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Abstract from: Journal of the American Medical Association (2013), 309, 699-705.

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

Cohen, S., Janicki-Deverts, D., Turner, R. B., Casselbrant, M. L., Li-Korotky, H., Epel, E. S., & Doyle, W. J.

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 x 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.

Abstract from: American Journal of Respiratory and Critical Care Medicine (2012), 186, 147-154.

Prenatal and Postnatal Maternal Stress and Wheeze in Urban Children: Effect of Maternal Sensitization

Yueh-Hsiu, M.C., Coull, B .A., Cohen, S., Wooley, A., & Wright, R. J.

Rationale: Critical periods for programming early wheeze risk may include pregnancy and infancy. Effects of timing remain poorly understood. Objectives: Associations among prenatal and postnatal maternal stress and children's wheeze were prospectively examined in 653 families. Effect modification by maternal sensitization was also examined. Methods: Stress was indexed by a maternal negative life events (NLEs) score (range, 0–9) ascertained during pregnancy and between 1 and 2 years postpartum. Mothers reported child wheeze every 3 months up to age 2 years. Relationships of prenatal and postnatal maternal NLEs with repeated wheeze (≥2 episodes) were examined using logistic regression adjusting for covariates. Penalized splines were implemented to explore possible nonlinear associations. We also examined the interaction between prenatal stress and maternal sensitization indexed by allergen-specific IgE from maternal prenatal serum. Measurements and Main Results: Adjusted models considering prenatal or postnatal NLEs alone both showed an exposure-response relationship between higher stress and child wheeze.When considering prenatal and postnatal stress concurrently, only children of mothers with high stress in both periods were significantly more likely to wheeze (adjusted odds ratio, 3.04; 95% confidence interval, 1.67–5.53) than children of mothers reporting low stress in both periods. Associations between high prenatal stress and wheeze were significant in children born to nonsensitized mothers (any IgE ‹ 0.35 kU/L) but not in the sensitized group (P for interaction = 0.03). Conclusions: Although children have heightened sensitivity to maternal stress in utero and in early childhood, those with higher stress in both periods were particularly at risk for wheeze. The prenatal maternal immune milieu modified effects.

Abstract from: Sleep (2012), 35, 1063-1069.

Sleep and Antibody Response to Hepatitis B Vaccination

Prather, A. A., Hall, M., Fury, J. M., Ross, D. C., Mulddon, M. F., Cohen, S., & Marsland, A.

Study Objectives: Experimental evidence links poor sleep with susceptibility to infectious illness; however, it remains to be determined if naturally occurring sleep is associated with immune responses known to play a role in protection against infection. The aim of this study was to determine whether sleep duration, sleep efficiency, and sleep quality, assessed in the natural environment, predict magnitude of antibody responses to a novel antigen among community volunteers in midlife. Design: Observational. Measurements and Results: Healthy midlife adults (n = 125; 70 female; age 40-60 yr) received the standard 3-dose hepatitis B vaccination series. Actigraphy and electronic sleep diaries were used to assess sleep duration, sleep efficiency, and subjective sleep quality. Viral-specific antibody titers were obtained prior to the 2nd and 3rd vaccination to assess primary and secondary antibody responses. Clinical protection status (anti-hepatitis B surface antigen immunoglobulin G ≥ 10 mIU/ml) was assessed 6 m after the final immunization. Regression analyses revealed that shorter actigraphy-based sleep duration was associated with a lower secondary antibody response independent of age, sex, body mass index, and response to the initial immunization. Shorter sleep duration, measured by actigraphy and sleep diary, also predicted a decreased likelihood of being clinically protected from hepatitis B at the conclusion of the vaccination series. Neither sleep efficiency nor subjective sleep quality were significant predictors of antibody response. Conclusions: Short sleep duration in the natural environment may negatively affect in vivo antibody responses to novel antigens, providing a possible explanation for observed associations of poor sleep with increased susceptibility to infectious disease.

Abstract from: Psychosomatic Medicine (2012), 74, 728-735.

Sex Differences in the Association of Childhood Socioeconomic Status with Adult Blood Pressure Change: The CARDIA Study

Janicki-Deverts, D., Cohen, S., Matthews, K. A., & Jacobs, D. R., Jr.

Objective: To examine sex differences in the relation of childhood socioeconomic status (CSES) to systolic (SBP) and diastolic blood pressure (DBP) trajectories during 15 years, spanning young (mean [M] [standard deviation {SD}] = 30 [3] years) and middle (M [SD] = 45 [3] years) adulthood, independent of adult SES. Methods: A total of 4077 adult participants reported father's and mother's educational attainments at study enrollment (Year 0) and own educational attainment at enrollment and at all follow-up examinations.Resting BP also was measured at all examinations. Data from examination Years 5 (when participantM[SD] age = 30 [3] years), 7, 10, 15, and 20 are examined here. Associations of own adult (Year 5), mother's, and father's educations with 15-year BP trajectories were examined in separate multilevel models. Fully controlled models included time-invariant covariates (age, sex, race, recruitment center) and time-varying covariates that were measured at each examination (marital status, body mass, cholesterol, oral contraceptives/ hormones, and antihypertensive drugs). Analyses of parental education controlled for own education. Results: When examined without covariates, higher education -- own (SBP y = -0.03, DBP y = -0.03), mother's (SBP y = -0.02, DBP y = -0.02), and father's (SBP y = -0.02, DBP y = -0.01) -- were associated with attenuated 15-year increases in BP (p ‹ .001). Associations of own (but not either parent's) education with BP trajectories remained independent of standard controls. Sex moderated the apparent null effects of parental education, such that higher parental education -- especially mother's, predicted attenuated BP trajectories independent of standard covariates among women (SBP y = -0.02, p = .02; DBP y = -0.01, p = .04) but not men (SBP y = 0.02, p = .06; DBP y = 0.005, p = .47; p interaction SBP ‹ .001, p interaction DBP = .01). Conclusions: Childhood socioeconomic status may influence women's health independent of their own adult status.

Abstract from: Brain, Behavior and Immunity (2012), 26, 1128-1135.

The Prospective Association of Socioeconomic Status with C-Reactive Protein Levels in the CARDIA Study

Janicki-Deverts, D., Cohen, S., Kalra, P., & Matthews, K. A.

Better health is a well-documented benefit of having a higher socioeconomic status (SES). Inflammation may be one pathway through which SES influences health. Using 2658 participants in the Coronary Artery Risk Development in Young Adults (CARDIA) Study, we examine whether two measures of SES assessed at baseline (mean age, 32 ± 4 years)—years of education and household income—predict change in C-reactive protein (CRP) concentrations over the course of 13 years. We also examine whether four health-related behaviors—smoking, fruit and vegetable consumption, physical activity, and alcohol consumption—mediate the prospective association of SES with CRP. Both higher education and household income predicted smaller increases in CRP over the 13 years of follow-up independent of age, sex, race, CARDIA center, body mass, medical diagnoses, medications, and hormone use (among women). Associations did not differ by race or sex. When examined in separate analyses, smoking and fruit and vegetable intake each accounted for a significant proportion of the respective effects of education and household income on CRP change, and physical activity a significant proportion of the effect of household income. These findings suggest that poor health behaviors among persons of lower socioeconomic status can have long-term effects on inflammation.

Abstract from: Psychosomatic Medicine (2012), 74, 567-573.

Parenthood and Host Resistance to the Common Cold

Sneed, R., Cohen, S., Turner, R.B. & Doyle, W. J.

Objective: To determine whether parenthood predicts host resistance to the common cold among healthy volunteers experimentally exposed to a common cold virus. Methods: Participants were 795 healthy volunteers (age range = 18Y55 years) enrolled in one of three viral-challenge studies conducted from 1993 to 2004. After reporting parenthood status, participants were quarantined, administered nasal drops containing one of four common cold viruses, 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 to 6 days after exposure. All analyses included controls for immunity to the experimental virus (prechallenge specific antibody titers), viral strain, season, age, sex, race/ethnicity, marital status, body mass, study, employment status, and education. Results: Parents were less likely to develop colds than nonparents were (odds ratio [OR] = 0.48, 95% confidence interval [CI] = 0.31-0.73). This was true for both parents with one to two children (OR = 0.52, 95% CI = 0.33-0.83) and three or more children (OR = 0.39, 95% CI = 0.22-0.70). Parenthood was associated with a decreased risk of colds for both those with at least one child living at home (OR = 0.46, 95% CI = 0.24-0.87) and those whose children all lived away from home (OR = 0.27, 95% CI = 0.12-0.60). The relationship between parenthood and colds was not observed in parents aged 18 to 24 years but was pronounced among older parents. Conclusions: Parenthood was associated with greater host resistance to common cold viruses.

Abstract from: Health Psychology (2012), 31, 297-305.

Positive Emotion Word Use and Longevity in Famous Deceased Psychologists

Pressman, S. D. & Cohen, S.

Objective: This study examined whether specific types of positive and negative emotional words used in the autobiographies of well-known deceased psychologists were associated with longevity. Methods: For each of the 88 psychologists, the percent of emotional words used in writing was calculated and categorized by valence (positive or negative) and arousal (activated [e.g., lively, anxious] or not activated [e.g., calm, drowsy]) based on existing emotion scales and models of emotion categorization. Results: After controlling for sex, year of publication, health (based on disclosed illness in autobiography), native language, and year of birth, the use of more activated positive emotional words (e.g., lively, vigorous, attentive, humorous) was associated with increased longevity. Negative terms (e.g., angry, afraid, drowsy, sluggish) and unactivated positive terms (e.g., peaceful, calm) were not related to longevity. The association of activated positive emotions with longevity was also independent of words ind cative of social integration, optimism, and the other affect/activation categories. Conclusions: Results indicate that in writing, not every type of emotion correlates with longevity and that there may be value to considering different categories beyond emotional valence in health relevant outcomes.

Abstract from: Allergy (2012), 67, 545-551.

Prenatal Negative Life Events Increases Cord Blood IgE: Interactions with Dust Mite Allergen and Maternal Atopy

Peters, J. L., Cohen, S. Staudenmayer, J., Hosen, J., Platts-Mills, A. E., & Wright, R.

Background: Prenatal exposure to both stress and aeroallergens (dust mite) may modulate the fetal immune system. These exposures may interact to affect the newborn immune response. We examined associations between prenatal maternal stress and cord blood total IgE in 403 predominately low-income minority infants enrolled in the Asthma Coalition on Community, Environment, and Social Stress (ACCESS) project. We also examined potential modifying effects of maternal atopy and maternal dust mite exposure. Methods: The Crisis in Family Systems survey was administered to mothers prenatally, and a negative life event domain score was derived to characterize stress. Dust mite allergen was quantified in dust from pregnant mothers' bedrooms. Cord blood was analyzed for total IgE. Using linear regression, we modeled the relationship of stress with cord blood IgE and interactions of stress with dust mite and/or maternal atopy, adjusting for potential confounders. Results: Higher prenatal maternal stress (ß = 0.09; P = 0.01) was associated with increased cord blood IgE. The interactive effects between stress and dust mite groups (high vs low) were significantly different for children of atopic vs nonatopic mothers (P for three-way interaction = 0.005). Among children of atopic mothers, the positive association between stress and IgE was stronger in the high dust mite group. In children of mothers without a history of atopy, the positive association between stress and IgE was most evident in the low allergen group. Conclusions: Prenatal stress was independently associated with elevated cord blood IgE. Mechanisms underlying stress effects on fetal immunomodulation may differ based on maternal atopic status.

Abstract from: Proceedings of the National Academy of Sciences [USA] (2012), 109, 5995-5999.

Chronic Stress, Glucocorticoid Receptor Resistance, Inflammation, and Disease Risk

Cohen, S., Janicki-Deverts, D., Doyle, W. J., Miller, G. E., Frank, E., Rabin, B. S., & Turner, R. B.

We propose a model wherein chronic stress results in glucocorticoid receptor resistance (GCR) that, in turn, results in failure to downregulate 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-1beta, TNF-alpha, 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.

         Errata: Although the description in the text is correct, the titles of tables 1 and 2 are incorrect and misleading. They should read as follows:
                  Table 1. Simple effect associations of cortisol and lymphocyte subsets for subjects experiencing and not experiencing a stressful life event.
                  Table 2. Simple effect associations of cortisol and lymphocyte subsets for subject who did and did not develop a common cold.

Abstract from: Journal of Applied Social Psychology (2012), 42, 1320-1334.

Who's Stressed? Distributions of Psychological Stress in the United States in Probability Samples from 1983, 2006, and 2009

Carnegie Mellon University press release

Cohen, S., & Janicki-Deverts, D.

Psychological stress was assessed in 3 national surveys administered in 1983, 2006, and 2009. In all 3 surveys, stress was higher among women than men; and increased with decreasing age, education and income. Unemployed persons reported high levels of stress, while the retired reported low levels. All associations were independent of one another and of race/ethnicity. Although minorities generally reported more stress than whites, these differences lost significance when adjusted for the other demographics. Stress increased little in response to the 2008-2009 economic downturn, except among middle-aged, college-educated white men with full-time employment. These data suggest greater stress-related health risks among women, younger adults, those of lower socioeconomic status, and men potentially subject to substantial losses of income and wealth.

Abstract from: Journal of Allergy and Clinical Immunology (2011), 128, 337-345.

Associations Among Maternal Childhood Socioeconomic Status, Cord Blood IgE Levels, and Repeated Wheeze in Urban Children

Sternthal, M. J., Coull, B. A., Chiu, Y. H. M., Cohen, S., & Wright, R. J.

BACKGROUND: Independent of current socioeconomic status (SES), past maternal SES might influence asthma outcomes in children. OBJECTIVE: We examined associations among the mother’s SES
in the first 10 years of her life (maternal childhood SES), increased cord blood IgE levels (upper 20% [1.37 IU/mL]), and repeated wheeze (>/=2 episodes by age 2 years) in an urban pregnancy cohort (n = 5,510). METHODS: Data on sociodemographics, discrimination, financial strain, community violence, interpersonal trauma, and other negative events were obtained prenatally. Prenatal household dust was assayed for cockroach and murine allergens, and traffic-related air pollution was estimated by using spatiotemporal land-use regression. Maternal childhood SES was defined by parental home ownership (birth to 10 years). Maternally reported child wheeze was ascertained at 3-month intervals from birth. Using structural equation models, we examined whether outcomes were dependent on maternal
childhood SES directly versus indirect relationships operating through (1) cumulative SES-related adversities, (2) the mother’s socioeconomic trajectory (adult SES), and (3) current prenatal environmental exposures. RESULTS: Mothers were largely Hispanic (60%) or black (28%), 37% had not completed high school, and 56% reported parental home ownership. When associations between low maternal
childhood SES and repeated wheeze were examined, there were significant indirect effects operating through adult SES and prenatal cumulative stress (b = 0.28, P = .003) and pollution (b = 0.24, P = .004; P value for total indirect effects </= .04 for both pathways). Low maternal childhood SES was directly related to increased cord blood IgE levels (b = 0.21, P = .003). Maternal cumulative adversity (interpersonal trauma) was also associated with increased cord blood IgE levels (b = 0.19, P =.01), although this did not explain maternal childhood SES effects. CONCLUSION: Lower maternal childhood SES was associated with increased cord blood IgE levels and repeated wheeze through both direct and indirect effects, providing new insights into the role of social inequalities as determinants of childhood
respiratory risk.

Eighty-four healthy graduate participants were administered the standard course of 3 hepatitis B vaccinations. Five months after the first dose (shortly after the second injection), each participant completed psychosocial measures, and a blood sample was drawn for determination of hepatitis B surface antibody titer. After completion of the vaccination series, participants performed an acute stress protocol, consisting of a 30-min adaptation period and a 5-min evaluative speech task. Blood was drawn at the end of the resting and task periods for assessment of cellular immune measures. Lower antibody response, as assessed after the second hepatitis B injection, was predicted independently by (a) high trait negative affect and (b) diminished T-cell proliferation in response to PHA. These data provide evidence that trait negative affect and the magnitude of stress-induced suppression of immune function may have clinical significance.

Psychological Stress and Antibody Response to Immunization: A Critical Review of the Human Literature

Cohen, S., Miller, G.E., and Rabin, B.S.

Objective: To evaluate the evidence for the hypothesis that psychological stress influences antibody response to immunization in humans.

Methods: Critical review of the literature.

Results: The evidence supports an association between psychological stress and suppression of humoral immune (antibody) response to immunization. This association is convincing in the case of secondary immune response but weak for primary response. The lack of consistent evidence for a relation with primary response may be attributable to a failure to consider the critical point(s) when stress needs to be elevated in the course of the production of antibody. Lower secondary antibody responses were found among patients with chronically high levels of stress (severe enduring problems or high levels of trait negative affect). These responses were found most consistently among older adults. Lower secondary responses were also found for those reporting acute stress or negative affect, but only in studies of S-IgA antibody where psychological and antibody measures were linked very closely in time. Health practices did not mediate relations between stress and antibody responses, however, there were indications that elevated cortisol levels among stressed patients could play a role. Evidence also suggests the possible influences of dispositional stress-reactivity and low positive affect in the inhibition of antibody production.

Conclusions: The literature supports a relationship between psychological stress and antibody responses to immunizations. The data are convincing in the case of secondary response but weak for primary response. More attention to the kinetics of stress and antibody response and their interrelations is needed in future research.

Psychological Interventions and the Immune System: A Meta-Analytic Review and Critique

Miller, G.E., and Cohen, S.

This article reviews evidence for the hypothesis that psychological interventions can modulate the immune response in humans, and presents a series of models depicting the psychobiological pathways through which this might occur. Although more than eighty-five trials have been conducted, meta-analyses reveal only modest evidence that interventions can reliably alter immune parameters. The most consistent evidence emerges from hypnosis and conditioning trials. Disclosure and stress-management show scattered evidence of success. Relaxation demonstrates little capacity to elicit immune change. While these data provide only modest evidence of successful immune modulation, it would be premature to conclude that the immune system is unresponsive to psychological interventions. This literature has important conceptual and methodological issues that need to be resolved before any definitive conclusions can be reached.

The Stability of and Intercorrelations Among Cardiovascular, Immune, Endocrine, and Psychological Reactivity

Cohen, S., Hamrick, N., Rodriguez, M.S., Feldman, P.J., Rabin, B.S., and Manuck, S.B.

One hundred fifteen college students were exposed to an evaluative speech task twice, separated by two weeks. At both sessions, we assessed cardiovascular, endocrine, immune, and psychological response at baseline and during the task. We found stability across sessions for stress-induced increases in anxiety and task engagement, heart rate, blood pressure, norepinephrine (but not epinephrine), cortisol, natural killer cell cytotoxicity, and numbers of circulating CD3+, CD8+, and CD56+ (but not CD4+ or CD19+) lymphocytes. The stable cardiovascular, immune, and endocrine reactivities were intercollated, providing evidence of a unified physiological stress response across these outcomes. Although stable stress-induced increases in task engagement were associated with the physiological stress responses, stress-induced anxiety was not.

The Impact of Personality on the Reporting of Unfounded Symptoms and Illness

Feldman, P.J., Cohen, S., Doyle, W.J., Skoner, D.P., and Gwaltney, J.M.

We examined the role of personality in the reporting of symptoms and illness not supported by underlying pathology. After assessment of the "Big Five" personality factors, 276 healthy volunteers were inoculated with a common cold virus. On each of the following five days, we assessed objective indicators of pathology, self-reported symptoms, and self-reported illness onset. Neuroticism was directly associated with reports of unfounded (without a physiological basis) symptoms in individuals at baseline and post-inoculation in those with and without colds. Neuroticism was also indirectly associated with reports of unfounded illness through greater symptom reporting. Openness was associated with reporting unfounded symptoms in those with verifiable colds, while conscientiousness was associated with reporting unfounded illness in those who were not ill.

Feldman, P.J., Cohen, S., Lepore, S.J., Matthews, K.A., Kamarck, T.W., and Marsland, A.L.

One pathway through which stressors are thought to influence physiology is through their effects on emotion. We used meta-analytic statistical techniques with data from nine studies to test the effects of acute laboratory stressors (speech, star mirror-image tracing, handgrip) on emotional (undifferentiated negative emotion, anger, anxiety) and cardiovascular (CV) response. In all of the studies, participants responded to stressors with both increased CV response and increased negative emotion. Increases in negative emotion were associated with increases in CV response across tasks, however, these associations were small. The range of variance accounted for was between 2% and 12%. Thus, the contribution of negative emotion, as assessed in these studies, to physiological responses to acute laboratory stressors was limited. Although these results raise questions about the role of emotion in mediating stress-elicited physiological responses, the nature of the acute laboratory stress paradigm may contribute to the lack of a strong association.

Social Status and Susceptibility to Respiratory Infections

Cohen, S.

Adults and children of lower socioeconomic status (SES) are at higher risk for a wide range of communicable infectious diseases, especially respiratory infections. Greater risk for infectious illness among people with lower SES is thought to be attributable to increased exposure to infectious agents and decreased host resistance to infection. We summarize three studies that examine the prospective association of several markers of social status (unemployment, perceived and observed social status) with host resistance to upper respiratory infections. Unemployment was associated with increased susceptibility to infection in adult humans. Lower social status in male monkeys was also associated with increased susceptibility, as was lower perceived social status in humans. The association of social status and susceptibility was accounted for primarily by increased risk in the lowest social status groups. However, further increases in social status were associated with further decreases in susceptibility in both monkeys and humans.

Psychological Stress, Cytokine Production and Severity of Upper Respiratory Illness

Cohen, S., Doyle, W. J., and Skoner, D. P.

Objective: To assess the role of psychological stress in the expression of illness among infected subjects and test the plausibility of local pro-inflammatory cytokine production as a pathway linking stress to illness.

Methods: After completing a measure of psychological stress, 55 subjects were experimentally infected with an influenza A virus. Subjects were monitored in quarantine daily for upper respiratory symptoms, mucus production, and nasal lavage levels of interleukin (IL) 6.

Results: Higher psychological stress assessed prior to the viral challenge was associated with greater symptom scores, greater mucus weights, and higher IL-6 lavage concentrations in response to infection. The IL-6 response was temporally related to the two markers of illness severity, and mediation analyses indicated that these data were consistent with IL-6 acting as a major pathway through which stress was associated with increased symptoms of illness. However, this pattern of data is also consistent with rises in IL-6 occurring in response to tissue damage associated with illness symptoms.

Conclusions: Psychological stress predicts a greater expression of illness and an increased production of IL-6 in response to an upper respiratory infection.

Pathways Linking Major Depression and Immunity in Ambulatory Female Patients

Miller, G. E., Cohen, S., and Herbert, Tracy B.

Objective: The goals of this study were to investigate whether depression is associated with cellular immunity in ambulatory patients and to identify neuroendocrine and behavioral pathways that might account for this relationship. Method: We studied 32 women who met DSM-IV criteria for Major Depressive Disorder and 32 healthy female control subjects. The groups were matched on age and ethnicity. All were unmedicated and free of disease involving the immune system. Results: Depressed subjects had reduced proliferative responses to the mitogens ConA and PHA compared to controls. Natural killer cell activity was reduced among older depressed subjects but enhanced among younger depressed subjects. Although depression was associated with elevated circulating levels of norepinephrine and estradiol, these hormones could not account for the immunologic differences between depressed and control subjects. Depression was also associated with greater tobacco and caffeine consumption, less physical activity, and poorer sleep quality. Mediational analyses were consistent with physical activity acting as a pathway through which depression was associated with reduced lymphocyte proliferation. Conclusions: Ambulatory patients with mild to moderately severe depression exhibit reduced mitogen-stimulated lymphocyte proliferative responses and altered natural killer cell cytotoxicity. The relationship between depression and proliferative responses may be mediated by physical activity.

Cohen, S., Doyle, W. J., Skoner, D. P., Rabin, B. S., and Gwaltney, J. M.
 
Objective: To examine the hypothesis that diverse ties to friends, family, work, and community are associated with increased host resistance to infection.

Design:  After reporting the extent of  participation in 12 types of social ties (e.g., spouse, parent, friend, workmate, member of social group), subjects were given nasal drops containing one of two rhinoviruses, and monitored for the development of  a common cold.

Setting:  Quarantine.

Participants:  276 healthy volunteers, ages 18-55, neither HIV positive nor pregnant.

Outcome Measures: Colds (illness in the presence of a verified infection), mucus production, mucociliary clearance function, and amount of viral replication.

Results:  In response to both viruses, those with more types of social ties were less susceptible to common colds, shed less virus, produced less mucus, and were more effective in ciliary clearance of their nasal passages.  These relations were unaltered by statistical controls for pre-challenge virus-specific antibody, virus-type, age, gender, season, body mass, education, and race.   Susceptibility to colds decreased in a dose-response manner with increased diversity of the social network.  There was an adjusted relative risk of 4.2 comparing persons with fewest (1-3) to those with most (6 or more) types of social ties.  Although smoking, poor sleep quality, alcohol abstinence, low dietary intake of vitamin C, elevated catecholamine levels, and being introverted were all associated with greater susceptibility to colds, they could only partially account for the relation between social network diversity and incidence of colds.

Conclusions: More diverse social networks were associated with greater resistance to upper respiratory illness.
 

Types of Stressors That Increase Susceptibility to the Common Cold in Healthy Adults

Cohen, S., Frank, E., Doyle, W. J., Skoner, D. P., Rabin, B. S., and Gwaltney, J.

Two-hundred seventy-six volunteers completed a life stressor interview and psychological questionnaires and provided blood and urine samples.  They were then inoculated with common cold viruses and monitored for the onset of disease.  Although severe acute stressful life events (less than 1 month long) were not associated with developing colds, severe severe chronic stressors (1 month or longer) were associated with a substantial increase in risk of disease.  This relation was attributable primarily to under- or unemployment and to enduring interpersonal difficulties with family or friends.  The association between chronic stressors and susceptibility to colds could not be fully explained by differences among stressed and nonstressed persons in social network characteristics, personality, health practices, or prechallenge endocrine or immune measures.
 
 Updated April 8, 2013