Abstract
Stress begins in the brain and affects the brain, as well as the rest of the body. Acute stress responses promote adaptation and survival via responses of neural, cardiovascular, autonomic, immune and metabolic systems. Chronic stress can promote and exacerbate pathophysiology through the same systems that are dysregulated. The burden of chronic stress and accompanying changes in personal behaviors (smoking, eating too much, drinking, poor quality sleep; otherwise referred to as “lifestyle”) is called allostatic overload. Brain regions such as hippocampus, prefrontal cortex and amygdala respond to acute and chronic stress and show changes in morphology and chemistry that are largely reversible if the chronic stress lasts for weeks. However, it is not clear whether prolonged stress for many months or years may have irreversible effects on the brain. The adaptive plasticity of chronic stress involves many mediators, including glucocorticoids, excitatory amino acids, endogenous factors such as brain neurotrophic factor (BDNF), polysialated neural cell adhesion molecule (PSA-NCAM) and tissue plasminogen activator (tPA). The role of this stress-induced remodeling of neural circuitry is discussed in relation to psychiatric illnesses, as well as chronic stress and the concept of top-down regulation of cognitive, autonomic and neuroendocrine function. This concept leads to a different way of regarding more holistic manipulations, such as physical activity and social support as an important complement to pharmaceutical therapy in treatment of the common phenomenon of being “stressed out”. Policies of government and the private sector play an important role in this top-down view of minimizing the burden of chronic stress and related lifestyle (i.e. allostatic overload).
Introduction
The brain is the central organ of the stress response and determines what is stressful, as well as the behavioral and physiological responses to potential and actual stressors. The brain is also a target of stress and it changes structurally and chemically in response to both acute and chronic stressors. Glucocorticoids play a role in these changes, but there are other mediators as well. Although glucocorticoids and catecholamines are the two defining hormones of the “fight or flight” stress response, there are many other mediators, such as pro- and anti-inflammatory cytokines and the parasympathetic nervous system, that are also involved in the adaptation to stressors, as well as in the negative impact of chronic stress, known in every day language as being “stressed out”.
Indeed, there are important differences in the effects of acute and chronic stress, as well as differences in the consequences of acute and chronic treatment with glucocorticoids. This review explores these topics in the context of discussing the concepts of allostasis and allostatic load and overload and what they say about brain and body adaptation to acute and chronic stressors, as well as what can be done to reduce the negative aspects of allostatic overload. The principal theme of the discussion of interventions is how to take advantage of the central role that the brain plays in perceiving, responding to and adapting or not adapting efficiently to experiences and events throughout the lifecourse.
Interventions: conventional vs top down
If being “stressed out” has such pervasive long-term effects on the brain as well as the body, what are the ways to reduce the negative consequences? The answers are simple and obvious but often difficult to achieve and they involve not only individual behaviors but also the ways in which people’s lives are shaped by policies of government and the private sector.
From the standpoint of the individual, it seems obvious that a major goal should be to try to improve sleep quality and quantity, to have good social support and a positive outlook on life, to have positive self-esteem, to maintain a healthy diet, to avoid smoking and to engage in regular moderate physical activity. Concerning physical activity, it is not necessary to become an extreme athlete, and seemingly any amount of moderate physical activity helps (Bernadet, 1995; Rovio et al., 2005).
From the standpoint of organization of society, the goal should be to create incentives at home and in work situations and build community services and opportunities that encourage the development of the beneficial individual lifestyle practices. The Acheson Report (Acheson, 1998) from the United Kingdom in 1998 recognized that no public policy should be enacted without considering the implications for health of all citizens. Thus basic education, housing, taxation, setting of a minimum wage, and addressing occupational health and safety and environmental pollution regulations are all likely to affect health via a myriad of mechanisms. At the same time, providing higher quality food and making it affordable and accessible in poor as well as affluent neighborhoods is necessary for people to eat better, providing they also learn what types of food to eat. Likewise, making neighborhood safer and more congenial and supportive (Sampson et al., 1997) can improve opportunities for positive social interactions and increased recreational physical activity. However, governmental policies are not the only way to reduce allostatic load. For example, businesses that encourage healthy lifestyle practices among their employees are likely to gain reduced health insurance costs and possibly a more loyal workforce (Aldana, 2001; Pelletier, 2001; Whitmer et al., 2003).
These are the “top down” strategies that are likely to work via higher cognitive brain areas and their downstream effects on many processes. As simple as the solutions seem to be, changing behavior and solving problems that cause stress at work and at home is often difficult and may require professional help on the personal level, or even a change of job or profession. Yet these are important goals because the prevention of later disease is very important for full enjoyment of life and also to reduce the financial burden on the individual and on society.
Nevertheless, many people often lack the proactive, long term view of themselves and/or feel that they must maintain a stressful lifestyle and, if they deal with these issues at all, they want to treat their problems with a pill. Are there any medications to treat being stressed out? In fact, there are many useful pharmaceutical agents: sleeping pills, anxiolytics, beta blockers and antidepressants are all drugs that are used to counteract some of the problems associated with being stressed out. Likewise, drugs that reduce oxidative stress or inflammation, block cholesterol synthesis or absorption and treat insulin resistance or chronic pain and can help deal with the metabolic and neurologic consequences of being stressed out. All are valuable to some degree, and yet each one has its side effects and limitations that are based in part on the fact that all of the systems that are dysregulated in allostatic overload are also systems that interact with each other and perform normal functions when properly regulated. Because of the non-linearity of the systems of allostasis, the consequences of any drug treatment may be either to inhibit the beneficial effects of the systems in question or to perturb other systems that interact with it in a direction that promotes an unwanted side effect. So the best solution would seem to be not to rely solely on such medications and find ways to change personal behaviors in a positive direction. Motivation and decision making and perseverance are all functions of the brain!
Acknowledgments
The author is indebted to many talented students and postdoctoral fellows and colleagues in many disciplines and in many parts of the world, including the MacArthur Research Network on Socioeconomic Status and Health. Research support: NIH Grants MH41256 and5P50 MH58911