Theodore F. Robles

Psychoneuroimmunology: Psychological influences on immune function and health

This review focuses on human psychoneuroimmunology studies published in the past decade. Issues discussed include the routes through which psychological factors influence immune function, how a stressors duration may influence the changes observed, individual difference variables, the ability of interventions to modulate immune function, and the health consequences of psychosocially mediated immune dysregulation. The importance of negative affect and supportive personal relationships are highlighted. Recent data suggest that immune dysregulation may be one core mechanism for a spectrum of conditions associated with aging, including cardiovascular disease, osteoporosis, arthritis, Type 2 diabetes, certain cancers, and frailty and functional decline; production of proinflammatory cytokines that influence these and other conditions can be stimulated directly by negative emotions and indirectly by prolonged infection.

The physiology of marriage: pathways to health

Marriage is the central relationship for most adults and has beneficial effects for health. At the same time, troubled marriages have negative health consequences. This review outlines the physiological pathways through which marital relationships influence health based on a stress/social support model. In addition, we review recent findings suggesting that unhappy marriages are associated with morbidity and mortality. We then turn to studies of marital interaction that include assessment of physiological pathways through which marital functioning influences health: the cardiovascular, endocrine, and immune systems. Across these studies, negative and hostile behaviors during marital conflict discussions are related to elevations in cardiovascular activity, alterations in hormones related to stress, and dysregulation of immune function. Using recent conceptualizations of the physiological impact of chronic stress, we illustrate how physiological changes associated with marital functioning in these studies have long-term implications for health outcomes. Finally, we discuss future implications of current research for understanding the relationships among marital functioning, physiology, and health.

Psychoneuroimmunology and psychosomatic medicine: Back to the future.

Objective Although psychological modulation of immune function is now a well-established phenomenon, much of the relevant literature has been published within the last decade. This article speculates on future directions for psychoneuroimmunology research, after reviewing the history of the field. Methods This review focuses on human psychoneuroimmunology studies published since 1939, particularly those that have appeared in Psychosomatic Medicine. Studies were clustered according to key themes, including stressor duration and characteristics (laboratory stressors, time-limited naturalistic stressors, or chronic stress), as well as the influences of psychopathology, personality, and interpersonal relationships; the responsiveness of the immune system to behavioral interventions is also addressed. Additionally, we describe trends in populations studied and the changing nature of immunological assessments. The final section focuses on health outcomes and future directions for the field. Results There are now sufficient data to conclude that immune modulation by psychosocial stressors or interventions can lead to actual health changes, with the strongest direct evidence to date in infectious disease and wound healing. Furthermore, recent medical literature has highlighted a spectrum of diseases whose onset and course may be influenced by proinflammatory cytokines, from cardiovascular disease to frailty and functional decline; proinflammatory cytokine production can be directly stimulated by negative emotions and stressful experiences and indirectly stimulated by chronic or recurring infections. Accordingly, distress-related immune dysregulation may be one core mechanism behind a diverse set of health risks associated with negative emotions. Conclusions We suggest that psychoneuroimmunology may have broad implications for the basic biological sciences and medicine.

Marital quality and health: A meta-analytic review

This meta-analysis reviewed 126 published empirical articles over the past 50 years describing associations between marital relationship quality and physical health in more than 72,000 individuals. Health outcomes included clinical endpoints (objective assessments of function, disease severity, and mortality; subjective health assessments) and surrogate endpoints (biological markers that substitute for clinical endpoints, such as blood pressure). Biological mediators included cardiovascular reactivity and hypothalamic-pituitary-adrenal axis activity. Greater marital quality was related to better health, with mean effect sizes from r = .07 to .21, including lower risk of mortality (r = .11) and lower cardiovascular reactivity during marital conflict (r = -.13), but not daily cortisol slopes or cortisol reactivity during conflict. The small effect sizes were similar in magnitude to previously found associations between health behaviors (e.g., diet) and health outcomes. Effect sizes for a small subset of clinical outcomes were susceptible to publication bias. In some studies, effect sizes remained significant after accounting for confounds such as age and socioeconomic status. Studies with a higher proportion of women in the sample demonstrated larger effect sizes, but we found little evidence for gender differences in studies that explicitly tested gender moderation, with the exception of surrogate endpoint studies. Our conclusions are limited by small numbers of studies for specific health outcomes, unexplained heterogeneity, and designs that limit causal inferences. These findings highlight the need to explicitly test affective, health behavior, and biological mechanisms in future research, and focus on moderating factors that may alter the relationship between marital quality and health.

To assess, to control, to exclude: Effects of biobehavioral factors on circulating inflammatory markers☆

Behavioral scientists have increasingly included inflammatory biology as mechanisms in their investigation of psychosocial dynamics on the pathobiology of disease. However, a lack of standardization of inclusion and exclusion criteria and assessment of relevant control variables impacts the interpretation of these studies. The present paper reviews and discusses human biobehavioral factors that can affect the measurement of circulating markers of inflammation. Keywords relevant to inflammatory biology and biobehavioral factors were searched through PubMed. Age, sex, and hormonal status, socioeconomic status, ethnicity and race, body mass index, exercise, diet, caffeine, smoking, alcohol, sleep disruption, antidepressants, aspirin, and medications for cardiovascular disease are all reviewed. A tiered set of recommendations as to whether each variable should be assessed, controlled for, or used as an exclusion criteria is provided. These recommendations provide a framework for observational and intervention studies investigating linkages between psychosocial and behavioral factors and inflammation.

Out of Balance A New Look at Chronic Stress, Depression, and Immunity

Chronic stress is typically associated with suppression of the immune system, including impaired responses to infectious disease and delayed wound healing. Recent work suggests that stress and depression can enhance production of proinflammatory cytokines, substances that regulate the bodys immune response to infection and injury. We provide a broad framework relating stress and depression to a range of diseases whose onset and course may be influenced by proinflammatory cytokines, particularly the cytokine interleukin-6 (IL-6). IL-6 has been linked to a spectrum of chronic diseases associated with aging. Production of proinflammatory cytokines that influence these and other conditions can be directly stimulated by chronic stress and depression. We suggest that a key pathway through which chronic stress and depression influence health outcomes involves proinflammatory cytokines. We discuss the evidence for relationships between psychosocial factors and proinflammatory cytokines, and important health implications of these findings.

Stress, social support, and delayed skin barrier recovery.

Objective: To examine the effect of a brief laboratory stressor and social support before the stressor on cardiovascular and cortisol responses, and skin barrier recovery after skin disruption. Methods: Eighty-five healthy participants (mean age 22.9 ± 4.4 years) underwent a “tape-stripping” procedure that disrupts normal skin barrier function, and were randomly assigned to a No Stress (reading task), Stress (Trier Social Stress Test), or Stress + Social Support condition (support from a confederate before the stressor). Skin barrier recovery was assessed by measuring transepidermal water loss from up to 2 hours after skin disruption. Results: Compared with the No Stress condition, the stressor delayed skin barrier recovery by 10% at 2 hours after skin disruption (effect size, r = .29), and increased anxiety (r = .24), negative affect (r = .22), cardiovascular activity (r values from .4–.6), and among male participants, cortisol levels (r = .40). Social support did not influence psychological or physiological responses or skin barrier recovery. Larger physiological responses to the tasks did not predict slower skin barrier recovery. Instead, larger systolic blood pressure responses predicted faster skin barrier recovery (r = .26). Conclusions: This study replicated the effects of short-term laboratory stressors on skin barrier recovery, further establishing the relevance of skin barrier recovery for future research. The support manipulation did not influence physiological responses or skin barrier recovery, suggesting that future research on social support, physiology, and objective health outcomes should focus on naturalistic social interactions, relationships, and stressors. AUCI = area under the curve with respect to increase; BMI = body mass index; DBP = diastolic blood pressure; GCRC = General Clinical Research Center; HR = heart rate; MAP = mean arterial pressure; SBP = systolic blood pressure; TSST = Trier Social Stress Test; TEWL = transepidermal water loss.

Preschoolers' everyday conflict at home and diurnal cortisol patterns.

OBJECTIVE Early life family conflict is associated with physical health problems later in life, but little is known about the biological pathways through which conflict at home exerts it deleterious effects on health. The goal of this study was to investigate the associations between naturalistically assessed conflict in everyday family environments and diurnal cortisol in preschool-aged children. DESIGN Forty-four children aged 3-5 from two-parent families provided six saliva samples per day over 2 days from a Saturday morning through Sunday night. For a full day on either Saturday or Sunday, children wore a child version of the Electronically Activated Recorder, a digital voice recorder that records ambient sounds while participants go about their daily lives. Parents provided reports of child externalizing behaviors as well as daily reports of child conflicts. MAIN OUTCOME MEASURES Diurnal salivary cortisol over the two weekend days of the study. RESULTS Greater Electronically Activated Recorder-assessed child conflict at home was associated with children having lower cortisol at wakeup (p < .009) and flatter diurnal cortisol slopes (p < .007). These associations remained significant even after controlling for parent reports of child externalizing behaviors, parent reports of daily child conflicts, and child age and sex. CONCLUSION These findings indicate that taking into consideration everyday conflicts at home may be key to our understanding of stress-health links in young children.

Examining psychosocial factors related to cancer incidence and progression: In search of the silver lining

11 The possibility of links between psychosocial factors 12 and cancer incidence and progression have generated 13 considerable scientific and public interest. As early as the 14 mid-1920 s, psychologists were speculating about psy15 chogenic influences on cancer (Evans, 1926), and, for 16 decades, personality and individual differences have 17 been hypothesized as both etiologic and prognostic de18 terminants of cancer development (Brown, 1966; Ey19 senck, 2000; Fox, 1983). 20 With advances in psychoneuroimmunology have 21 come challenges to earlier theories addressing these links 22 (Fox, 1983; Kiecolt-Glaser & Chee, 1991). Biopsycho23 oncological researchers now emphasize the crucial role 24 of both the endocrine and immune systems in cancer 25 outcomes, and stress-associated dysregulation of bio26 logical and physiological processes have been high27 lighted. Unfortunately, this inquiry has been fraught 28 with methodological and conceptual hurdles that cloud 29 any concrete understanding about these potentially im30 portant linkages. We believe there is a silver lining be31 hind this cloud. As Segerstrom (this issue) and others 32 (Brown, 1966; Garssen & Goodkin, 1999) have indi33 cated, heterogeneous sampling and measurement have 34 produced divergent findings concerning the psychoso35 cial-cancer link. Notably, the relevance and validity of 36 the immunological and psychological assessments used 37 within cancer contexts have received little attention. 38 These are remediable weaknesses. Here, we highlight 39 some methodological points related to contextual spec40 ificity that should be considered seriously in psycho41 neuroimmunological studies of individual differences 42 and cancer outcomes. 43 Psychoneuroimmunology research on psychosocial 44 modifiers of stress responses and cancer processes have 45 primarily focused on nonspecific immune responses, in46 cluding NK cell function, mitogen stimulation of pe47 ripheral blood lymphocytes, and subsequent cytokine 48 production (Kiecolt-Glaser & Glaser, 1999).The rapid 49 methodological advancements in immunological, cellular 50 and molecular assaying techniques permit psychoneu51 roimmunological researchers to examine extraordinarily 52 micro-level physiological and biological processes. Im53 portantly, this technology affords examination of specific, 54 cancer-related mechanisms. 55 A potentially productive research focus for psycho56 social oncology is the study of stress effects on cellular 57 processes. Many carcinogens appear to induce tumors 58 by damaging cellular DNA and producing abnormal 59 cells (Fox, 1978; Setlow, 1978; Tomei, Kiecolt-Glaser, 60 Kennedy, & Glaser, 1990). The body s defenses against 61 this process include enzymes that destroy chemical car62 cinogens, processes for repairing damaged cellular 63 DNA, and the destruction of abnormal cells via apop64 tosis, a process of genetically programmed alterations in 65 cell structure that leads to failure of proliferation and 66 differentiation, and eventual cell suicide (Fox, 1978; 67 Tomei et al., 1990). Stress can alter each line of defense. 68 First, levels of methyltransferase, an important DNA 69 repair enzyme induced in response to carcinogen dam70 age, were significantly lower in stressed rats spleenic 71 lymphocytes compared to nonstressed controls (Glaser, Brain, Behavior, and Immunity xxx (2002) xxx–xxx

Developmental validation of a point-of-care, salivary α-amylase biosensor.

The translation of salivary alpha-amylase (sAA) to the ambulatory assessment of stress hinges on the development of technologies capable of speedy and accurate reporting of sAA levels. Here, we describe the developmental validation and usability testing of a point-of-care, colorimetric, sAA biosensor. A disposable test strip allows for streamlined sample collection and a corresponding hand-held reader with integrated analytic capabilities permits rapid analysis and reporting of sAA levels. Bioanalytical validation utilizing saliva samples from 20 normal subjects indicates that, within the biosensors linear range (10-230 U/ml), its accuracy (R(2)=0.989), precision (CV<9%), and measurement repeatability (range -3.1% to +3.1%) approach more elaborate laboratory-based, clinical analyzers. The truncated sampling-reporting cycle (<1 min) and the excellent performance characteristics of the biosensor has the potential to take sAA analysis out of the realm of dedicated, centralized laboratories and facilitate future sAA biomarker qualification studies.