker than those found in the U.S.?