Psychoneuroimmunology: The Experiential Dimension.

Accumulating evidence has made clear that experience-the knowledge an individual acquires during a lifetime of sensing and acting-is of fundamental biological relevance. Experience makes an impact on all adaptive systems, including the endocrine, immune, and nerve systems, and is of the essence, not only for the unfolding of an organisms' healthy status, but also for the development of malfunctional traits. Nevertheless, experience is often excluded from empirical approaches. A variety of complex interactions that influence life histories are thereby neglected. Such ignorance is especially detrimental for psychoneuroimmunology, the science that seeks to understand how the exquisite and dynamic interplay between mind, body, and environment relates to behavioral characteristics. This chapter reviews claims for incorporating experience as a member of good explanatory standing in biology and medicine, and more specifically claims that experiential knowledge is required to enable meaningful and relevant explanations and predictions in the psychoneuroimmunological realm.

Ecological Context and Human Variation: Applying the Principles of Biological Anthropology to Psychoneuroimmunology.

There is considerable research interest overlap between biological anthropology and psychoneuroimmunology (PNI), particularly given recent anthropological interest in endocrine and immune system functioning over the life span and in different environmental contexts. In this chapter, I argue that conducting research on non-WEIRD populations and applying an anthropological, evolutionary approach to PNI can greatly strengthen our understanding of immune-endocrine-behavior connections. This chapter reviews population-level variation in the human immune and endocrine systems, as well as genetic and environmental contributions to this variation. The effects of culture on shaping health outcomes and stress responses are also considered. Finally, this chapter discusses some noninvasive sampling methodologies appropriate to field research and alternatives to laboratory-based research designs. By confronting variable social and environmental contexts, PNI can greatly expand on its existing contributions to the treatment and understanding of depression, mood disorders, stress, and other aspects of health and well-being.

[Cytokines in psychoneuroendocrine immunological context of nonspecific musculoskeletal pain]. / Zytokine im psychoneuroendokrin-immunologischen Kontext unspezifischer muskuloskeletaler Schmerzen.

Cytokines are coordinators of immune homeostasis. Evidence for the participation of cytokines in neurogenic inflammation, peripheral and central sensitization and hyperalgesia as well as for induction of inflammatory immune responses by pain-related catastrophizing is well documented. A disproportion of proinflammatory and anti-inflammatory cytokines is known to be a contributory cause of pain and pain behavior. Embedded into psychoneuroendocrine immunological feedback control systems cytokines are able to perpetuate a virtuous circle between local inflammation and systemic pain behavior (pain/sickness behavior) thus contributing to chronification of nonspecific musculoskeletal pain.In this model avoidance and pain-related nonrecognition as key components of systemic pain behavior lead to maintenance of the virtuous circle by generating of a local inflammation with local and systemic consequences. This model can explain the success of established therapy concepts from the point of view of psychoneuroimmunology, such as fear avoidance, which are effectively used as principal components in multimodal pain therapy.

[Psychoneuroimmunology: an update]. / Psychoneuroimmunologie: Ein Update.

Psychoneuroimmunology (PNI) is closely associated with the bidirectional pathways between mind/brain and the immune system. PNI research represents a rapidly growing area within psychosomatic research. Recent studies in PNI are based mainly on the immunological concepts of Th1/Th2 dichotomy and inflammation. This review covers human PNI studies dealing with stress-associated changes in cytokine (Th1, Th2) levels in immune-related processes such as wound healing, atopic diseases as well as autoimmune and other inflammatory diseases. It is shown that PNI studies measuring immune activity near the site of the disease (e. g. woundhealing) and dealing with objective stressors show more consistent findings (stress-associated Th1/Th2 shift, stress-associated proinflammatory activation) than those dealing with chronic and complex diseases (e. g., autoimmune disease). This warrants the expansion of the methodological repertoire in future PNI research toward designs allowing for the investigation of complex psychosomatic phenomena.

The mind-body connection: not just a theory anymore.

The field of psychoneuroimmunology has witnessed an explosion of empirical findings during the last two decades. Research has documented the mechanisms through which stressful emotions alter white blood cell function. Stress diminishes white blood cell response to viral infected cells and to cancer cells. Moreover, vaccination is less effective in those who are stressed and wounds heal less readily in those who are stressed. While stress decreases the activity of some white blood cells, stress does not compromise the function of all types of white blood cells. Indeed, some types of autoimmune disease, which involve particular subsets of white blood cells, are exacerbated by stress. The literature documents the efficacy of talk-therapy interventions in altering immune system parameters and enhancing the body's ability to combat disease. The literature also documents the impact of the chronic stress of poverty on immune system function.

From psychosomatic to psychological medicine: what's the future?

PURPOSE OF REVIEW: Recent research findings into putative psychobiological mechanisms of emotional disorders as the future development of psychosomatic medicine are discussed. RECENT FINDINGS: Recent studies reinforce the communication between the immune and central nervous systems and identify the large set of peptide and nonpeptide neurotransmitters and ligands they share. Cytokines are seen as humoral mediators that may explain the interaction between endocrine and immune systems. The hypothalamic-pituitary axis has been investigated as part of the regulatory circuits that interact with autonomic regulation to expose immunologic processes related to stress or depression, and also to several diseases. Immune dysregulation and psychological distress have been linked to each other in disease, chronic stress, bereavement and other major life events. Research findings in depressive disorders and cancer may generate new theoretical paradigms in psychosomatic medicine. SUMMARY: The clinical understanding and management of distress or emotional disorders associated with physical illness may change in future because of the results of interdisciplinary research, where environmental factors will be integrated with psychological and biological systems, mainly of endocrine or neuroimmunological nature. The ultimate goal of psychosomatic medicine may be the integration of different levels of individual functioning on a systemic basis.

Stress effects on lung function in asthma are mediated by changes in airway inflammation.

OBJECTIVE: To examine the association of changes in current negative mood and long-term daily hassles with changes in lung function and airway inflammation in patients suffering from asthma and in healthy controls. Associations between psychological factors and asthma symptoms have been documented, but the relationship between airway inflammation and psychological factors has been largely unexplored. METHOD: Data were analyzed from 46 asthma patients and 25 controls who completed questionnaires on current mood and daily hassles at two assessments 3 months apart. Lung function was measured by spirometry (forced expiratory volume in the first second (FEV(1))) and airway inflammation by the fraction of nitric oxide in exhaled air (FeNO). Regression analyses controlling for allergen load and air pollution (ozone) were calculated to study the association between changes in psychological factors and changes in lung function and airway inflammation, and to examine the mediational role of airway inflammation in the stress-lung function association. RESULTS: In patients with asthma, increases in negative affect were associated with decreases in FEV(1) and increases in FeNO. For daily hassles, a reverse pattern of associations was found, with decreases in daily hassles linked to decreases in FEV(1) and increases in FeNO. Mediation analyses showed that FeNO was a significant mediator of the association of both negative affect and daily hassles with lung function changes. No significant associations were found for healthy controls. CONCLUSION: Psychological variables are consistently associated with spirometric lung function and airway inflammation in asthma patients. For asthma patients, effects of acute negative affect must be distinguished from more chronic distress due to daily hassles.

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.

Neuroimmunologic influences in neuropsychiatric and psychophysiologic disorders.

Top down central nervous system (CNS) influences on the immune system and bottom up immune system influences on the CNS take part in a complex feedforward and feedback loop which may be responsible for initiating events and perpetuating circumstances in the course of neuropsychiatric as well as immune system diseases. In this paper the authors examine the neuroendocrine-neuroimmune stress response system, the concept of autoimmunoregulation, and recent studies of immune and pharmacological dysregulation in neuropsychiatric and psychosomatic illnesses. The authors review the recent English language literature on these subjects. Support for the hypothesis that macrophages play an important role in neurodevelopment and in the pathophysiology of various neuropsychiatric conditions is found. The interplay between neurologic and immune systems may help to uncover the pathophysiologies of certain neuropsychiatric systems. This may provide new strategies for pharmacologic anti inflammatory treatments. The monocyte /macrophage, which crosses the blood brain barrier is an essential candidate cell in the study of psychoneuroimmunology.

[The competent cell - the immune system as a metaphor, sign, language and culture]. / Die kompetente Zelle - das Immunsystem als Metapher, Zeichen, Sprache und Kultur.

We investigated how the progressive function of the metaphor, the model world of signs, language and culture, link the cell's immunological knowledge with a perceivable concept of the body. Using ethnomethodologically oriented, partly interpretative text analysis, we examined the lymphocyte stimulation test, word clusters in immunology and other medical specialties, the linguistic presentation of the body in German, American and the internet, the presentation of the "self" of the cell in biology and immunology, and protocols of oncological out-patient interviews and chatrooms. When an abstract sign model is created, then the existence of a "negotiable", "competent" and "tolerant" immune cell is predominated by the concept of a cell and much less by elements of the body. Thus, the passive, spatial-anatomical concept of the body can be overcome and the position of the microscopically describable inner observer achieved. This is related to the American concept of a body that can be formed at will from animated individual parts. This model immune system impresses upon physical life and also provides a new metaphor for human interaction in accordance with the pattern of immunocompetent cells.

[The psychosomatic correlations and the antibodies to lung tissue in patients with bronchial asthma]. / Psykhosomatychni zv'iazky ta antytila do lehenevoï tkanyny u khvorykh na bronkhial'nu astmu.

Forty-four patients with bronchial asthma, aside from clinical and functional evaluation, were studied for the psychological profile (MMPI-test) and the presence of antibodies to the lung tissue. The correlations established were as follows: normal titers of antibodies to the lung tissue--more agreeable and satisfactory psychological profile of the patients, the lower or higher the antibody titer, the less acceptable is the psychological profile.

Epstein-Barr virus antibodies in whole blood spots: a minimally invasive method for assessing an aspect of cell-mediated immunity.

OBJECTIVE: Study 1: Introduce and validate a method for measuring EBV p18-VCA antibodies in whole blood spots to provide a minimally invasive marker of cell-mediated immune function. Study 2: Apply this method to a large community-based study of psychopathology in children and adolescents. METHODS: The EBV antibody method was evaluated through analysis of precision, reliability, stability, and comparisons with plasma and indirect immunofluorescence methods. The effects of life events on p18-VCA antibody level were considered in a subsample of 9, 11, and 13 year-old children participating in the Great Smoky Mountains Study in North Carolina. The subsample was stratified by age, sex, and degree of overall life strain. RESULTS: Dried blood spots provided a convenient, sensitive, precise, and reliable method for measuring EBV p18-VCA antibody titer. Life events were positively associated with p18-VCA antibodies in girls but not in boys. CONCLUSIONS: The validity of the blood spot EBV p18-VCA antibody assay, as well as the ease of sample collection, storage, and transportation, may provide an opportunity for psychoneuroimmunology to explore a wider range of stress models in larger, community-based studies.

Dynamics of stress-related decrease of salivary immunoglobulin A (sIgA): relationship to symptoms of the common cold and studying behavior.

The dynamics of stress-related decrease of salivary Immunoglobulin A (sIgA) were examined with respect to whether an increase of upper respiratory tract (URT) symptoms can be observed concurrently with or subsequent to sIgA alterations and whether one can use students' studying behavior during academic examinations to predict changes in sIgA. From a 2-part medical examination of 42 students, daily measures of sIgA were obtained, and symptoms of URT infections and studying behavior were determined by means of questionnaires. Assessment periods began 7 days before each part of the academic examination began and lasted until the 6th day afterward. A control group of 24 medical students who were not undergoing examinations also responded to all questionnaires. A progressive suppression of sIgA, outlasting the examination period by more than 6 days, was observed. Time spent studying explained a significant proportion in sIgA variation. However, no relationship between sIgA and URT symptoms was observed, nor did students who took academic examinations differ from untested controls in symptom rates.

Implicações psiconeuroimunológicas do estresse no desencadeamento de doenças / Psychoneuroimmunology of stress implications in unchain diseases

Os autores apresentam as correlações do estresse com a patogênese de várias doenças. Antes, expõem os aspectos fundamentais da Psiconeuroimunologia, para uma compreensão das interconexões no complexo microambiente onde ocorrem as influências do estresse. Concluem que, apesar de todas as implicações do estresse na desestruturação da homeostasia imunológica ainda não estarem completamente definidas, e das limitações metodológicas, há consenso de que fatores estressantes propiciam a vulnerabilidade do organismo a determinadas doenças.

The authors introduce the correlations between stress and the pathogenesis of various diseases. Previously, they expose the fundamental factors of Psychoneuroimmunology for the comprehension of the inter-connections in the complex microenvoironment where the influence of stress occurs. They conclude that despite all the implications of stress on the desestruturation of immunologic homeostasy are not already completely defined and despite metodologic limitations, there are a consensus that stressor factors provide vulnerability to the organism concerned to certain disorders.

A dual pathway model of daily stressor effects on rheumatoid arthritis.

This study evaluated the initial promise of a dual-pathway conceptual model linking daily event stressors to rheumatoid arthritis (RA) disease activity through changes in immune system activation and mood. Fifty individuals, who were studied on five occasions two weeks apart, reported daily event stressors on the Daily Life Experience Checklist, daily mood on an abbreviated version of the Profile of Mood States-B, and daily joint pain on the Rapid Assessment of Disease Activity in Rheumatology. Serial clinical examinations comprised ratings of joint tenderness and swelling, and blood drawn during exams was analyzed for sedimentation rate (an indicator of systemic inflammation) and soluble interleukin-2 receptors (a marker of immune system activation known to correlate with RA disease activity). Across-person analyses failed to establish links from daily event stressors to either disease activity or composites of joint pain and joint inflammation when associations were adjusted for the effect of neuroticism on self-report measures. Pooled within-person analyses, however, were generally consistent with the relations predicted by the dual-pathway model. Increases in daily event stressors during the week preceding each clinical exam were associated with increased joint pain (regardless of changes in mood). At the same time, increased daily stressors were indirectly associated with decreased joint inflammation through reduction in levels of soluble interleukin-2 receptors. The dual-pathway model, which may be limited to short-term psychological and psychoimmunologic processes, underscores the importance of distinguishing potentially opposing effects of stress on pain versus inflammation in individuals with rheumatoid arthritis.

Shaking up immunity: psychological and immunologic changes after a natural disaster.

OBJECTIVE: The 1994 Northridge earthquake created life disruption and psychological distress for employees of the nearby Sepulveda VA Medical Center. We were interested in the immunologic correlates of disruption and distress under these stressful circumstances. METHOD: Sixty-eight employees were examined beginning 11 days post-earthquake and were observed until about 4 months after the earthquake, during which time three psychological and immunologic assessments were done. Subjects experienced life disruption from the earthquake itself, damage to home and possessions, injury to self and others, and damage to and functional disruption of workplace. Questionnaires assessed degree of life disruption (personal and work-related), mood, earthquake-specific distress, and repression (alexithymia, coping style or "Type C", and "immunosuppression-prone" traits). Immune measures included lymphocyte subsets-total T (CD3+), helper T (CD4+), cytotoxic T (CD3 + CD8+), B (CD19+), and natural killer (NK; CD3 - CD16 + CD56+)-as well as lymphoid cell mitogenesis (PHA and PWM), and NK cell cytotoxicity. RESULTS: Along with a lessening degree of distress over time, a number of immunologic measures declined over the assessment period (CD3+, CD8+, CD16 + 56+ cells. T cell blastogenesis, and NK cell cytotoxicity). Furthermore, subjects reporting low distress had higher numbers of CD3+ and CD8+ cells and a higher proliferative response to PHA. Those with distress corresponding to life disruption had highest levels of CD3+ and CD8+ cells. Measures of repression did not relate directly to immunity. CONCLUSION: These results suggest that appropriateness of psychological reaction to the realistic degree of life stress was least disruptive of an aspect of immunity.

[Insecure attachment and psychosomatic skin disease]. / Attaccamento insicuro e patologia psicosomatica della cute.

Alexithymia is not infrequent among psychosomatic patients. The incapacity to decode one's own emotional experience implies an exacerbation of the physiological response through a recursive loop. If this vicious circle is maintained it can increase the risk of psychosomatic diseases which could be in this way regarded as functions of external meaningful events mediated by the central nervous system. The meaning varies from one individual to another and depends on his cognitive-emotional organisation. In order to study such an organisation, it can be useful to classify his mental state regarding his attachment. The authors, who previously observed an association between psychosomatic skin disease and the "non-free" mental state with regard to attachment, suggest that further studies on psychosomatic patients should be conducted applying the principles and methods of the attachment theory.

Psychological stress, neuroimmunomodulation, and susceptibility to infectious diseases in animals and man: a review.

This article reviews research on the role of psychological stress, personality, social support and other psychosocial factors in bacterial, viral and parasitic infections. After 100 years of research on man and animals, psychological stress is considered as a potential cofactor in the pathogenesis of infectious disease. Psychological stress seems able to alter the susceptibility of animals and man to infectious agents, influencing the onset, course and outcome of certain infectious pathologies. Many experiments have identified in neuroimmunomodulation the principal mediator of the alterations associated with conditions of stress. The development of psychoneuroimmunology has fostered in-depth study of the complex relationship between psychosocial factors, the central nervous system, the immune system and infectious disease. Although antimicrobial drugs have certainly remained the basis of all anti-infective therapy, this type of study has already led some authors to propose and experiment protocols of psychological intervention or psychoimmunotherapy in pathologies such as tuberculosis, or herpes simplex virus or human immunodeficiency virus infections. The psychoneuroimmunological approach to infectious diseases will probably grow in importance in the future not only in the setting of research in psychosomatic medicine but also in that of clinical microbiology.

Immunity and stress.

The relationship between stress and immunity is not a hot topic of psychoneuroimmunology. The review outlines the main aspects of these interrelations; stress sensitive immunological markers, experimental research and studies on humans which underline the prevailing immunosuppressive effects of stress are discussed. A classification of stress-related diseases comprises autoimmune, acute, psychosomatic and neuroendocrine diseases. Besides the hypothalamopituitary-adrenocortical axis and the symparthoadrenal system, newer information points to the role of cytokines, opioids and other mediators in the complex mechanisms involved. Several data from the physiological laboratory in Cluj are included. The final consideration outlines some unclarified aspects and new research directions.