3: Eur J Cancer 1999 Oct;35(11):1603-7 Psychoneuroimmunology and cancer: fact or fiction? Kiecolt-Glaser JK, Glaser R. Department of Psychiatry, Ohio State University College of Medicine, Columbus 43210, USA. kiecolt-glaser.1@osu.edu There is substantial evidence from both healthy populations as well as individuals with cancer linking psychological stress with immune downregulation. This discussion highlights natural killer (NK) cells, because of the role that they may play in malignant disease. In addition, distress or depression is also associated with two important processes for carcinogenesis: poorer repair of damaged DNA, and alterations in apoptosis. Conversely, the possibility that psychological interventions may enhance immune function and survival among cancer patients clearly merits further exploration, as does the evidence suggesting that social support may be a key psychological mediator. These studies and others suggest that psychological or behavioural factors may influence the incidence or progression of cancer through psychosocial influences on immune function and other physiological pathways. Publication Types: Review Review, tutorial PMID: 10673969 [PubMed - indexed for MEDLINE]

4: Am J Med 1998 Sep 28;105(3A):35S-42S Stress-associated immune modulation: relevance to viral infections and chronic fatigue syndrome. Glaser R, Kiecolt-Glaser JK. Department of Medical Microbiology and Immunology, Comprehensive Cancer Center, The Ohio State University College of Medicine, Columbus 43210, USA. The frequent association of an active viral infection with the symptoms of CFS led researchers to hypothesize that chronic fatigue syndrome (CFS) is induced by a virus. Results of these studies indicated that despite clinical support for this hypothesis, there were no clear data linking viruses to CFS. In this overview, we will explore the interrelation of the immune, endocrine, and central nervous systems, and the possibility that stress and/or the reactivation/replication of a latent virus (such as Epstein Barr virus) could modulate the immune system to induce CFS. Relevant research conducted in the developing field of psychoneuroimmunology will be reviewed, with a particular focus on cytokine synthesis, natural killer (NK) cell activity, and T-lymphocyte function, as they relate to CFS. Publication Types: Review Review, tutorial PMID: 9790480 [PubMed - indexed for MEDLINE]

5: Ann N Y Acad Sci 1998 May 1;840:664-73 Autonomic, neuroendocrine, and immune responses to psychological stress: the reactivity hypothesis. Cacioppo JT, Berntson GG, Malarkey WB, Kiecolt-Glaser JK, Sheridan JF, Poehlmann KM, Burleson MH, Ernst JM, Hawkley LC, Glaser R. Department of Psychology, Ohio State University, Columbus 43210, USA. Cacioppo.1@osu.edu We examined the effects of brief psychological stressors on cardiovascular, neuroendocrine, and cellular immune response in 22 older women to investigate the common effects of stress across systems. Results revealed that psychological stressors heightened cardiac sympathetic activation, elevated plasma catecholamine concentrations, and affected the cellular immune response (ps < 0.05). In a replication and extension, 27 women caring for a spouse with a progressive dementia (high chronic stress) and 37 controls category matched for age and family income (low chronic stress) performed the 12-min laboratory stressor. Measures were taken before (low acute stress) and immediately following (high acute stress) exposure to the laboratory stressors as well as 30 min after termination of the stressor (recovery period). Acute stress again heightened cardiac sympathetic activation, elevated plasma catecholamine concentrations, and affected cellular immune responses (ps < 0.05), whereas chronic stress was associated with higher reports of negative affect, enhanced cardiac sympathetic activation, elevated blood pressure and plasma levels of ACTH, and diminished production of interleukin-1 beta (ps < 0.05). Correlational analyses in both studies further suggested that individuals who showed the greatest stress-related changes in HPA activation also exhibited the greatest diminution in cellular immune response. Publication Types: Review Review, tutorial PMID: 9629293 [PubMed - indexed for MEDLINE]

6: Lancet 1995 Nov 4;346(8984):1194-6 Comment in:  Lancet. 1996 Jan 6;347(8993):56 Slowing of wound healing by psychological stress. Kiecolt-Glaser JK, Marucha PT, Malarkey WB, Mercado AM, Glaser R. Department of Psychiatry, Ohio State University College of Medicine, Columbus, USA. There is evidence that psychological stress adversely affects the immune system. We have investigated the effects of such stress, caused by caring for a relative with Alzheimer's disease, on wound healing. We studied 13 women caring for demented relatives (mean age 62.3 [SE 2.3] years) and 13 controls matched for age (60.4 [2.8] years) and family income. All subjects underwent a 3.5 mm punch biopsy wound. Healing was assessed by photography of the wound and the response to hydrogen peroxide (healing was defined as no foaming). Wound healing took significantly longer in caregivers than in controls (48.7 [2.9] vs 39.3 [3.0] days, p < 0.05). Peripheral-blood leucocytes from caregivers produced significantly less interleukin-1 beta mRNA in response to lipopolysaccharide stimulation than did controls' cells. Stress-related defects in wound repair could have important clinical implications, for instance for recovery from surgery. PMID: 7475659 [PubMed - indexed for MEDLINE]

7: J Consult Clin Psychol 1992 Aug;60(4):569-75 Psychoneuroimmunology: can psychological interventions modulate immunity? Kiecolt-Glaser JK, Glaser R. Department of Psychiatry, Ohio State University College of Medicine, Columbus 43210. There is ample evidence from human and animal studies demonstrating the downward modulation of immune function concomitant with a variety of stressors. As a consequence, the possible enhancement of immune function by behavioral strategies has generated considerable interest. Researchers have used a number of diverse strategies to modulate immune function, including relaxation, hypnosis, exercise, classical conditioning, self-disclosure, exposure to a phobic stressor to enhance perceived coping self-efficacy, and cognitive-behavioral interventions, and these interventions have generally produced positive changes. Although it is not yet clear to what extent these positive immunological changes translate into any concrete improvements in relevant aspects of health, that is, alterations in the incidence, severity, or duration of infectious or malignant disease, the preliminary evidence is promising. Publication Types: Review Review, tutorial PMID: 1506504 [PubMed - indexed for

11: Psychol Rev 1999 Jul;106(3):529-50 A neuropsychological theory of positive affect and its influence on cognition. Ashby FG, Isen AM, Turken AU. Department of Psychology, University of California, Santa Barbara 93106, USA. ashby@psych.ucsb.edu Positive affect systematically influences performance on many cognitive tasks. A new neuropsychological theory is proposed that accounts for many of these effects by assuming that positive affect is associated with increased brain dopamine levels. The theory predicts or accounts for influences of positive affect on olfaction, the consolidation of long-term (i.e., episodic) memories, working memory, and creative problem solving. For example, the theory assumes that creative problem solving is improved, in part, because increased dopamine release in the anterior cingulate improves cognitive flexibility and facilitates the selection of cognitive perspective. Publication Types: Review Review, tutorial PMID: 10467897 [PubMed - indexed for MEDLINE]

12: J Pers Soc Psychol 1987 Jun;52(6):1122-31 Positive affect facilitates creative problem solving. Isen AM, Daubman KA, Nowicki GP. Four experiments indicated that positive affect, induced by means of seeing a few minutes of a comedy film or by means of receiving a small bag of candy, improved performance on two tasks that are generally regarded as requiring creative ingenuity: Duncker's (1945) candle task and M. T. Mednick, S. A. Mednick, and E. V. Mednick's (1964) Remote Associates Test. One condition in which negative affect was induced and two in which subjects engaged in physical exercise (intended to represent affectless arousal) failed to produce comparable improvements in creative performance. The influence of positive affect on creativity was discussed in terms of a broader theory of the impact of positive affect on cognitive organization. PMID: 3598858 [PubMed - indexed for MEDLINE]

13: Psychoneuroendocrinology 1999 Aug;24(6):613-27 Emotional stability, anxiety, and natural killer activity under examination stress. Borella P, Bargellini A, Rovesti S, Pinelli M, Vivoli R, Solfrini V, Vivoli G. Department of Hygiene, Microbiology, and Biostatistics, University of Modena and Reggio Emilia, Italy. This study was performed to evaluate the relation between a stable personality trait, a mood state and immune response to an examination stress. A self-reported measure of emotional stability (BFQ-ES scale) was obtained in a sample (n = 39) randomly selected from 277 cadets; this personality trait was also investigated by completing a neuroticism scale (Eysenck personality inventory) and a trait-anxiety scale (STAI). Natural killer (NK) cell activity was measured at baseline, long before the examination time and the examination day. The state-anxiety scale evaluated the response to the stressful stimulus. Taking subjects all together, the academic task did not result in significant modification over baseline in NK cell activity. Subjects were then divided into three groups based on emotional stability and state-anxiety scores: high emotional stability/low anxiety, medium, and low emotional stability/high anxiety. Examination stress induced significant increases in NK cell activity in the high emotional stability/low anxiety group, no effect in the medium group, and significant decreases in the low emotional stability/high anxiety group. The repeated-measure ANOVA revealed a significant interaction of group x period (baseline vs. examination) for both lytic units and percent cytolysis. The results did not change after introducing coffee and smoking habits as covariates. Our findings suggest that the state-anxiety acts in concert with a stable personality trait to modulate NK response in healthy subjects exposed to a psychological naturalistic stress. The relation between anxiety and poor immune control has been already described, whereas the ability of emotional stability to associate with an immunoenhancement has not yet reported. The peculiarity of our population, a very homogeneous and healthy group for life style and habits, can have highlighted the role of emotional stability, and may account for the difference with other studies. PMID: 10399771 [PubMed - indexed for MEDLINE]

14: Brain Behav Immun 1999 Jun;13(2):155-74 Differential immune system changes with acute and persistent stress for optimists vs pessimists. Cohen F, Kearney KA, Zegans LS, Kemeny ME, Neuhaus JM, Stites DP. Department of Psychiatry, University of California, San Francisco, USA. This study investigated whether acute and persistent stressors and life change events were followed by changes in immune status, and whether dispositional optimism moderated these relationships. Thirty-nine healthy women ages 18-45 were followed prospectively for 3 months, with weekly assessment of acute and persistent stressors and monthly assessment of life events and immune parameters (NK cell cytotoxicity, and CD4 and CD8 T cell subsets). The study used an autoregressive linear model to examine how weekly appraised acute and persistent stress levels were associated with immune parameters in the subsequent week. Analyses revealed that the immune outcomes were differentially affected by acute and persistent stressors. Further, the association between acute stress and subsequent immune parameters was buffered by an optimistic perspective. However, when stress persisted at high levels, optimists showed more subsequent immune decrements than pessimists. Copyright 1999 Academic Press. Publication Types: Clinical trial PMID: 10373279 [PubMed - indexed for MEDLINE]

15: Psychosom Med 1997 Jul-Aug;59(4):447-57 Chronic life stress alters sympathetic, neuroendocrine, and immune responsivity to an acute psychological stressor in humans. Pike JL, Smith TL, Hauger RL, Nicassio PM, Patterson TL, McClintick J, Costlow C, Irwin MR. Department of Psychiatry-9116-A, Veteran's Affairs Medical Center, San Diego, CA 92161, USA. OBJECTIVE: Life stress is hypothesized to alter the dynamic regulation of the autonomic, neuroendocrine, and immune systems. This study examined the effects of antecedent chronic life stress on psychological and physiological responsivity after acute challenge with a psychological stressor. METHOD: Using a within-subject mixed design, male volunteers with (N = 12) and without chronic life stress (N = 11) were administered a 12-minute laboratory stressor (mental arithmetic) vs a video control. RESULTS: Acute psychological stress induced subjective distress, increases of circulating concentrations of epinephrine, norepinephrine, beta-endorphin, adrenocorticotropic hormone (ACTH), and cortisol, and a selective redistribution of natural killer (NK) cells into the peripheral blood as compared with the video control condition. Although the two groups were almost identical at baseline in psychological, sympathetic, neuroendocrine, and immune domains, the chronic stress group showed greater subjective distress, higher peak levels of epinephrine, lower peak levels of beta-endorphin and of NK cell lysis, and a more pronounced redistribution of NK cells in response to the acute psychological challenge than the controls. Furthermore, the acute stressor induced a protracted decline in NK lysis per NK cell in the chronic stress group but had no effect in the controls. CONCLUSIONS: In summary, when persons who are undergoing chronic life stress are confronted with an acute psychological challenge, an exaggerated psychologic and peak sympathomedullary reactivity occurs that is associated with decrements in individual NK cell function and is protracted beyond termination of the stressor and sympathomedullary recovery. PMID: 9251165 [PubMed - indexed for MEDLINE]

16: Brain Behav Immun 1992 Jun;6(2):141-56 Modulation of human natural killer cell activity by exposure to uncontrollable stress. Sieber WJ, Rodin J, Larson L, Ortega S, Cummings N, Levy S, Whiteside T, Herberman R. Department of Psychology, Yale University, New Haven, Connecticut 06520-7447. Changes in natural killer cell (NK) activity and proportions of circulating T and NK lymphocyte subsets were assessed in adult males immediately after exposure to controllable or uncontrollable stress (noise) as well as 24 and 72 h later, in order to track the time course of the effects of stress. The role of control-relevant personality variables as moderators of the stress-immunosuppression relationship was considered. Subjects who perceived they had control over the noise as well as no-noise "control" subjects showed no reduction in NK activity. By contrast, subjects who perceived that they had no control over the stressor showed reduced NK activity immediately after the conclusion of the first 20-min stress session, and the reduced NK activity was found as long as 72 h later. Optimism and one's desire to be in control enhanced the negative impact of uncontrollable noise on NK activity. No differences between conditions were found on number of NK cells or a variety of T cell subsets. The results suggest the importance of perceived control in moderating the short- and long-term effects of stress on NK activity. PMID: 1504368 [PubMed - indexed for MEDLINE]

17: Biol Psychiatry 1990 Jan 1;27(1):22-30 Reduction of immune function in life stress and depression. Irwin M, Patterson T, Smith TL, Caldwell C, Brown SA, Gillin JC, Grant I. Veterans Administration Medical Center, Clinical Research Center on Alcoholism, San Diego, CA 92161. Reduced cell-mediated immune function has been found in depressed patients and in distressed persons undergoing threatening life events. The present study examines the interaction between severe life stress and major depression to produce immune alterations in 36 matched pairs of hospitalized depressed patients and nondepressed controls. Both major depressive disorder and the presence of threatening life events in control subjects are independently associated with a 50% reduction of natural killer (NK) cytotoxicity. A decrease in natural cytotoxicity is significantly associated with depressive symptoms but not with age, alcohol consumption, or tobacco smoking. These findings of altered immunity provide further evidence that the physiological responses in chronic stress parallel those found in the syndrome of depression. PMID: 2297549 [PubMed - indexed for MEDLINE]