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International Updates

Psychoneuroimmunology

Issue 80

Issue 79

KIECOLT-GLASER and colleagues, Department of Psychiatry, The Ohio State University College of Medicine, 1670 Upham Drive, Columbus, Ohio 43210, USA, Kiecolt-Glaser.1@osu.edu, reviewed (176 references) literature providing evidence that links negative emotions with the onset and course of a range of illnesses/conditions that can be influenced by the immune system.
Background: Inflammation has been associated with a wide range of age-related conditions such as cardiovascular disease, osteoporosis, arthritis, type 2 diabetes, certain cancers, Alzheimer’s disease, frailty and functional decline and periodontal disease. Negative emotions and stress can directly stimulate production of proinflammatory cytokines, which influence these and other conditions. Negative emotions can also help prolong infection and delay wound healing, resulting in sustained production of proinflammatory mediators.
Discussion: The authors of this review argue that negative emotions and distress may contribute to dysregulation of normal immune function, and that this may be one core mechanism precipitating the appearance of and/or fuelling the progression of a range of common diseases and conditions of diminished health. Factors that reduce negative emotions, such as close personal relationships, may therefore enhance health partly through their beneficial effects on immune and hormonal functions.
Kiecolt-Glaser JK et al. Emotions, morbidity, and mortality: new perspectives from psychoneuroimmunology. Annual Review of Psychology 53: 83-107. 2002.

Comment: Readers are also referred to Kiecolt-Glaser’s review of the literature regarding psychoneuroimmunology in Issue 78 of Positive Health (see below).

Issue 78

KIECOLT-GLASER and colleagues, Department of Psychiatry, Ohio State University, Columbus, Ohio 43210, USA, kiecolt-glaser.1@osu.edu, reviewed (155 references) early and recent research relevant to the field of psychoneuroimmunology (PNI).
Background: Brain-immune modulation is now a well-established phenomenon, with an explosion of research and literature on the subject appearing over the last decade. The history of the field goes back much farther, however, largely under the auspices of studies in psychosomatic medicine. This article reviews that history and speculates on where PNI may take us in the future.
Methods: Human PNI studies published since 1939, particularly in the journal Psychosomatic Medicine, are reviewed here. Studies were grouped according to key themes, such as: stressor duration and characteristics (e.g. laboratory stressors, short-term stressors, chronic stress); influences of psychopathology, personality or interpersonal relationships; and immune responses to behavioural interventions. The authors also examined population trends, changes and developments in immunological assessment methods, health outcomes and likely future directions in the field of PNI.
Results: The body of evidence is now sufficient to conclude that psychosocial stressors or interventions can cause alterations in immune function that can result in actual changes in health. The strongest evidence of this is in the areas of infectious diseases and wound healing. In addition, it is now apparent that the onset and course of a range of common diseases are significantly influenced by proinflammatory cytokines; such conditions range from cardiovascular disease to loss of function and frailty such as those commonly associated with ageing. Numerous studies have demonstrated that negative emotions (e.g. anger, depression, despair) and stressful experiences can directly stimulate production of proinflammatory cytokines; chronic or recurrent infections are also indirect stimulators of these agents. Thus, the wide range of health risks associated with negative emotions may be mediated, in large part, by distress-related disturbances of normal immune function.
Conclusion:The facts of PNI have far-reaching implications for basic biological sciences, academic and clinical medicine and the effectiveness of healthcare.
Kiecolt-Glaser JK et al. Psychoneuroimmunology and psychosomatic medicine: back to the future. Psychosomatic Medicine 64 (1): 15-28. Jan-Feb 2002.
Comment:Kiecolt-Glaser are amongst the giants in the field of psychoneuroimmunology. This review summarizes the vast research which substantiates how the mind has a powerful influence upon health, as also discussed in the featured cover stories. The importance of psychosocial and emotional factors to disease and general health must now finally be given the emphasis they merit, starting with the medical school curriculum and finishing up in medical consultations placing the overall wellbeing of the patient as the supreme consideration.

Issue 21

ROGERS and FOZDAR, Department of Psychiatry, Harvard Medical School, Boston Massachussetts, USA write that the interactions between the immune system and psychological states are intricate and intriguing and that research at the mulecular level has shed light on the previously poorly-defined area of psychoneuroimmunology (PNI). The authors review (73 references) the PNI of autoimmune disorders, most particularly rheumatoid arthritis and lupus erythematosus. Research using animal models have been useful in revealing some of the complex PNI interactions. The effect of stress upon the onset and course of autoimmune disorders has also added to our understanding of psychoneuroimmunological interactions, which are bi-directional, as reflected in the autoimmune-mediated neuropsychiatric symptoms of systemic lupus. The authors state that exploring the role of various neurotransmitters and neuromodulators involved in the stress response may have important therapeutic implications for autoimmune disorders.
Rogers MP and Fozdar M. Psychoneuroimmunology of autoimmune disorders. Adv Neuroimmunol 6(2): 169-77. 1996.

COYLE, Department of Neurology, Health Sciences Center, State University at New York (SUNY), Stony Brook USA writes that the aim of this clinical review (83 references) is to highlight recent advances in immunology and information from selected other fields which have resulted in a better appreciation of neuroimmunological mechanisms involved in Multiple sclerosis (MS). New research information regarding immunopathology, the cytokine network and the role of oligodendrocytes, lymphocytes and endothelial cells in MS have resulted in new therapeutic approaches. Additionally, new information regarding clinical course and neuroimaging disease features and the role of genetic factors and infectious agents have improved the understanding of the immune basis for MS.
Coyle PK. The neuroimmunology of multiple sclerosis. Adv Neuroimmunol. 6(2): 143-54. 1996.

FRICCHIONE and colleagues, Brigham and Women’s Hospital, Division of Psychiatry, Boston, Massachussetts USA review (60 references) the role of the macrophage in the pathology of coronary artery disease (CAD), in which the central interaction of macrophage, endothelial and smooth muscle cell is considered in the context of hyperlipidaemia. The macrophage appears to be at the start of a chain of events starting with elevated low density lipoprotein (LDL). Stress, especially in those people with a core hostility, may be associated with higher catecholamine levels as well as higher serum lipid levels which will be processed by macrophage and endothelial cells to oxidised LDL. Oxidised LDL molecules will contribute to atherosclerotic plaque, a side effect of which may be a diminished vasodilatory response to the nitric oxide (NO) produced by macrophages and endothelium. In fact, paradoxical vasoconstriction occurs in atherosclerosis in response to neurotransmitters including serotonin and acetylcholine which under normal conditions produce vasodilation. There is also evidence that macrophages and endothelial cells can both regulate NO production via a specific mu-3 morphine receptor, which can be blocked by naloxone, which may explain the clinical effectiveness of morphine and nitroglycerin in patients with CAD. The authors state that more research is needed to elucidate the neuroimmunologic basis for atherosclerosis which could lead to prospects for better treatment and management in the future.
Fricchione GL et al. Neuroimmunologic implications in coronary artery disease. Adv Neuroimmunol 6(2): 131-42. 1996.

ANDERSON, Department of Psychiatry, Harvard Medical School, Boston Massachusetts, USA reviews (61 references) the research literature regarding the links between human immune function and mood disorders. The initial steps of this fledgling research area since its inception during the late 1970s are summarised, and a range of studies needed to enhance our neuroimmunological understanding are outlined. The author writes that future investigations will require more specificity in several realms of inquiry: diagnostic, epidemiologic and physiologic. Basic physiological studies required in both neurophysiology and immunology in order to provide a basis for meaningful examination of their interface are highlighted. One area which requires more specific investigation both in immunologic and mood disorders research is that of temporal organisation. And just as psychiatric researchers have started to scrutinise temporal cycles of mood, behaviour and neurophysiology, so also should exploration of immune functioning take into account predictable temporal cycles including circadian and ultradian rhythms, as they shape responses to unanticipated external disturbances. Clarification of the temporal dimension will significantly add to the analysis of the links between immune functioning and mood disorders. New discoveries revealing hitherto unknown mechanisms are made as the basic science of psychoneuroimmunology continues to mature. However this field is still on the frontier and explanations of the long suspected links between mood disorders and immune functioning are still awaited.
Anderson JL. The immune system and major depression. Adv Neuroimmunol 6(2): 119-29. 1996.

CHRISTENSEN and colleagues, Department of Psychology, Unviersity of Iowa, Iowa City USA examined the immunological effects of self-disclosing personal information about a traumatic or stressful experience and examined the hypothesis that the effect of self-disclosure upon immune function is moderated by individual differences in cynical hostility.
METHODS: 43 male college undergraduates who were classified as high or low on the Cook-Medley Hostility scale were randomly assigned to either a verbal self-disclosure or a nondisclosure discussion procedure. Task-induced changes in natural killer (NK) cell activity (ie cytotoxicity) was the dependent variable.
RESULTS: There was a significant interaction between the discussion procedure and hostility. In the self-disclosure group, the high hostility subjects showed a significantly greater increase in NK cell cytotoxicity compared to the men with low hostility scores.
CONCLUSIONS: The effect of self-disclosure upon NK cell activity is moderated by an individual’s level of cynical hostility. The greater short term enhancement in NK cell activity seen in hostile people is likely to be correlated with a more pronounced acute arousal response elicited by the self-disclosure task.
Christensen AJ et al. Effect of verbal self-disclosure on natural killer cell activity: moderating influence of cynical hostility. Psychosom Med 58(2): 150-5. Mar-Apr 1996.

MILLS and DIMSDALE, Department of Psychiatry, University of California, San Diego, La Jolla USA conducted a pilot study to examine the effects of a 6-minute speaking stressor upon several cellular adhesion molecules, which are cell-surface receptors responsible for mediating interactions among leukocytes, platelets and vascular endothelium.
METHODS: 22 healthy men and women were included in the study, which looked at several CAMs, including L-selectin, ICAM-1 and the integrins.
RESULTS: The psychologic stressor caused a significant decrease in L-selectin. During stress women increased whereas men decreased in 3 markers of the integrin family, LFA-1, LFA-2 and LFA-3. There was no significant task effect upon ICAM-1 nor group differences in state anger or anxiety ratings. Changes in LFA-1 and LFA-2 were negatively correlated with age, indicating that older subjects showed less change in these markers than younger subjects.
CONCLUSIONS: These preliminary results suggest that the immune activation which acompanies acute psychological stress may be sufficient to change the expression of certain cellular adhesion molecules. Further research should be directed towards determining whether cellular adhesion molecule expression is changed equally across various leukocyte subsets or is restricted to specific cell types.
Mills PJ and Dimsdale JE. The effects of acute psychologic stress on cellular adhesion molecules. J Psychosom Res 441(1): 49-53. Jul 1996.

COMMENTS: The sophistication of the above research studies shows the depth and breadth of psychoneuroimmunology, even as it relates to serious diseases such as rheumatoid arthritis, multiple sclerosis, and lupus.