Basic mechanisms of, and treatment targets for, stress-related disorders

2020 ◽  
pp. 829-839
Author(s):  
Bruce S. McEwen
Keyword(s):  
Early Life ◽  
Allostatic Load ◽  
Life Experiences ◽  
The Body ◽  
The Social ◽  
Wear And Tear ◽  
Short Run ◽  
Social And Physical Environment ◽  
The Impact ◽  
The Brain

The response to the social and physical environment involves two-way communication between the brain and the body and epigenetic adaptation (‘allostasis’) via mediators of the cardiovascular, immune, metabolic, neuroendocrine, and neural mechanisms. Chronic stress causes wear and tear on the brain and body (‘allostatic load and overload’), reflecting also the impact of health-damaging behaviours and lasting effects of early life experiences interacting with genetic predispositions. Hormonal and other mediators of allostasis promote adaptation in the short run but cause allostatic load/overload when they are overused or dysregulated. The brain is key because it determines what is threatening and the physiological and behavioural responses, while showing structural remodelling that affects its function. Besides pharmaceuticals, there are ‘top–down’ interventions, like physical activity, that engage ‘the wisdom of the body’ to change itself, as well as the impact of policies of government and business that encourage individuals to manage their own lives and promote increased ‘healthspan’.

scholarly journals The impact of racially-motivated housing discrimination on allostatic load among Indigenous university students

2019 ◽  
Author(s):  
Cheryl Currie ◽  
Takara A. Motz ◽  
Jennifer L Copeland
Keyword(s):  
Immune System ◽  
University Students ◽  
Allostatic Load ◽  
The Body ◽  
Linear Regression Models ◽  
Cross Sectional ◽  
Housing Discrimination ◽  
The Past ◽  
Wear And Tear ◽  
The Impact

Abstract Background Allostatic load (AL) is an aggregate measure of wear and tear on the body due to the chronic activation of the stress response system. The goal of this study was to examine the association between racially-motivated housing discrimination and AL score within a sample of Indigenous university students.Methods Data for this cross-sectional study were collected from Indigenous adults attending university in a small city in western Canada between 2015 and 2017 ( N = 104; Mean age = 27.8 years). An item adapted from the Experience of Discrimination Scale was to assess racially-motivated housing discrimination in the past 12 months. AL was measured as a composite of 7 biomarkers assessing neuroendocrine, cardiovascular, metabolic, and immune system function. Bias-corrected and accelerated bootstrapped linear regression models were used to examine associations adjusting for age, income, parenthood, and other situations in which discrimination had been experienced.Results Indigenous university students who experienced racially-motivated housing discrimination in the past year (16.8% of the sample) had an average AL score of approximately 4, which was almost double that of their peers who had not. In an adjusted model. racially-motivated housing discrimination was associated with a-1.5 point increase in AL score. This model explained 35% of the adjusted variance in AL score, of which racially-motivated housing discrimination explained 24% ( R 2 Change = 0.24, F Change = 32.52, Sig. F Change p <0.001).Conclusions Indigenous adults who experienced racially-motivated housing discrimination in the past year had early and more pronounced wear and tear on neuroendocrine, cardiovascular, metabolic, and immune system functioning in young and middle adulthood than Indigenous peers who did not. These findings combine with others to highlight the need for increased efforts to prevent racially-motivated housing discrimination in urban centres.

scholarly journals Can Biological Markers Partially Explain the Link Between the Social Environment and Oral Health?

2018 ◽  
Vol 20 (2) ◽  
pp. 10-15
Author(s):  
Cristina Barboza Solís MSc, PhD
Keyword(s):  
Oral Health ◽  
Health Inequalities ◽  
Biological Markers ◽  
Allostatic Load ◽  
Public Health Research ◽  
The Body ◽  
Adult Health ◽  
The Social ◽  
Wear And Tear ◽  
New Perspective

Understanding how the social world affects humans´ health by “getting under the skin” and penetrating the cells, organs and physiological systems of the body is a key tenet in public health research. Here, we propose the idea that socioeconomic position (SEP) can be biologically embodied, potentially leading to the production of health inequalities in oral health across population groups. Recent studies show that being exposed to chronic stress across the life course could impact our health. Allostatic load (AL) is a composite biological measure of overall physiological wear-and-tear that could allow a better understanding of the potential biological pathways playing a role in the construction of the social gradient in adult health. However, to use biological measures to better understand the mechanisms that construct health inequalities in oral health has not been tested systematically. The purposes of this New Perspective is to discuss the value of using composite biological markers, such as AL, to analyze oral health. This can allow a better understanding of the mechanisms leading to health inequalities in oral health, and add some valuable information for implementing health interventions.

scholarly journals 004.From molecules to mind: stress, allostasis and integration of brain and body

2004 ◽  
Vol 16 (9) ◽  
pp. 4
Author(s):  
B. McEwen
Keyword(s):  
Life Style ◽  
Allostatic Load ◽  
The Body ◽  
Stressful Events ◽  
Whole Body ◽  
Human Society ◽  
Wear And Tear ◽  
The Mind ◽  
The Impact ◽  
Physiological Systems

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 and a factor in the expression of disease that differs among individuals. A broader view is that it is not just the dramatic stressful events that exact their toll but rather the many events of daily life that elevates activities of physiological systems so as to cause some measure of wear and tear. We call this wear and tear 'allostatic load', and it reflects not only the impact of life experiences but also genetic load' individual life-style habits reflecting items such as diet, exercise and substance abuse' and developmental experiences that set life-long patterns of behavior and physiological reactivity (1). Hormones associated with stress and allostatic load protect the body in the short-run and promote adaptation, but the long run allostatic load causes changes in the body that lead to disease. This will be illustrated for the immune system and brain regions involved in stress, fear and cognition (e.g. hippocampus, amygdala and prefrontal cortex). Besides developmental influences associated with mother–infant interactions, the most potent of stressors in adult life are those arising from competitive interactions between animals of the same species, leading to the formation of dominance hierarchies. Psychosocial stress of this type not only impairs cognitive function of lower ranking animals, but it can also promote disease (e.g. atherosclerosis) among those vying for the dominant position, as well as depressive illness. Social ordering in human society is also associated with gradients of disease, with an increasing frequency or mortality and morbidity as one descends the scale of socioeconomic status (SES) that reflects both income and education. Although the causes of these gradients of health are very complex, they are likely to reflect, with increasing frequency at the lower end of the scale, the cumulative burden of coping with limited resources and negative life events as well as differences in life style, and the allostatic load that this burden places on the physiological systems involved in adaptation and coping. (1) McEwen, B.S. (1998) Protective and damaging effects of stress mediators. New England J. Med. 238, 171–179.

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

2007 ◽  
Vol 87 (3) ◽  
pp. 873-904 ◽  
Author(s):  
Bruce S. McEwen
Keyword(s):  
Chronic Stress ◽  
Brain Region ◽  
Behavioral Interventions ◽  
Allostatic Load ◽  
Acute Stress ◽  
Stress Hormones ◽  
The Body ◽  
Pharmaceutical Therapy ◽  
Short Run ◽  
The Brain

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.

scholarly journals Can Biological Markers Partially Explain the Link Between the Social Environment and Oral Health?

2018 ◽  
Vol 20 (2) ◽  
pp. 10-15
Author(s):  
Cristina Barboza Solís MSc, PhD
Keyword(s):  
Oral Health ◽  
Health Inequalities ◽  
Biological Markers ◽  
Allostatic Load ◽  
Public Health Research ◽  
The Body ◽  
Adult Health ◽  
The Social ◽  
Wear And Tear ◽  
New Perspective

Understanding how the social world affects humans´ health by “getting under the skin” and penetrating the cells, organs and physiological systems of the body is a key tenet in public health research. Here, we propose the idea that socioeconomic position (SEP) can be biologically embodied, potentially leading to the production of health inequalities in oral health across population groups. Recent studies show that being exposed to chronic stress across the life course could impact our health. Allostatic load (AL) is a composite biological measure of overall physiological wear-and-tear that could allow a better understanding of the potential biological pathways playing a role in the construction of the social gradient in adult health. However, to use biological measures to better understand the mechanisms that construct health inequalities in oral health has not been tested systematically. The purposes of this New Perspective is to discuss the value of using composite biological markers, such as AL, to analyze oral health. This can allow a better understanding of the mechanisms leading to health inequalities in oral health, and add some valuable information for implementing health interventions.

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

2006 ◽  
Vol 8 (4) ◽  
pp. 367-381 ◽  
Keyword(s):  
Prefrontal Cortex ◽  
Chronic Stress ◽  
Allostatic Load ◽  
The Body ◽  
Stressful Events ◽  
Whole Body ◽  
Acute And Chronic Stress ◽  
The Mind ◽  
The Impact ◽  
The Brain

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.

Allostasis and neuroprogression in major psychiatric disorders

2019 ◽  
pp. 5-20
Author(s):  
Iria Grande ◽  
Flávio Kapczinski ◽  
Sebastián Camino ◽  
Gustavo Vázquez ◽  
Eduard Vieta
Keyword(s):  
Psychiatric Disorders ◽  
Affective Disorders ◽  
Allostatic Load ◽  
Unipolar Depression ◽  
Progressive Increase ◽  
The Body ◽  
Accelerated Ageing ◽  
Psychiatric Illnesses ◽  
Wear And Tear ◽  
The Brain

The hypothesis of allostasis may be a pertinent model to explain the course of psychiatric illnesses by means of stress and to explain the dimensional impact of mental disorders on the organism, not only on the brain but on other organs of the body. Moreover, it is also suitable to explain the neuroprogression of psychiatric disorders from a ‘wear and tear’ approach, detailing the progressive increase of cognitive impairment, accelerated ageing, and rates of medical and psychiatric comorbidities that patients with major psychiatric disorders have. In this chapter, the concepts of allostasis, allostatic load, and allostatic overload are detailed from a neuroprogressive approach and their application to neuropsychiatric illnesses is explained in relation to anxiety disorders, affective disorders, such as unipolar depression and bipolar disorder, and psychotic syndromes.

scholarly journals Life Course Predictors of Allostatic Load Among LGBTQ Older Adults

2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 735-735
Author(s):  
Charles Hoy-Ellis ◽  
Hyun Kim ◽  
Karen Fredriksen Goldsen
Keyword(s):  
Older Adults ◽  
Life Course ◽  
Interpersonal Violence ◽  
Allostatic Load ◽  
Identity Management ◽  
The Body ◽  
Linear Regression Models ◽  
Psychophysiological Stress ◽  
Increased Risk ◽  
Wear And Tear

Abstract LGBTQ older adults are at significantly increased risk for poor mental and physical health, likely consequential to lifelong bias. Allostatic load (AL), the net effect of “wear and tear” on the body resulting from repeated, chronic over-activation of the psychophysiological stress response system. Utilizing the Health Equity Promotion Model, the aim of this study was to test potential life course predictors of AL, including interpersonal violence, legal marriage, and identity management in a sample of LGBTQ adults 50 to 97 years of age (n=317). Results from a series of hierarchical linear regression models showed that adult physical abuse and late identity disclosure for those who had been in an opposite-sex marriage predicted higher AL in this sample of LGBTQ older adults, indicating need for increased research on bias over the life course as contributory to AL and biopsychosocial dysfunction among LGBTQ older adults.

Suicide Loss Survivors: Navigating Social Stigma and Threats to Social Bonds

2021 ◽  
pp. 003022282110265
Author(s):  
Dorothy M. Goulah-Pabst
Keyword(s):  
Social Stigma ◽  
Qualitative Interviews ◽  
Healing Process ◽  
Personal Narratives ◽  
The Body ◽  
Social Solidarity ◽  
Sociological Study ◽  
Social Challenges ◽  
The Social ◽  
The Impact

The complicated grief experienced by suicide loss survivors leads to feelings of abandonment, rejection, intense self-blame, and depression. Stigma surrounding suicide further burdens survivors who can experience rejection by their community and social networks. Research in the field of psychology has delved into the grieving process of suicide loss survivors, however the effects of suicide require more sociological study to fully understand and support the impact of the suicidal bereavement process on the social interactions and relationships of those left behind after death. This study aims to contribute to the body of research exploring the social challenges faced after the suicide of a loved one. Based on the analysis of powerful personal narratives through qualitative interviews shared by 14 suicide loss survivors this study explores the social construction of the grieving and healing process for suicide loss survivors. Recognizing that the most reliable relief is in commiseration with like experienced people, this research points to the support group as a builder of social solidarity. The alienation caused by the shame and stigma of suicide loss can be reversed by the feelings of attachment to the group that listens, understands and accepts. Groups created by and for suicide loss survivors should be considered a necessary tool to be used toward healing those who suffer from loss by suicide.

scholarly journals Gene regulation contributes to explain the impact of early life socioeconomic disadvantage on adult inflammatory levels in two cohort studies

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Cristian Carmeli ◽  
Zoltán Kutalik ◽  
Pashupati P. Mishra ◽  
Eleonora Porcu ◽  
Cyrille Delpierre ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Gene Regulation ◽  
Cohort Studies ◽  
Early Life ◽  
Life Experiences ◽  
Socioeconomic Disadvantage ◽  
Mediating Role ◽  
The Impact ◽  
The Relationship

AbstractIndividuals experiencing socioeconomic disadvantage in childhood have a higher rate of inflammation-related diseases decades later. Little is known about the mechanisms linking early life experiences to the functioning of the immune system in adulthood. To address this, we explore the relationship across social-to-biological layers of early life social exposures on levels of adulthood inflammation and the mediating role of gene regulatory mechanisms, epigenetic and transcriptomic profiling from blood, in 2,329 individuals from two European cohort studies. Consistently across both studies, we find transcriptional activity explains a substantive proportion (78% and 26%) of the estimated effect of early life disadvantaged social exposures on levels of adulthood inflammation. Furthermore, we show that mechanisms other than cis DNA methylation may regulate those transcriptional fingerprints. These results further our understanding of social-to-biological transitions by pinpointing the role of gene regulation that cannot fully be explained by differential cis DNA methylation.

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