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

McEwen BS - Dialogues Clin Neurosci (2006)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Harold and Margaret Milliken Hatch Laboratory of Neuroendocrinology, The Rockefeller University, New York, NY 10021, USA. mcewen@mail.rockefeller.edu

ABSTRACT
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 notjust 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.

Show MeSH

Related in: MedlinePlus

Four types of allostatic load. The top panel illustrates the normal allostatic response, in which a response is initiated by a stressor, sustained for an appropriate interval, and then turned off. The remaining panels illustrate four conditions that lead to allostatic load: top left- repeated “hits” from multiple stressors; top right- lack of adaptation; bottom left- prolonged response due to delayed shut down; and bottom right - inadequate response that leads to compensatory hyperactivity of other mediators (eg, inadequate secretion of glucocorticoid, resulting in increased levels of cytokines that are normally counter-regulated by glucocorticoids). Reproduced from reference 1 ; McEwen BS. Protective and damaging effects of stress mediators. N Engl J Med. 1998; 338:171-179. Copyright © Massachusetts Medical Society 1998.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC3181832&req=5

DialoguesClinNeurosci-8-367-g001: Four types of allostatic load. The top panel illustrates the normal allostatic response, in which a response is initiated by a stressor, sustained for an appropriate interval, and then turned off. The remaining panels illustrate four conditions that lead to allostatic load: top left- repeated “hits” from multiple stressors; top right- lack of adaptation; bottom left- prolonged response due to delayed shut down; and bottom right - inadequate response that leads to compensatory hyperactivity of other mediators (eg, inadequate secretion of glucocorticoid, resulting in increased levels of cytokines that are normally counter-regulated by glucocorticoids). Reproduced from reference 1 ; McEwen BS. Protective and damaging effects of stress mediators. N Engl J Med. 1998; 338:171-179. Copyright © Massachusetts Medical Society 1998.

Mentions: “Stress” is an ambiguous term, and has connotations that make it less useful in understanding how the body handles the events that are stressful. Insight into these processes can lead to a better understanding of how best to intervene, a topic that will be discussed at the end of this article. There are two sides to this story1: on the one hand, the body responds to almost any event or challenge by releasing chemical mediators -eg, catecholamines that increase heart rate and blood pressure -that help us cope with the situation; on the other hand, chronic elevation of these same mediators -eg, chronically increased heart rate and blood pressure -produce chronic wear and tear on the cardiovascular system that can result, over time, in disorders such as strokes and heart attacks. For this reason, the term “allostasis” was introduced by Sterling and Eyer2 to refer to the active process by which the body responds to daily events and maintains homeostasis (allostasis literally means “achieving stability through change”). Because chronically increased allostasis can lead to disease, we introduced the term “allostatic load or overload” to refer to the wear and tear that results from either too much stress or from inefficient management of allostasis, eg, not turning off the response when it is no longer needed.1,3,4 Other forms of allostatic load are summarized in Figure 1, and involve not turning on an adequate response in the first place, or not habituating to the recurrence of the same stressor, and thus dampening the allostatic response.


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

McEwen BS - Dialogues Clin Neurosci (2006)

Four types of allostatic load. The top panel illustrates the normal allostatic response, in which a response is initiated by a stressor, sustained for an appropriate interval, and then turned off. The remaining panels illustrate four conditions that lead to allostatic load: top left- repeated “hits” from multiple stressors; top right- lack of adaptation; bottom left- prolonged response due to delayed shut down; and bottom right - inadequate response that leads to compensatory hyperactivity of other mediators (eg, inadequate secretion of glucocorticoid, resulting in increased levels of cytokines that are normally counter-regulated by glucocorticoids). Reproduced from reference 1 ; McEwen BS. Protective and damaging effects of stress mediators. N Engl J Med. 1998; 338:171-179. Copyright © Massachusetts Medical Society 1998.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3181832&req=5

DialoguesClinNeurosci-8-367-g001: Four types of allostatic load. The top panel illustrates the normal allostatic response, in which a response is initiated by a stressor, sustained for an appropriate interval, and then turned off. The remaining panels illustrate four conditions that lead to allostatic load: top left- repeated “hits” from multiple stressors; top right- lack of adaptation; bottom left- prolonged response due to delayed shut down; and bottom right - inadequate response that leads to compensatory hyperactivity of other mediators (eg, inadequate secretion of glucocorticoid, resulting in increased levels of cytokines that are normally counter-regulated by glucocorticoids). Reproduced from reference 1 ; McEwen BS. Protective and damaging effects of stress mediators. N Engl J Med. 1998; 338:171-179. Copyright © Massachusetts Medical Society 1998.
Mentions: “Stress” is an ambiguous term, and has connotations that make it less useful in understanding how the body handles the events that are stressful. Insight into these processes can lead to a better understanding of how best to intervene, a topic that will be discussed at the end of this article. There are two sides to this story1: on the one hand, the body responds to almost any event or challenge by releasing chemical mediators -eg, catecholamines that increase heart rate and blood pressure -that help us cope with the situation; on the other hand, chronic elevation of these same mediators -eg, chronically increased heart rate and blood pressure -produce chronic wear and tear on the cardiovascular system that can result, over time, in disorders such as strokes and heart attacks. For this reason, the term “allostasis” was introduced by Sterling and Eyer2 to refer to the active process by which the body responds to daily events and maintains homeostasis (allostasis literally means “achieving stability through change”). Because chronically increased allostasis can lead to disease, we introduced the term “allostatic load or overload” to refer to the wear and tear that results from either too much stress or from inefficient management of allostasis, eg, not turning off the response when it is no longer needed.1,3,4 Other forms of allostatic load are summarized in Figure 1, and involve not turning on an adequate response in the first place, or not habituating to the recurrence of the same stressor, and thus dampening the allostatic response.

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Harold and Margaret Milliken Hatch Laboratory of Neuroendocrinology, The Rockefeller University, New York, NY 10021, USA. mcewen@mail.rockefeller.edu

ABSTRACT
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 notjust 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.

Show MeSH
Related in: MedlinePlus