T H E   N I H    C A T A L Y S T      M A Y   –  J U N E   2001




by Esther Sternberg, Director
Integrative Neural Immune Program


Collegial Interactions (left to right): Robert Rose, conference co-chair and director of the MacArthur Foundation Mind-Body Network; Esther Sternberg, conference co-chair and director of the NIMH Intramural Integrative Neural Immune Program (and author of this article); and acting NIH director Ruth Kirschstein.
In his introductory remarks, Rose emphasized the importance of skeptical enthusiasm and solid scientific research to further the field of mind-body science. Much of the data presented during the meeting grew out of interdisciplinary projects jointly funded by NIH and the MacArthur Foundation Mind-Body Network.
In her conference-opening remarks, Kirschstein emphasized the increasing importance of interdisciplinary research, pointing to several NIH interdisciplinary initiatives in mind-body science research, including the university-based Mind-Body Centers funded through OBSSR and the newly established intramural Integrative Neural Immune Program at NIH.

The Science of Mind-Body Interactions conference, held at Masur Auditorium March 26–28, 2001, was hosted by the NIH Intramural Integrative Neural Immune Program (see box) and cosponsored by the John D. and Catherine T. MacArthur Foundation, NIMH, NINDS, and 13 other NIH institutes, centers, and offices: NCI, NHLBI, NIA, NIAID, NIAMS, NIDA, NIDCR, NLM, NCCAM, ORWH, OBSSR, OIR, and the National Center on Sleep Disorders Research, NHLBI. Hailed as a "demonstration of a paradigm shift in medicine," * the conference was attended by 500–and viewed simultaneously by 1,200 people in the United States and Canada, thanks to the web group at CIT.

Concepts embedded in the popular culture for thousands of years were recast in the bright light of science earlier this year at a three-day conference here—the first of its kind at NIH to address the effects of such variables as individual social interactions and psychological responses on the molecular and cellular mechanisms of disease processes.

Emphasizing intervening brain pathways, molecules, and hormones, the conference on the "Science of Mind-Body Interactions" provided scientific mechanisms from the fields of neurobiology, immunology, and endocrinology to explain how the "social world gets under our skin"—a theme of the conference coined by Harvard science historian and MacArthur Foundation Mind-Body Network member, Anne Harrington.

Gerald Fischbach, former NINDS director and currently vice president for health and medical sciences and dean of medicine, Columbia University, New York, returned to NIH to present his views on integrative research. During his tenure here, Fischbach was instrumental in supporting both the MacArthur/NIH Science of Mind Body Interactions conference and the Integrative Neural Immune Program.

Research directly connecting health effects observed at an epidemiological level to individual psychological and physiological health variables is not abundant. But conference speakers systematically highlighted cutting-edge research on the neurobiology of emotions; neural and neuroendocrine factors affecting autoimmune, inflammatory, allergic, and infectious diseases; and the very long arm of sleep or the lack of it.

Nancy Adler (University of California at San Francisco), director of the MacArthur Foundation Research Network on Socioeconomic Status (SES) and Health, presented evidence that lower SES is associated in a dose-related manner with adverse health outcomes. Among those SES factors that compromise health are poor living conditions, exposures to toxins and environmental irritants, stress, depression, and lack of medical care and follow-up. Most importantly, Adler said, perceived inequality leading to alienation and isolation could be factors in initiating a chain of negative health effects.


The notion that social isolation predicts higher morbidity and mortality, especially in elderly, poor, and minority populations, was dramatically supported in three separate studies of the cardiovascular status of lonely individuals.

Reported by John Cacioppo (University of Chicago) and Julian Thayer (NIA, Baltimore), all three studies linked loneliness to greater sympathetic nervous system reactivity, higher blood pressure, or greater perceived stress. Components of this "threat" pattern (high impedance, low cardiac output), as opposed to "challenge" pattern (high cardiac output, low peripheral resistance) of cardiac reactivity, were seen in populations as varied as 2,600 undergraduate students, elderly individuals in Chicago, and elderly, isolated African Americans in inner-city Baltimore.

Preliminary findings from another study by Cacioppo and David Spiegel (Stanford [Calif.] University) provided additional support that feeling lonely can change psychological response patterns: When subjects who were not lonely were hypnotized into a lonely state, they experienced a shift in psychological variables from a challenge pattern to the threat pattern observed in truly lonely people.

Martha McClintock (University of Chicago) presented animal data showing that group-housed rats lived 40 percent longer than isolated animals. The cause of death in the isolated animals was related to opportunistic infections and tumors, suggesting that state of the organism rather than type of pathogen was a key factor.


That emotional responses can be viewed as a transduction process by which social variables might affect health was further explored in a session on the neurobiology of emotions, chaired by Richard Davidson (University of Wisconsin at Madison). Davidson presented data combining the tools of PET and fMRI neuroimaging and EEG brain electrical activity mapping to show that differences in emotional circuitry are linked to differences in brain approach-and-withdrawal systems and differences in emotional style.

There is no single emotional center in the brain. Rather, many centers work together to detect conflict and recruit response centers that then generate behaviors leading to mood alteration and ultimately to goal achievement.

Large-scale longitudinal studies carried out over several decades in Wisconsin show that individual differences in patterns of brain electrical activity, blood flow, and metabolism are associated with different emotional response patterns and differences in host resiliency.

Michael Meaney (McGill University, Montreal, Quebec) presented evidence that factors in early development, including maternal-offspring interactions, can influence hormonal and neuronal pathways at a molecular and cellular level and result in permanent alterations of the set-point of the hormonal stress response.

John Sheridan (Ohio State University in Columbus) reported that mice subjected to the stress of social reorganization experienced higher mortality from viral infection and reactivation of herpesvirus. These outcomes were related to impaired immune responses and cell trafficking and changes in immune molecules that orchestrate these responses.

Perchance To Dream

The final session focused on an often- ignored fact of life that may account for many of the deleterious effects of emotions and stress on health: lack of sleep. This session, chaired by Eve Van Cauter (University of Chicago), surveyed the diverse consequences of sleep deprivation—from increased risk of motor vehicle accidents as a result of impaired cognition and motor skills and increased irritability to an array of hormonal changes (including increased blood cortisol, decreased growth hormone, and induced insulin resistance) that can impair immune function, retard growth, accelerate aging, and compromise sugar metabolism to the level of diabetes.

Interactive panel discussions throughout the conference, which engaged the audience in lively debate, also served as forums for related issues, including findings with implications for new therapeutic approaches. Among these were the use of an antidepressant phosphodiesterase inhibitor for immune suppression in the autoimmune disease multiple sclerosis and the therapeutic potential for pain management that can be deduced from the discovery of chemokine-opiate receptor interactions.

The archived videocast of the conference is accessible online.

* Uttered by Emeran Mayer, director of the UCLA Mind Body CRC and CURE Neuroenteric Disease Program, who seemed to speak for many.

Integrative Neural Immune Program

The NIH Integrative Neural Immune Program is designed to foster intramural interdisciplinary research in the field of neural-immune interactions, the biological basis of the so-called "mind-body" interaction.

The program’s structure also accommodates interagency, university, and private sector partnerships.

The program encompasses the study of molecular, cellular, and neuroanatomical mechanisms of neural-immune interactions, as well as systems-level analysis of communications between the central nervous, endocrine, and immune systems.

This research has relevance to the role of the immune system in neuronal cell death and repair, neuronal development and plasticity, and the role of the nervous and neuroendocrine systems in susceptibility and resistance to autoimmune, inflammatory, allergic, and infectious diseases.

Basic research in this area has clinical implications for understanding the pathogenesis of and developing treatments for diseases such as multiple sclerosis, Alzheimer’s, AIDS, stroke, nerve trauma, and brain tumors.

It will inform our understanding of the effects of depression, stress, and beliefs on immune-mediated conditions, such as arthritis and allergic and infectious diseases.

This intramural research program will bridge neurobiology and immunology laboratories and related clinical branches through a series of cores—Administrative Core, Virtual Core, Scientific Communications Core, Laboratory Core, and Training Core.

A series of on-campus neural-immune lectures and intramural-extramural workshops and conferences is taking shape to foster interactions among participating labs, define the current state of the field, and create new research agendas. (The first major gathering was the "Science of Mind-Body Interactions" conference.)

Resources to facilitate interdisciplinary collaborative research, as well as a neural-immune training program, should well serve the program’s ultimate goal: to enable researchers to rapidly address cutting-edge multidisciplinary research questions and to translate basic research findings into tangible clinical health outcomes. More than 85 scientists currently participate in the program.

Directed by Esther Sternberg, chief of the NIMH Neuroendocrine Immunology and Behavior Section, the program is based at NIMH and is co-sponsored by NINDS, NCI, NIA, NIAID, and NIAMS and the OIR.



Return to Table of Contents