Stress, emotion, and human immune function

This article provides a review of empirical evidence linking emotional processes to immune function in humans. Acute stressors have produced mixed effects on immunity, presumably through differential activation of physiological stress systems. Chronic stress has been associated with suppression of immune function, and there is evidence that the immune system may not adapt over time. Effects of stress accompanying social disruption and psychological depression, when demonstrated, have been consistently adverse. Certain personality styles may enhance or degrade immune response. Relationships between psychosocial factors and immunity have been identified for several diseases, including cancer, acquired immune deficiency syndrome, and autoimmune diseases; psychosocial interventions have been tested with variable results. Theoretical and methodological considerations are summarized and directions for future research suggested.     

Theory-Driven Interventions in Psychoneuroimmunology and HIV-1 Infection

Psychoneuroimmunology (PNI) is a rapidly evolving multidisciplinary field founded on the premise that psychosocial factors, the central nervous system, and the immune system are intimately linked. Following publication of scientific evidence supporting this link, a number of animal and human studies have been published, both inside and outside the area of human immunodeficiency virus (HIV) infection and acquired immunodeficiency syndrome. These studies support the existence of bidirectional feedback mechanisms operating between the brain and the immune system. To date, however, there is no all-encompassing model that predicts individual differences in the relationship among psychosocial factors, immunologic measures, and clinical disease progression in HIV type 1 (HIV-1) infection. This variability in human response has been explained by a number of cofactors (host as well as environmental) that appear to accelerate the course of the disease. Since psychosocial factors are highly amenable to behavioral interventions, several models for intervention research have been proposed to evaluate whether such interventions can enhance immune functioning, thereby curtailing disease progression. Examination of these interventions in the context of PNI and HIV-1 infection, however, is rather limited. Therefore, researchers and clinicians must not only consider conceptualizations and paradigms in this area of research, but also focus on empirically testable, theory-driven models that allow for the unique characteristics of individual patients.     

Psychosocial correlates of immune status and disease progression in HIV-1 infected homosexual men: Review of preliminary findings,and commentary

Abstract

Behavioral factors may have an effect on the course of infection in HIV-1 infected individuals. These effects can be mediated by the immune system of the host, which, based on psychoneuroimmunologic findings, can be affected by some psychosocial factors. We present a short review of some putative psychoneuroimmunologic pathways and their possible implications for HIV-1 infected individuals. We next summarize the findings of recent psychoimmunological work with HIV-1 seropositives and discuss the methodological problems in studying the psychoneuroimmunologic aspects of HIV-1 infection. Psychoneuroimmunologic research in HIV-1 seropositives is a rapidly developing field, yielding contradictory findings so far, but which in the long run could provide important knowledge for psychoimmunologic interventions, targeted at improving or preserving immune status and retarding disease progression, as well as optimizing psychosocial functioning.     

Stress management and psychoneuroimmunology in HIV infection

Does stress management affect psychological and immune functioning in persons with human immunodeficiency virus infections? Stress-management techniques, such as relaxation training and imagery, cognitive restructuring, coping-skills training, and interpersonal-skills training, may reduce anxiety, depression, and social isolation in HIV-infected persons by lowering physical tension and increasing a sense of control and self-efficacy. A psychoneuroimmunologic model is proposed wherein these psychological changes are hypothesized to be accompanied by an improved ability to regulate neuroendocrine functioning, which in turn may be associated with a partial normalization of immune system functions such as lymphocyte proliferation and cytotoxicity, providing more efficient surveillance of latent viruses that may contribute directly to increased HIV replication and generate opportunistic infections or cancer if left unchecked. Such a normalization of stress-associated immune system decrements are hypothesized to forestall or minimize increases in viral load and expression of clinical symptoms. This model is useful for testing the factors contributing to the health effects of stress-management interventions in HIV-infected persons. In this context, one general research strategy for testing the effects of stress-management interventions is to target them toward the more prevalent psychosocial challenges that HIV-infected people face at various points in the disease process; enroll an HIV-infected population (eg, HIV-positive homosexual and bisexual men) into a randomized trial; and monitor changes in cognitive, affective, behavioral, and social factors in parallel with hormonal, immunologic, viral, and clinical changes over the course of time. This article will review the major psychoneuroimmunologic findings that have emerged using this paradigm and suggest future research directions and clinical applications.     

Psychosocial risk factors, natural immunity, and cancer progression: Implications for intervention

One of the more important and emerging fields in which psychologists collaborate with other disciplines is psychoimmunology. Centuries of clinical anecdote and decades of psychosomatic hypotheses have gained credibility in the eyes of the medical establishment—and many patients—by the systematic investigation of mechanisms potentially explaining how events intrapsychic and interpersonal could affect physical disease processes. The central nervous system is connected with the immune system by both neuronal and endocrinological pathways. The immune system has been found to mediate the organism’s response to aberrations of its own normal functions, as well as to invading organisms from without. AIDS, arthritis, asthma, lupus, and herpes are some of the illnesses in which research is demonstrating important relationships among psychosocial and immunological factors and disease course. In this article, we first discuss the immunological apparatus in order to provide a base for subsequent discussions of the effects of stress on immune function. Then we discuss malignant diseases and current evidence that disease course is related to both psychosocial stressors and immune function. We next discuss a model of these interactions, and finally we talk about interventions incorporating psychosocial factors aimed at influencing immune status and, thus, disease course.     

Chronic restraint stress impairs T-cell immunity and promotes tumor progression in mice

Long-term exposure to stressful situations can affect the immune system. The T-cell response is an important component of anti-tumoral immunity. Hence, impairment of the immune function induced by a chronic stressor has been postulated to alter the immunosurveillance of tumors, thus leading to a worse neoplastic prognosis. Here, we show that chronic restraint stress affects T-cell mediated immunity in mice. This was evidenced by a decrease of mitogen-induced T-cell proliferation, a reduction in CD4(+)T lymphocyte number and a decrease of tumor necrosis factor-alpha (TNF-alpha) and Interferon-gamma (IFN-gamma) production in stressed mice. Additionally, mice subjected to chronic restraint stress displayed an enhancement of tumor growth in a syngeneic lymphoma model, i.e. an increase of tumor proliferation and a reduction of animal survival. Finally, stressed mice had a reduced specific cytotoxic response against these tumor cells. These results suggest that chronic exposure to stress promotes cancer establishment and subsequent progression, probably by depressing T-cell mediated immunity. The T-cell immunity impairment as well as the tumor progression enhancement emphasize the importance of the therapeutic management of stress to improve the prognosis of cancer patients.     

人格特质对个体心理性应激反应的调节作用

心理性应激是个体的内稳态受到社会心理威胁时候的状态。面对急性心理性应激源, 有机体的各大机能系统, 包括神经内分泌系统、免疫系统以及自主神经系统等, 会出现一系列生物功能的改变。已有研究表明人格特质(如自尊、特质焦虑和大五人格)会影响个体在心理性应激情境中的反应差异且影响方式尚不统一, 并且不同文化环境下人格特质影响心理性应激反应的方式是不一样的, 然而这种结果的差异有可能是生物标记物的不一致造成的, 也有可能是心理性应激任务的不一致造成的, 不能直接进行比较。未来研究应该在控制这些无关变量的基础上, 从跨文化的角度去考察人格特质对个体心理性应激反应差异的影响。     

应当重视肿瘤微环境中外因的研究

长期以来,肿瘤学的几乎所有研究一直在关注肿瘤细胞本身,从哲学角度看这无疑是正确的。肿瘤细胞是肿瘤事件发生发展的内因。近年研究表明,肿瘤的外因,即肿瘤微环境中的非肿瘤细胞及其产物,对肿瘤的发生发展起着十分重要的作用。肿瘤微环境的外因,通过作用于内因选择了更具抵抗性的肿瘤细胞,促进了肿瘤的进展与转移。因此,重视肿瘤微环境的外因研究,对肿瘤治疗学将会开辟以外因为靶点干预的新思路。     

Restorative biological processes and health

Research on psychological influences on physiology primarily focuses on biological responses during stressful challenges, and how those responses can become dysregulated with prolonged or repeated exposure to stressful circumstances. At the same time, humans spend considerable time recovering from those challenges, and a host of biological processes involved in restoration and repair take place during normal, non-stressed activities. We review restorative biological processes and evidence for links between psychosocial factors and several restorative processes including sleep, wound healing, antioxidant production, DNA repair, and telomerase function. Across these biological processes, a growing body of evidence suggests that experiencing negative emotional states, including acute and chronic stress, depressive symptoms, and individual differences in negative affectivity and hostility, can influence these restorative processes. This review calls attention to restorative processes as fruitful mechanisms and outcomes for future biobehavioral research.     

The effects of stressful life events,coping, and cortisol on HIV infection

What is the role of stress and coping in changes in immunologic and clinical indicators of human immunodeficiency virus disease progression? There is substantial evidence that stressful life events and passive coping strategies, such as denial, may have a detrimental effect on HIV disease progression. Given the harmful effects of stress and passive coping, the author reviews the limited research testing the efficacy of interventions, such as cognitive-behavioral therapies for HIV-infected persons. Finally, in trying to understand psychoimmune relationships in HIV, the evidence is examined for the mediating and direct effects of cortisol, a hormone associated with stress, on HIV disease progression. Delineating the role of psychosocial factors and cortisol on HIV disease progression may aid in the development of new interventions for this devastating disease.     

肿瘤疫苗治疗肿瘤的前景

肿瘤疫苗的发展已经历了一个多世纪,20世纪50年代,人们开始了自体肿瘤疫苗的研究.使肿瘤疫苗(主动性免疫治疗)成为继手术、放疗、化疗之后的肿瘤治疗方法.肿瘤疫苗作为主动特异性免疫治疗,在临床中起到越来越重要的作用,人们开始尝试利用多种方法制备肿瘤疫苗并利用其促进机体免疫应答,从整体细胞,分子水平调控机体对肿瘤的免疫.目前肿瘤疫苗的研制已取得很大进展,给人类战胜肿瘤提供很大希望。     

心理神经免疫学研究

心理神经免疫学（Psychoneuroimmunology）是一门探索人类心身健康奥秘的新型边缘学科。它研究神经系统如何将心理因素转换为可以影响健康的生理状态的机制,特别是脑和行为如何影响免疫系统,又如何受到免疫系统的影响的。免疫系统和神经系统之间是否真正存在联系一直有争论,我们实验室围绕高级神经活动对免疫系统的作用开展了研究。工作包括：条件反射性免疫抑制和增强、情绪应激与免疫、心理行为干预与癌症等。这些工作不仅证实了心理调控,比如信号刺激、情绪和意念想象等,确实可以影响免疫系统的功能,而且对有关机制进行了探讨     

Functional neuroimaging of working memory in survivors of childhood brain tumors and healthy children: Associations with coping and psychosocial outcomes

Purpose: Pediatric brain tumors are the second most common cancer diagnosis in individuals under age 20 and research has documented significant neurocognitive, psychosocial, and emotional late effects. Associations among these deficits have not been adequately considered and the role of survivors’ coping with stress in relation to deficits is unknown. Further, research has yet to examine neurobiological processes related to neurocognitive, psychosocial, and emotional difficulties in survivors through the use of functional neuroimaging. Method: Questionnaire measures and functional neuroimaging were used to examine the neurocognitive, psychosocial, and emotional functioning and coping responses of survivors of pediatric brain tumors (N = 17; age 8–16) and healthy children (N = 15). Results: Survivors experienced elevated levels of psychosocial and behavioral/emotional difficulties relative to healthy controls and normative data. Increases in brain activation in prefrontal and other anterior regions in response to a working memory task were associated with better psychosocial functioning, use of engagement coping strategies, and less use of disengagement coping strategies. Regression analyses suggest coping accounts for a significant portion of the association between brain activation and behavioral/emotional functioning. Conclusions: This study extends late-effects research by examining neurobiological processes associated with psychosocial and emotional difficulties. These findings contribute to our understanding of difficulties in survivors and provide a foundation for research exploring these associations and mediators of deficits in future longitudinal studies.     

Effects of mental stressors on mitogen induced lymphocyte responses in the laboratory

Abstract

There is considerable evidence from naturalistic studies that psychosocial stressors affect human immune function. To achieve control over factors that could bias naturalistic studies, laboratory stressors developed by cardiovascular researchers were tested to determine if they affected immune function. Thirty volunteer students were exposed to 20 minutes of mental tasks. Psychophysiological indices (heart rate, blood pressure, skin conductance) and subjective responses were monitored prior to, during, and 1-hour after the tasks, blood, samples for immunological analyses were also drawn at these times. Thirteen subjects who were not exposed to the tasks served as controls. Subjects exposed to the tasks showed increased levels of subjective distress and increased psychophysiologic responses (except diastolic blood pressure) during the tasks. Relative to controls, stressed subjects had reduced lymphocyte proliferative responses to classic T cell mitogens both immediately after and 1-hour after the tasks were found in whole blood cultures, although responses of isolated lymphocytes were not significantly affected. There were only marginal differences in whole blood mitogen responses for stressed subjects with low versus high autonomic reactions to the stressor. These results support an emerging view that the immune system is sensitive to brief stressors and that laboratory models may be useful for exploring stress-induced changes in immune function.     

民族冲突的社会心理机制

民族冲突是影响社会和谐与稳定的重大现实问题, 其社会心理机制是尚未解决的重要科学问题。本项目拟以我国西部地区藏族为例, 纳入社会威胁情境因素, 并整合社会认同理论和社会类别的心理本质论框架下的群际冲突研究。其基本理论命题是：民族冲突形成并不是单一因素所致, 而是基于个体层面、群体层面和社会情境层面的多水平变量相互作用的结果。本项目拟通过既相对独立又彼此关联的三个实证研究, 旨在考察少数民族关于“民族”的心理本质论对民族冲突的预测和影响作用, 探索民族身份延伸和社会威胁情境在其中的影响作用, 从而揭示民族冲突形成的社会心理机制, 旨在为构建民族冲突的预警机制模型奠定基础, 为跨越民族界限、实现多民族和谐共处和完善民族政策提供科学依据。     

A Psychoneuroimmunologic Perspective on AIDS Research: Questions,Preliminary Findings,and Suggestions1

Starting with the premise that research questions emanating from the fields of psychoneuroimmunology and behavioral medicine may provide critical information for understanding and treating acquired immune deficiency syndrome (AIDS), we provide brief backgrounds on psychoneuroimmunology and on AIDS. Previously, Solomon had generated 25 hypotheses based on the thesis that the immune and central nervous systems are intimately linked. Eight hypotheses from his list are presented as particularly relevant to AIDS. From these hypotheses, we derived a set of 12 new questions to be addressed in research on AIDS. Evidence and illustrations from studies in the literature, from our own research on psychoimmunologic relationships and psychosocial factors related to outcome, and from clinical examples is discussed for each question. Finally, suggestions are offered to address some of the problems in conducting psychoneurologic research.     

Predicting posttraumatic growth in breast cancer survivors.

Wide variability exists with respect to how breast cancer survivors respond to common psychological and psychosocial challenges of their disease, ranging from posttraumatic stress disorder to posttraumatic growth. This cross-sectional study examined contextual, disease-related, and intraindividual predictors of posttraumatic growth in 224 randomly selected breast cancer survivors. A series of hierarchical regression analyses found that age at diagnosis, marital status, employment, education, perceived intensity of disease, and active coping accounted for 34%, 35%, and 28% of the variance in growth in relationships with others, new possibilities, and appreciation for life. These findings suggest that a more comprehensive model of growth will be helpful in understanding the various factors that play a role in breast cancer survivors' perception of psychological and psychosocial growth.     

The Impact of Cancer on Psychological and Social Outcomes

Cancer is now the biggest cause of mortality worldwide. Although the debilitating physical symptoms of cancer have long been known, the psychological and social impacts of cancer have become the subject of examination only relatively recently. The psychological outcomes that have been examined are primarily negative emotional variables, e.g., anxiety, but emerging research has focused on positive emotional variables, e.g., post‐traumatic growth, or cognitive outcomes. In this article, we provide a synthesis of reviews that have addressed the psychosocial impact of cancer. The framework for this synthesis is provided by a conceptualisation in which the presence of cancer impacts on psychosocial outcomes either directly or via mediating variables, including physical symptoms and treatment, and that this effect may be moderated by several variables, some characteristic of the person with cancer (demographic or personality‐related variables) and some characteristic of their environment (social support and medical variables). We also briefly examine the impact of cancer on the broader family unit following cancer diagnosis, treatment, survivorship and bereavement. We conclude that the heterogeneity of the cancer experience highlights the need for theoretically driven research and consistency in measurement approaches to determine mechanisms by which cancer exerts influence on psychosocial outcomes. This would allow development and delivery of targeted psychological interventions and a clearer delineation of the roles of the various parties, including clinical psychologists, family members and policymakers.     

Neural bases of moderation of cortisol stress responses by psychosocial resources

Psychosocial resources have been tied to lower psychological and biological responses to stress. The present research replicated this relationship and extended it by examining how differences in dispositional reactivity of certain neural structures may underlie this relationship. Two hypotheses were examined: (a) psychosocial resources are tied to decreased sensitivity to threat and/or (b) psychosocial resources are associated with enhanced prefrontal inhibition of threat responses during threat regulation. Results indicated that participants with greater psychosocial resources exhibited significantly less cortisol reactivity following a stress task, as predicted. Analyses using functional magnetic resonance imaging revealed that psychosocial resources were associated with greater right ventrolateral prefrontal cortex and less amygdala activity during a threat regulation task but were not associated with less amygdala activity during a threat sensitivity task. Mediational analyses suggest that the relation of psychosocial resources to low cortisol reactivity was mediated by lower amygdala activity during threat regulation. Results suggest that psychosocial resources are associated with lower cortisol responses to stress by means of enhanced inhibition of threat responses during threat regulation, rather than by decreased sensitivity to threat.     

心理社会应激的免疫反应规律与机制

心理社会应激会引起免疫系统发生免疫防御、免疫自稳和免疫监视方面的功能变化, 并随着应激刺激的时间和强度的变化而发生着异常与正常之间的动态转变。其机制与遗传、神经内分泌、自由基代谢和肠道菌群变化等生物学因素相关, 且小胶质细胞可能在其中起着重要的中介作用。诸多的生物学因素与年龄、性别和经济地位等人口学因素共同决定着心理社会应激的免疫反应发生发展。在其干预中, 运动疗法中的体育锻炼是极为值得重视的一种手段。