The brain is the key organ of the response to stress because it determines what is threatening and, therefore, potentially stressful, as well as the physiological and behavioral responses which can be either adaptive or damaging. Stress involves two-way communication between the brain and the cardiovascular, immune, and other systems via neural and endocrine mechanisms. Beyond the "flight-or-fight" response to acute stress, there are events in daily life that produce a type of chronic stress and lead over time to wear and tear on the body ("allostatic load"). Yet, hormones associated with stress protect the body in the short-run and promote adaptation ("allostasis"). The brain is a target of stress, and the hippocampus was the first brain region, besides the hypothalamus, to be recognized as a target of glucocorticoids. Stress and stress hormones produce both adaptive and maladaptive effects on this brain region throughout the life course. Early life events influence life-long patterns of emotionality and stress responsiveness and alter the rate of brain and body aging. The hippocampus, amygdala, and prefrontal cortex undergo stress-induced structural remodeling, which alters behavioral and physiological responses. As an adjunct to pharmaceutical therapy, social and behavioral interventions such as regular physical activity and social support reduce the chronic stress burden and benefit brain and body health and resilience.

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Physiology and Neurobiology of Stress and Adaptation: Central Role of the Brain

Central effects of stress hormones in health and disease: understanding the protective and damaging effects of stress and stress mediators

The brain is the key organ of stress reactivity, coping, and recovery processes. Within the brain, a distributed neural circuitry determines what is threatening and thus stressful to the individual. Instrumental brain systems of this circuitry include the hippocampus, amygdala, and areas of the prefrontal cortex. Together, these systems regulate physiological and behavioral stress processes, which can be adaptive in the short-term and maladaptive in the long-term. Importantly, such stress processes arise from bidirectional patterns of communication between the brain and the autonomic, cardiovascular, and immune systems via neural and endocrine mechanisms underpinning cognition, experience, and behavior. In one respect, these bidirectional stress mechanisms are protective in that they promote short-term adaptation (allostasis). In another respect, however, these stress mechanisms can lead to a long-term dysregulation of allostasis in that they promote maladaptive wear-and-tear on the body and brain under chronically stressful conditions (allostatic load), compromising stress resiliency and health. This review focuses specifically on the links between stress-related processes embedded within the social environment and embodied within the brain, which is viewed as the central mediator and target of allostasis and allostatic load.

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Central role of the brain in stress and adaptation: links to socioeconomic status, health, and disease.

The brain is the key organ of stress processes. It determines what individuals will experience as stressful, it orchestrates how individuals will cope with stressful experiences, and it changes both functionally and structurally as a result of stressful experiences. Within the brain, a distributed, dynamic, and plastic neural circuitry coordinates, monitors, and calibrates behavioral and physiological stress response systems to meet the demands imposed by particular stressors. These allodynamic processes can be adaptive in the short term (allostasis) and maladaptive in the long term (allostatic load). Critically, these processes involve bidirectional signaling between the brain and body. Consequently, allostasis and allostatic load can jointly affect vulnerability to brain-dependent and stress-related mental and physical health conditions. This review focuses on the role of brain plasticity in adaptation to, and pathophysiology resulting from, stressful experiences. It also considers interventions to prev...

Stress- and Allostasis-Induced Brain Plasticity

The mind involves the whole body, and two-way communication between the brain and the cardiovascular, immune, and other systems via neural and endocrine mechanisms Stress is a condition of the mind-body interaction, and a factor in the expression of disease that differs among individuals It is not just the dramatic stressful events that exact their toll, but rather the many events of daily life that elevate and sustain activities of physiological systems and cause sleep deprivation, overeating, and other health-damaging behaviors, producing the feeling of being “stressed out” Over time, this results in wear and tear on the body, which is called “allostatic load,” and it reflects not only the impact of life experiences but also of genetic load, individual lifestyle habits reflecting items such as diet, exercise, and substance abuse, and developmental experiences that set life-long patterns of behavior and physiological reactivity Hormones associated with stress and allostatic load protect the body in the short run and promote adaptation by the process known as allostasis, but in the long run allostatic load causes changes in the body that can lead to disease The brain is the key organ of stress, allostasis, and allostatic load, because it determines what is threatening and therefore stressful, and also determines the physiological and behavioral responses Brain regions such as the hippocampus, amygdala, and prefrontal cortex respond to acute and chronic stress by undergoing structural remodeling, which alters behavioral and physiological responses Translational studies in humans with structural and functional imaging reveal smaller hippocampal volume in stress-related conditions, such as mild cognitive impairment in aging and prolonged major depressive illness, as well as in individuals with low self-esteem Alterations in amygdala and prefrontal cortex are also reported Besides Pharmaceuticals, approaches to alleviate chronic stress and reduce allostatic load and the incidence of diseases of modern life include lifestyle change, and policies of government and business that would improve the ability of individuals to reduce their own chronic stress burden

Protective and damaging effects of stress mediators: central role of the brain.

Purpose. This article is the fifth in a series of critical reviews of the clinical effectiveness and cost-effectiveness studies of comprehensive, multifactorial health promotion and disease management programs conducted in worksites. As with the previous reviews, the purpose of this article is to review and assess the randomized control trials that have focused on both clinical and cost outcomes of worksite health promotion and disease management programs. For this current review, a new category of quasi-experimental studies has been added because this represents a major new trend in such interventions over the last 2 years. Comprehensive worksite programs are those that provide an ongoing, integrated program of health promotion and disease prevention that integrates specific components into a coherent, ongoing program that is consistent with corporate objectives and includes program evaluations of both clinical and cost outcomes. Data Sources. A comprehensive search was conducted using a multist...

A Review and Analysis of the Clinical- and Cost-effectiveness Studies of Comprehensive Health Promotion and Disease Management Programs at the Worksite: 1998–2000 Update

Objective To assess the status of managed care and insurance coverage of complementary and alternative medicine (CAM) and the integration of such services into managed care. Data sources A literature review and information search were conducted to determine which new insurers had special policies for CAM from 1999 to 2000. Telephone interviews were conducted with a sample of 6 new managed care organizations (MCOs) or insurers identified in 2000 and a nonrepresentative cohort of 4 of the original 18 MCOs and insurers who responded both to the original survey in 1997 and again in 1998 to determine trends. Study selection This study constitutes the results of the third year of an ongoing annual survey. For the year 2000, a total of 14 new companies were identified as offering some CAM coverage. Survey results were analyzed for 6 of these who responded to the current survey as well as the results of the cohort mentioned above. Data extraction and synthesis Most of the insurers interviewed offer some coverage for the following: nutrition counseling, biofeedback psychotherapy, acupuncture, preventive medicine, chiropractic, osteopathy, and physical therapy. All new companies indicated that market demand was a primary motivator for covering CAM. Factors determining whether insurers would offer coverage for additional therapies included potential cost-effectiveness, consumer interest, and demonstrable clinical efficacy. Among the most common obstacles listed for incorporating CAM into mainstream healthcare were lack of research on clinical or cost-effectiveness, economics, ignorance about CAM, provider competition, and lack of standards of practice. Conclusion Consumer demand for CAM is motivating more MCOs and insurance companies to assess the clinical and cost benefits of incorporating CAM. Outcomes studies for both conventional and CAM therapies are needed to help create a healthcare system based on treatments that work, whether they are conventional, complementary, alternative, or integrative medicine.

Integration and reimbursement of complementary and alternative medicine by managed care and insurance providers: 2000 update and cohort analysis.

For more than 25 years, health promotion and disease management interventions have been conducted by large employers in the United States. Today there are more than 100 studies of such multifactorial, comprehensive interventions that all demonstrate positive clinical outcomes. For those interventions that have also been evaluated for return on investment, all but one have demonstrated cost-effectiveness. This article is an evidence-based overview of the clinical and cost outcomes research to elaborate on the insights gained from this research in the areas of implementation and evaluation of such programs; integration of health promotion and disease management programs into conventional, occupational medicine; accessing difficult to reach populations, such as mobile workers, retirees, and/or dependents; areas of potential conflict of interest and privacy/confidentiality issues; health consequences of downsizing and job strain; and, finally, recommendations for improved integration and evaluation of such programs for both clinical and cost outcomes. With medical costs rapidly escalating again on a global scale, these interventions with evidence of both clinical and cost outcomes can provide the foundation to improve the health, performance, and productivity of both individuals and their corporations.

Kenneth R. Pelletier

Papers

A Review and Analysis of the Clinical- and Cost-effectiveness Studies of Comprehensive Health Promotion and Disease Management Programs at the Worksite: 1998–2000 Update

Integration and reimbursement of complementary and alternative medicine by managed care and insurance providers: 2000 update and cohort analysis.

International Collaboration in Health Promotion and Disease Management: Implications of U.S. Health Promotion Efforts on Japan's Health Care System:

Conventional and integrative medicine – evidence based? Sorting fact from fiction

The selection effects of the inclusion of a chiropractic benefit on the patient population of a managed health care organization.