Immune and Epigenetic Pathways Linking Childhood Adversity and Health Across the Lifespan
Michelle A. ChenAngie S. LeRoyMarzieh MajdJonathan Y. ChenRyan L. BrownLisa M. ChristianChristopher P. Fagundes
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Abstract:
Childhood adversity is associated with a host of mental and physical health problems across the lifespan. Individuals who have experienced childhood adversity (e.g., child abuse and neglect, family conflict, poor parent/child relationships, low socioeconomic status or extreme poverty) are at a greater risk for morbidity and premature mortality than those not exposed to childhood adversity. Several mechanisms likely contribute to the relationship between childhood adversity and health across the lifespan (e.g., health behaviors, cardiovascular reactivity). In this paper, we review a large body of research within the field of psychoneuroimmunology, demonstrating the relationship between early life stress and alterations of the immune system. We first review the literature demonstrating that childhood adversity is associated with immune dysregulation across different indices, including proinflammatory cytokine production (and its impact on telomere length), illness and infection susceptibility, latent herpesvirus reactivation, and immune response to a tumor. We then summarize the growing literature on how childhood adversity may alter epigenetic processes. Finally, we propose future directions related to this work that have basic and applied implications.Keywords:
Allostatic load
Psychoneuroimmunology
This study aimed to determine if Alzheimer caregivers have increased allostatic load compared to non-caregivers. Potential psychological moderators (mastery, depression, and role overload) of the relationship between caregiving status and allostatic load were also explored. Eighty-seven caregivers and 43 non-caregivers underwent biological assessment of allostatic load and psychological assessments. Caregivers had significantly higher allostatic load compared to non-caregivers ( p < .05). Mastery, but not depression or overload, moderated the relationship between caregiving status and allostatic load. In conclusion, allostatic load may represent a link explaining how stress translates to downstream pathology, but more work is necessary to understand the role of psychological factors.
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To elucidate the historical development of the allostatic load concept, alongside its use in nursing research, and to explore how allostatic load has been investigated among two stress-vulnerable populations.'Stress' is a prominent term in understanding the development of disease. Allostatic load is among several approaches undertaken to quantify the magnitude of stress and understand how stress can affect health.We explored the advent of allostatic load including its antecedents, and consequences. We used an exemplar case to apply the concept. We reviewed studies that used allostatic load among workers and women of childbearing age.There remains a need to consolidate a common definition and operationalisation of allostatic load. Despite this need for further work, allostatic load is a good fit for nursing science which focuses on the client, environment and health. Only 12 studies explored allostatic load among workers (n = 6) and women of childbearing age (n = 6). In some studies, allostatic load was used as a predictor while in others it was used as an outcome. None of the studies considered it as a mediator.The concept of allostatic load holds promise for nursing researchers to operationalise a holistic view of multiple stressors and to quantify their effects on health. Studies are needed to affirm the role of allostatic load as a potential mediator between multiple stressors and outcomes. Longitudinal studies are also needed to demonstrate a causal pathway from stressor exposure to tertiary outcomes such as chronic conditions and morbidity.Allostatic load is a useful concept for nurses working with stress-vulnerable populations. With the use of an interpretable allostatic load index, nurses will be able to intervene at various stages of the allostasis-adaptation process (stress-response) and adjust interventions accordingly.
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Abstract Objective This study explores how status and processes of cumulative dis/advantage shape allostatic load across the life course. Methods Data from these analyses are from a national sample of adults from the Biomarker Substudy of the Study of Midlife in the US (MIDUS), a longitudinal study of health and well-being in the United States (N=1186) aged 35-86 years old. Education level, multiple indicators of financial stability, and demographic data were used to construct a measure of status. Those in the Biomarker substudy completed a physiological assessment that included blood, urine, and saliva assays to assess functioning of the sympathetic and parasympathetic nervous systems, hypothalamic-pituitary-adrenal axis, cardiovascular, inflammatory immune activity, glucose metabolic system, and lipid metabolic system. These data were used to create an allostatic load index. An alternate allostatic load index was developed using reported medication to affect three of seven biological systems: cardiovascular and the glucose and lipid metabolic systems. Nested regression models were estimated to explain differences in allostatic load. Results Reported financial instability across the life course was associated with higher levels of allostatic load, and higher levels of education were associated with lower levels of allostatic load, both with and without reported medication usage. Conclusion These findings demonstrate that structural forces impact allostatic load, both with and without reported medication usage, and expand previous work on allostatic load and social status.
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Allostatic load
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Allostatic load provides a useful framework for conceptualizing the multisystem physiological impact of sustained stress and its effects on health and well-being. Research across two decades shows that allostatic load indices predict health outcomes including all-cause mortality and vary with stress and related psychosocial constructs. The study by Slopen and colleagues in this issue provides an example both of the utility of the allostatic load framework and of limitations in related literature, such as inconsistencies in conceptualization and measurement across studies, and the frequent application of cross-sectional designs. The current article describes these limitations and provides suggestions for further research to enhance the value and utility of the allostatic load framework in biobehavioral medicine research.
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Psychoneuroimmunology
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Allostatic load is a sub-clinical dysregulation state, resulting from the body’s response to stress. Allostatic load accumulates gradually over the life course and affects a number of physiological systems. Measuring multisystem dysregulation , and changes in it over time, is very challenging. In this paper, we discuss composite measures used to capture allostatic load and the challenges involved in deriving and using these measures. Our focus is on measuring allostatic load in later life.
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The stress pathway posits that those in disadvantaged circumstances are exposed to a higher degree of stressful experiences over time resulting in an accumulated biological burden which subsequently relates to poorer health. Trajectories of disadvantage, in the form of neighbourhood deprivation and structural social capital, are evaluated in their relation to allostatic load representing the cumulative “wear and tear” of chronic stress. This paper uses data from the British Household Panel Survey and Understanding Society in a latent class growth analysis. We identify groups of exposure trajectories over time using these classes to predict allostatic load at the final wave. The results show that persistent exposure to higher deprivation is related to worse allostatic load. High structural social capital over time relates to lower allostatic load, in line with a stress buffering effect, though this relationship is not robust to controlling for individual sociodemographic characteristics. By demonstrating a gradient in allostatic load by histories of deprivation, this analysis supports a biological embedding of disadvantage through chronic exposure to stressful environments as an explanation for social health inequalities.
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Abstract In the last decades, psychoneuroendocrineimmunology research has made relevant contributions to the fields of neuroscience, psychobiology, epigenetics, molecular biology, and clinical research by studying the effect of stress on human health and highlighting the close interrelations between psyche, brain, and bodily systems. It is now well recognized that chronic stress can alter the physiological cross‐talk between brain and biological systems, leading to long‐lasting maladaptive effects (allostatic overload) on the nervous, immune, endocrine, and metabolic systems, which compromises stress resiliency and health. Stressful conditions in early life have been associated with profound alterations in cortical and subcortical brain regions involved in emotion regulation and the salience network, showing relevant overlap with different psychiatric conditions. This paper provides a summary of the available literature concerning the notable effects of stress on the brain and immune system. We highlight the role of epigenetics as a mechanistic pathway mediating the influences of the social and physical environment on brain structure and connectivity, the immune system, and psycho‐physical health in psychiatric diseases. We also summarize the evidence regarding the effects of stress management techniques (mainly psychotherapy and meditation practice) on clinical outcomes, brain neurocircuitry, and immune‐inflammatory network in major psychiatric diseases.
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