Denise Janicki-Deverts

Chronic stress, glucocorticoid receptor resistance, inflammation, and disease risk

We propose a model wherein chronic stress results in glucocorticoid receptor resistance (GCR) that, in turn, results in failure to down-regulate inflammatory response. Here we test the model in two viral-challenge studies. In study 1, we assessed stressful life events, GCR, and control variables including baseline antibody to the challenge virus, age, body mass index (BMI), season, race, sex, education, and virus type in 276 healthy adult volunteers. The volunteers were subsequently quarantined, exposed to one of two rhinoviruses, and followed for 5 d with nasal washes for viral isolation and assessment of signs/symptoms of a common cold. In study 2, we assessed the same control variables and GCR in 79 subjects who were subsequently exposed to a rhinovirus and monitored at baseline and for 5 d after viral challenge for the production of local (in nasal secretions) proinflammatory cytokines (IL-1β, TNF-α, and IL-6). Study 1: After covarying the control variables, those with recent exposure to a long-term threatening stressful experience demonstrated GCR; and those with GCR were at higher risk of subsequently developing a cold. Study 2: With the same controls used in study 1, greater GCR predicted the production of more local proinflammatory cytokines among infected subjects. These data provide support for a model suggesting that prolonged stressors result in GCR, which, in turn, interferes with appropriate regulation of inflammation. Because inflammation plays an important role in the onset and progression of a wide range of diseases, this model may have broad implications for understanding the role of stress in health.

Childhood socioeconomic status and adult health

Socioeconomic status (SES) exposures during childhood are powerful predictors of adult cardiovascular morbidity, cardiovascular mortality, all‐cause mortality, and mortality due to a range of specific causes. However, we still know little about when childhood SES exposures matter most, how long they need to last, what behavioral, psychological, or physiological pathways link the childhood SES experience to adult health, and which specific adult health outcomes are vulnerable to childhood SES exposures. Here, we discuss the evidence supporting the link between childhood and adolescent SES and adult health, and explore different environmental, behavioral, and physiological pathways that might explain how early SES would influence adult health. We also address the ages when SES exposures matter most for setting adult health trajectories as well as the role of exposure duration in SES influences on later health. While early childhood exposures seem to be potent predictors of a range of health outcomes, we emphasize that later childhood and adolescent exposures are risks for other health outcomes.

Sleep Habits and Susceptibility to the Common Cold

BACKGROUND Sleep quality is thought to be an important predictor of immunity and, in turn, susceptibility to the common cold. This article examines whether sleep duration and efficiency in the weeks preceding viral exposure are associated with cold susceptibility. METHODS A total of 153 healthy men and women (age range, 21-55 years) volunteered to participate in the study. For 14 consecutive days, they reported their sleep duration and sleep efficiency (percentage of time in bed actually asleep) for the previous night and whether they felt rested. Average scores for each sleep variable were calculated over the 14-day baseline. Subsequently, participants were quarantined, administered nasal drops containing a rhinovirus, and monitored for the development of a clinical cold (infection in the presence of objective signs of illness) on the day before and for 5 days after exposure. RESULTS There was a graded association with average sleep duration: participants with less than 7 hours of sleep were 2.94 times (95% confidence interval [CI], 1.18-7.30) more likely to develop a cold than those with 8 hours or more of sleep. The association with sleep efficiency was also graded: participants with less than 92% efficiency were 5.50 times (95% CI, 2.08-14.48) more likely to develop a cold than those with 98% or more efficiency. These relationships could not be explained by differences in prechallenge virus-specific antibody titers, demographics, season of the year, body mass, socioeconomic status, psychological variables, or health practices. The percentage of days feeling rested was not associated with colds. CONCLUSION Poorer sleep efficiency and shorter sleep duration in the weeks preceding exposure to a rhinovirus were associated with lower resistance to illness.

Can We Improve Our Physical Health by Altering Our Social Networks

Persons with more types of social relationships live longer and have less cognitive decline with aging, greater resistance to infectious disease, and better prognoses when facing chronic life-threatening illnesses. We have known about the importance of social integration (engaging in diverse types of relationships) for health and longevity for 30 years. Yet, we still do not know why having a more diverse social network would have a positive influence on our health, and we have yet to design effective interventions that influence key components of the network and in turn physical health. Better understanding of the role of social integration in health will require research on how integrated social networks influence health relevant behaviors, regulate emotions and biological responses, and contribute to our expectations and worldviews.

Childhood abuse, parental warmth, and adult multisystem biological risk in the Coronary Artery Risk Development in Young Adults study

Significance Adverse social relations in early life are thought to negatively influence health throughout the lifespan. The present findings provide a biological link regarding why negative early life experiences affect health and further suggest that a loving parental figure may provide protection. It is well recognized that providing children in adverse circumstances with a nurturing relationship is beneficial for their overall wellbeing. Our findings suggest that a loving relationship may also prevent the rise in biomarkers indicative of disease risk across numerous physiological systems, impacting adverse health outcomes decades later. The results contribute in a meaningful way to several biological literatures and to the social sciences and, as such, will have a substantial impact. Childhood abuse increases adult risk for morbidity and mortality. Less clear is how this “toxic” stress becomes embedded to influence health decades later, and whether protective factors guard against these effects. Early biological embedding is hypothesized to occur through programming of the neural circuitry that influences physiological response patterns to subsequent stress, causing wear and tear across multiple regulatory systems. To examine this hypothesis, we related reports of childhood abuse to a comprehensive 18-biomarker measure of multisystem risk and also examined whether presence of a loving parental figure buffers against the impact of childhood abuse on adult risk. A total of 756 subjects (45.8% white, 42.7% male) participated in this ancillary substudy of the Coronary Artery Risk Development in Young Adults Study. Childhood stress was determined by using the Risky Families Questionnaire, a well-validated retrospective self-report scale. Linear regression models adjusting for age, sex, race, parental education, and oral contraceptive use found a significant positive relationship between reports of childhood abuse and multisystem health risks [B (SE) = 0.68 (0.16); P < 0.001]. Inversely, higher amounts of reported parental warmth and affection during childhood was associated with lower multisystem health risks [B (SE) = −0.40 (0.14); P < 0.005]. A significant interaction of abuse and warmth (P < 0.05) was found, such that individuals reporting low levels of love and affection and high levels of abuse in childhood had the highest multisystem risk in adulthood.

Behaviorally Assessed Sleep and Susceptibility to the Common Cold

STUDY OBJECTIVES Short sleep duration and poor sleep continuity have been implicated in the susceptibility to infectious illness. However, prior research has relied on subjective measures of sleep, which are subject to recall bias. The aim of this study was to determine whether sleep, measured behaviorally using wrist actigraphy, predicted cold incidence following experimental viral exposure. DESIGN, MEASUREMENTS, AND RESULTS A total of 164 healthy men and women (age range, 18 to 55 y) volunteered for this study. Wrist actigraphy and sleep diaries assessed sleep duration and sleep continuity over 7 consecutive days. Participants were then quarantined and administered nasal drops containing the rhinovirus, and monitored over 5 days for the development of a clinical cold (defined by infection in the presence of objective signs of illness). Logistic regression analysis revealed that actigraphy- assessed shorter sleep duration was associated with an increased likelihood of development of a clinical cold. Specifically, those sleeping < 5 h (odds ratio [OR] = 4.50, 95% confidence interval [CI], 1.08-18.69) or sleeping between 5 to 6 h (OR = 4.24, 95% CI, 1.08-16.71) were at greater risk of developing the cold compared to those sleeping > 7 h per night; those sleeping 6.01 to 7 h were at no greater risk (OR = 1.66; 95% CI 0.40-6.95). This association was independent of prechallenge antibody levels, demographics, season of the year, body mass index, psychological variables, and health practices. Sleep fragmentation was unrelated to cold susceptibility. Other sleep variables obtained using diary and actigraphy were not strong predictors of cold susceptibility. CONCLUSIONS Shorter sleep duration, measured behaviorally using actigraphy prior to viral exposure, was associated with increased susceptibility to the common cold.

Association Between Telomere Length and Experimentally Induced Upper Respiratory Viral Infection in Healthy Adults

IMPORTANCE Although leukocyte telomere length is associated with mortality and many chronic diseases thought to be manifestations of age-related functional decline, it is not known whether it relates to acute disease in younger healthy populations. OBJECTIVE To determine whether shorter telomeres in leukocytes, especially CD8CD28- T cells, are associated with decreased resistance to upper respiratory infection and clinical illness in young to midlife adults. DESIGN, SETTING, AND PARTICIPANTS Between 2008 and 2011, telomere length was assessed in peripheral blood mononuclear cells (PBMCs) and T-cell subsets (CD4, CD8CD28+, CD8CD28-) from 152 healthy 18- to 55-year-old residents of Pittsburgh, Pennsylvania. Participants were subsequently quarantined (single rooms), administered nasal drops containing a common cold virus (rhinovirus 39), and monitored for 5 days for development of infection and clinical illness. MAIN OUTCOME MEASURES Infection (virus shedding or 4-fold increase in virus-specific antibody titer) and clinical illness (verified infection plus objective signs of illness). RESULTS Rates of infections and clinical illness were 69% (n = 105) and 22% (n = 33), respectively. Shorter telomeres were associated with greater odds of infection, independent of prechallenge virus-specific antibody, demographics, contraceptive use, season, and body mass index (PBMC: odds ratio [OR] per 1-SD decrease in telomere length, 1.71 [95% CI, 1.08-2.72]; n = 128 [shortest tertile 77% infected; middle, 66%; longest, 57%]; CD4: OR, 1.76 [95% CI, 1.15-2.70]; n = 146 [shortest tertile 80% infected; middle, 71%; longest, 54%]; CD8CD28+: OR, 1.93 [95% CI, 1.21-3.09], n = 132 [shortest tertile 84% infected; middle, 64%; longest, 58%]; CD8CD28-: OR, 2.02 [95% CI, 1.29-3.16]; n = 144 [shortest tertile 77% infected; middle, 75%; longest, 50%]). CD8CD28- was the only cell population in which shorter telomeres were associated with greater risk of clinical illness (OR, 1.69 [95% CI, 1.01-2.84]; n = 144 [shortest tertile, 26%; middle, 22%; longest, 13%]). The association between CD8CD28- telomere length and infection increased with age (CD8CD28- telomere length × age interaction, b = 0.09 [95% CI, 0.02-0.16], P = .01, n = 144). CONCLUSION AND RELEVANCE In this preliminary study among a cohort of healthy 18- to 55-year-olds, shorter CD8CD28- T-cell telomere length was associated with increased risk for experimentally induced acute upper respiratory infection and clinical illness.

Does Hugging Provide Stress-Buffering Social Support? A Study of Susceptibility to Upper Respiratory Infection and Illness

Perceived social support has been hypothesized to protect against the pathogenic effects of stress. How such protection might be conferred, however, is not well understood. Using a sample of 404 healthy adults, we examined the roles of perceived social support and received hugs in buffering against interpersonal stress-induced susceptibility to infectious disease. Perceived support was assessed by questionnaire, and daily interpersonal conflict and receipt of hugs were assessed by telephone interviews on 14 consecutive evenings. Subsequently, participants were exposed to a virus that causes a common cold and were monitored in quarantine to assess infection and illness signs. Perceived support protected against the rise in infection risk associated with increasing frequency of conflict. A similar stress-buffering effect emerged for hugging, which explained 32% of the attenuating effect of support. Among infected participants, greater perceived support and more-frequent hugs each predicted less-severe illness signs. These data suggest that hugging may effectively convey social support.

Childhood socioeconomic status, telomere length, and susceptibility to upper respiratory infection ☆

Low socioeconomic status (SES) during childhood and adolescence has been found to predict greater susceptibility to common cold viruses in adults. Here, we test whether low childhood SES is associated with shorter leukocyte telomere length in adulthood, and whether telomere length mediates the association between childhood SES and susceptibility to acute upper respiratory disease in adulthood. At baseline, 196 healthy volunteers reported whether they currently owned their home and, for each year of their childhood, whether their parents owned the family home. Volunteers also had blood drawn for assessment of specific antibody to the challenge virus, and for CD8+ CD28- T-lymphocyte telomere length (in a subset, n=135). They were subsequently quarantined in a hotel, exposed to a virus (rhinovirus [RV] 39) that causes a common cold and followed for infection and illness (clinical cold) over five post-exposure days. Lower childhood SES as measured by fewer years of parental home ownership was associated with shorter adult CD8+ CD28- telomere length and with an increased probability of developing infection and clinical illness when exposed to a common cold virus in adulthood. These associations were independent of adult SES, age, sex, race, body mass, neuroticism, and childhood family characteristics. Associations with infections and colds were also independent of pre-challenge viral-specific antibody and season. Further analyses do not support mediating roles for smoking, alcohol consumption or physical activity but suggest that CD8+ CD28- cell telomere length may act as a partial mediator of the associations between childhood SES and infection and childhood SES and colds.

Depressive symptoms moderate the influence of hostility on serum interleukin-6 and C-reactive protein.

Objective: Recent evidence suggests that depressive symptoms and hostility may act together, as interacting factors, to have an effect on the circulating levels of inflammatory markers relevant to coronary artery disease. Further research, however, is needed to clarify the nature of this interaction and to determine whether previous findings extend to older adults. In this report we examined the cross-sectional associations of depressive symptoms, hostility, and their interaction with circulating levels of two such inflammatory markers—interleukin-6 (IL-6) and C-reactive protein (CRP). Methods: A total of 316 healthy, older adults underwent a blood draw for the assessment of serum IL-6 and CRP and completed the Beck Depression Inventory-II and the Cook-Medley Hostility Scale. Regression analyses were performed to examine depressive symptoms, hostility, and their interaction as predictors of serum IL-6 and CRP. Results: After adjustment for demographic factors, cardiovascular risk factors, and health behaviors, we detected depressive symptoms × hostility interactions for serum IL-6 (&Dgr;R2 = .027, p < .01) and CRP (&Dgr;R2 = .015, p < .05). Simple slope analyses revealed that hostility was positively related to serum IL-6 only among individuals with higher depressive symptoms. The pattern of results was similar for serum CRP, although none of the simple slopes was significant. Conclusions: Our findings suggest that depressive symptoms may moderate the hostility-inflammation relationship such that hostility may augment inflammatory processes relevant to coronary artery disease only in the presence of depressive symptoms. Our results also extend previous findings from younger adults to older adults from the general community. IL-6 = interleukin-6; CRP = C-reactive protein; CAD = coronary artery disease; BDI = Beck Depression Inventory; Ho Scale = Cook-Medley Hostility Scale; TNF-&agr; = tumor necrosis factor-&agr;; PHHP = Pittsburgh Healthy Heart Project; SBP = systolic blood pressure; DBP = diastolic blood pressure; MAP = mean arterial pressure; BMI = body mass index; HDL = high-density lipoprotein; LDL = low-density lipoprotein.