2002 - Rheumatology Interest Group Hosts: Joan E. Broderick, PhD, Department of Psychiatry, SUNY - Stony Brook, Stony Brook, NY & Alex J. Zautra, PhD, Department of Psychology, Arizona State University, Tempe, AZ A round-table discussion will provide attendees the opportunity to network and outline an agenda for rheumatology interests at future APS meetings. We will discuss what aspects of rheumatology research are most appropriate for this society. Ideas will be discussed for organizing symposium, poster sessions, and workshops for the 2003 meeting. A particular emphasis will be placed on establishing international connections and collaborations. 2001 - Rheumatologic and Musculoskeletal Disorders Hosts: Deborah N. Ader, PhD and Alex J. Zautra, PhD This roundtable will provide a forum for discussion and networking among researchers interested in rheumatologic and musculoskeletal disorders. We would like to bring together researchers interested in discussing their ongoing research and potential future directions for behavioral research in these disorders, and assess interest in increasing the visibility of this research at APS meetings. The National Institute of Arthritis, Musculoskeletal, and Skin Diseases (NIAMS) at NIH has an increased interest in and commitment to behavioral research; Dr. Ader will discuss this new emphasis and solicit feedback from participants. Dr. Zautra will assist in leading a discussion of key paradigms for psychosomatic research on clinical populations with musculoskeletal disorders 2002 - Gastrointestinal Disorders Interest Group Host: Susan B. Levenstein, MD, Rome, Italy This year will be the fifth luncheon meeting of the APS Gastroenterology Special Interest Group, bringing together researchers and clinicians interested in mind-body interactions in gastrointestinal disorders. Participants are invited to come talk about their own past and future activities and to network with other clinicians and researchers; several collaborative projects have grown out of these meetings in the past. 2001 - Gastrointestinal Disorders Hosts: Susan Levenstein, MD and Douglas Drossman, MD This year will be the fourth luncheon meeting of the APS Gastroenterology Special Interest Group, bringing together researchers and clinicians interested in mind-body interactions in gastrointestinal disorders. Participants are invited to come talk about their own past and future activities and to network with other clinicians and researchers; several collaborative projects have grown out of these meetings in the past. The group is also forwarding the APS special project of producing annotated slide sets for teaching the iopsychosocial model to students of medicine and psychology. Slide sets related to peptic ulcer and to inflammatory bowel disease are nearly final, and one for irritable bowel syndrome is under construction. 2000 - Gastrointestinal Disorders Hosts: Susan Levenstein and Douglas Drossman The third annual APS Gastroenterology Special Interest Group luncheon will again bring together researchers and clinicians interested in mind-body interactions in gastrointestinal disorders. The past year has been a particularly strong one for the biopsychosocial model as applied to organic GI disease, since new studies have debunked the exclusive causal role of H. pylori in peptic ulcer, and others have convincingly linked stress with exacerbations of inflammatory colitis. Research in functional GI disorders has been making great strides as well, especially with publication of the Rome criteria. All interested conference participants are invited to attend the luncheon in order to discuss these and other new developments, to share (or even seek collaborators for) their own recent, ongoing, and future research, and to discuss our possible role in a new APS project: producing curricular materials for teaching the biopsychosocial model to students of medicine and psychology. 2002 - Heart Rate and Blood Pressure Variability Biofeedback: Towards a New Generation of Psychophysiologic Protocols for Assessment and Intervention with Cardiac Patients Host: Robert P. Nolan, PhD, Director, Behavioural Cardiology Research Unit, University Health Network, Toronto, Ontario, Canada Heart rate variability (HRV), blood pressure variability (BPV), and baroreflex sensitivity (BRS) are recognized as clinically important indices of neuroregulation of cardiovascular functioning. There is an impressive evidence base to demonstrate that these features provide an independent prognostic index of risk for primary or secondary coronary events. Current evidence suggests that HRV- or BPV-biofeedback represents a new generation of psychophysiologic treatment which has the potential to enhance sympathovagal balance in the autonomic regulation of cardiovascular functioning. The starting point for this roundtable discussion will be to briefly introduce the prototypic assessment and treatment protocols that are currently being used in clinical trials of HRV- or BPV-biofeedback. Participants will be invited to discuss the following issues: (1) What are the strengths and limitations of this novel approach to the self-regulation of cardiovascular functioning? (2) What is the current evidence that HRV- or BPV-biofeedback is efficacious in facilitating autonomic regulation of cardiac function? (3) What further research is required in order to develop evidence-based psychophysiologic assessment and treatment protocols for cardiac patients? Discussion will also include an invitation to establish a consortium of co-investigators and site collaborators, for a strategic series of multicentre clinical trials of HRV- or BPV-biofeedback, particularly with subjects diagnosed with a cardiac condition that is associated with sympathetic hyperactivity (e.g. essential hypertension, or myocardial infarction). Autoimmune Conditions Presenters: Esther M. Sternberg MD, Kurt Ackerman, MD, PhD, David C. Mohr, PhD, Carolyn E. Schwartz, ScD Chairs: William R. Lovallo, PhD & Mustafa al'Absi, PhD The Mind Body Connection in Health and Disease Esther M. Sternberg MD, Director, Integrative Neural Immune Program, NIH, Bethesda, MD Neural-Immune Interactions in Health and Disease Interactions between the immune and nervous systems play an important role in susceptibility and resistance to inflammatory and infectious diseases. Most extensively studied in these interactions are cytokine-neuropeptide/neurotransmitter interactions. At a systemic level, cytokines from the periphery released during inflammation can stimulate the hypothalamic pituitary adrenal axis, which in turn, through the immunosuppressive effects of the glucocorticoids, inhibit inflammation. Recent studies indicate that glucocorticoids are immunomodulatory, causing a shift in patterns of cytokine production from a TH1 to a TH2 type pattern. Interruptions of this loop at any level and through multiple mechanisms, whether genetic, through surgical intervention or pharmacological intervention, can render an inflammatory resistant host susceptible to inflammatory disease. Over-activation of this axis, as occurs during stress, can also affect severity of infectious disease, through the immunosuppressive effects of the glucocorticoids, with the final outcome determined by the relative contribution of host inflammatory responses in the pathogenesis of the infectious illness. Other neural pathways also play a role in inflammatory disease regulation, including the sympathetic and peripheral nervous systems, which modulate inflammation at regional or local levels. These interactions have been clearly demonstrated in many animal models, across species, strains and diseases, and are also relevant to human inflammatory illness, including rheumatoid arthritis, systemic lupus erythematosus, Sjogren's syndrome, allergic asthma and atopic skin disease. New therapeutic interventions currently being developed based on this research include the use of anti-inflammatory drugs in Alzheimer's, anti-stress hormone drugs in arthritis, neurotransmitter related drugs for aging associated immunosuppression and cytokine antagonists and immune T-cells for treatment of spinal cord injury, nerve trauma and stroke. Stressful Life Events and Multiple Sclerosis Exacerbations: Potential Mechanisms Kurt Ackerman, MD, PhD, University of Pittsburgh Many studies have suggested a powerful relationship between stressful life events and the clinical disease course of autoimmune disorders. However, it has been difficult to identify potential mechanisms of this relationship and determine clinically relevant mediating and moderating factors. Recent animal and human studies of stress and multiple sclerosis (MS) may provide a model for examining these issues. In this presentation, a study will be described in which subjects with relapsing-remitting multiple sclerosis were followed in a longitudinal study of life events; autonomic, neuroendocrine, and immune responses; and physical health. The results to date suggest that stress is strongly linked to clinical MS exacerbations, with both an increased likelihood of exacerbation following stressful life events, and a shortened disease-free interval during stressful periods. Relevant mediators and moderators may include stressor severity and acuity, coping strategy, sympathetic activation and parasympathetic withdrawal, development of depression, and stage of disease. These factors will discussed as part of an overall model of prevention for stress-related autoimmune disorders. Behavioral Medicine and Multiple Sclerosis: Symptomatic Relief or Disease Modifying Therapy? David C. Mohr, PhD, University of California, San Francisco Multiple Sclerosis (MS) is associated with a variety of psychosocial problems including 50% lifetime risk of major depressive disorder and markedly decreased quality of life (QOL). In a recently completed comparative trial of three treatments for depression in MS we found significant reductions in depression and significant improvements in QOL. Assessments of immune function over the course of the study showed that successful treatment of depression was associated with significant reductions in autoimmune activity associated with MS exacerbation. We also found that over the course of a one-year follow-up, higher QOL at the end of treatment predicted lower risk of subsequent exacerbation. These findings suggest that behavioral medicine not only provides symptomatic relief, but may also be a novel disease modifying treatment. Psychosocial Factors in Adaptation to Autoimmune Disease Carolyn E. Schwartz, ScD, University of Massachusetts Medical School Positive psychosocial factors can influence patients' course of disease or well-being. I will review my own and others' work looking at the quality-of-life impact of psychosocial interventions for people with multiple sclerosis, and the surprising benefits of altruism on psychosocial outcomes. It will then describe an evolving new construct called response shift, which refers to health-related changes in individuals' internal standards, values, and conceptualizations of target constructs of interest in psychosomatic medicine. The evidence for and implications of response shift for observational and intervention research will be discussed. Cancer Chair: Norman B. Levy Corting Disaster: Abnormal Diurnal Cortisol Variation Predicts Early Breast Cancer Mortality Sandra E. Sephton, Robert Sapolsky, Helena C. Kraemer, David Spiegel, Department of Psychiatry & Behavioral Science and Department of Biological Sciences, Stanford University, Stanford, CA Presenter: David Spiegel Evidence has accumulated demonstrating a connection between psychosocial stress and support and the rate of disease progression among women with breast cancer. Laboratory studies have shown that abnormalities in stress-induced cortisol response are associated with more rapid tumor progression. Abnormalities of endocrine circadian rhythms have been observed in patients with cancer, but the prognostic value of such alterations has not previously been confirmed. These findings point to a possible role of cortisol in mediating the effects of psychosocial variables on disease progression. The association between diurnal variation of salivary cortisol and subsequent survival of the metastatic breast cancer patient was examined, and the relationship between cortisol rhythms and immunological function was investigated. Daytime salivary cortisol levels of 109 metastatic breast cancer patients were assessed at study entry on each of three consecutive days, and the slope of diurnal cortisol variation was calculated using log transformed regression analysis. The slope of diurnal cortisol was associated with subsequent survival time up to four years later. Shorter survival was noted among patients with relatively "flat" diurnal cortisol rhythms indicating lack of normal diurnal variation (Cox Proportional Hazards p = .02). These patients also had diminished natural killer (NK) cell numbers. Patients lacking diurnal variability of daytime salivary cortisol levels suffered earlier mortality. Data regarding related immune suppression will also be discussed. Dysregulation of diurnal cortisol patterns may be a mediator of more rapid breast cancer progression. This study was funded by NIMH grant MH47226, with additional funding from NCI, the MacArthur Foundation and the Fetzer Institute The Role of Natural Killer (NK) Cells in Resistance Against Cancer and the Effects of Stress on NK Cell Function Ronald B. Herberman, University of Pittsburgh Cancer Institute, Pittsburgh, PA Presenter: David Herberman NK cells are a distinct component of the immune system, having the morphology of large granular lymphocyte and the ability to mediate spontaneous cytoxic activity against cancer and series-infected cells and to secrete high levels of several cytokines. They play a major role in innate immunity, especially against the development of progression of cancer, and also protect against the establishment of metastases. In mice or rats with selective NK cell deficiency, restoration of function by adoptivo transfer of NK cells restores resistance to metastases. Similarly, in studies in cancer patients, low NK activity around the time of initial diagnosis or treatment has been correlated with poor prognosis and a higher rate of subsequent metastases. Although NK cells have spontaneous anti-tumore activity, they are also subject to considerable regulation. Cytokines such as interferon and interleukins 2, 12 or 15 stimulate their functions, and various types of stress as well as defined immunoregulatory molecules can strongly inhibit NK activity. In many psychoneuroimmunologic studies, NK cell function has been found to be particularly susceptible to alternations in function, with low NK activity resulting from either acute or chronic stress. These observations have led to the hypothesis that the ability of stress-reducing interventions to have beneficial effects in tumor-bearing individuals might be mediated at least in part by restoration of NK cell function. Results from several studies have provided some results in support of this possibility. Asthma Chair: Steve Manuck The Rising Prevalence and Morbidity of Asthma: Is Increased Stress Playing a Role? Scott T. Weiss, Harvard Medical School, Boston, MA Mechanisms of Asthma Pathogenesis: The Potential Role and Contribution of Stress William Busse, University of Wisconsin School of Medicine, Madison, WI Psychosocial and Behavioral Risk Factors in Asthma Management Cynthia Rand, Johns Hopkins School of Medicine, Baltimore, MD