Review
Allostatic load biomarkers of chronic stress and impact on health and cognition

https://doi.org/10.1016/j.neubiorev.2009.10.002Get rights and content

Abstract

The allostatic load model expands the stress-disease literature by proposing a temporal cascade of multi-systemic physiological dysregulations that contribute to disease trajectories. By incorporating an allostatic load index representing neuroendocrine, immune, metabolic, and cardiovascular system functioning, numerous studies have demonstrated greater prediction of morbidity and mortality over and beyond traditional detection methods employed in biomedical practice. This article reviews theoretical and empirical work using the allostatic load model vis-à-vis the effects of chronic stress on physical and mental health. Specific risk and protective factors associated with increased allostatic load are elucidated and policies for promoting successful aging are proposed.

Introduction

Chronic psychosocial stress and consequent physiological dysregulations are increasingly viewed as catalysts of accelerated aging and agitators of disease trajectories. Individual differences in the brain's interpretations of and the body's reactions to environmental stressors are nevertheless the ultimate determinants of either vulnerability towards or resilience against stress-related diseases (Lupien et al., 2009, McEwen, 1998b, McEwen, 2009). Health and successful aging can therefore be conceptualized as one's ability to adapt and effectively respond to the dynamic challenges of being alive. Embodying this notion is the allostatic load model, which assesses physiological dysregulations that ensue when normal homeostatic functioning is shifted towards abnormal ranges via the prolonged secretion of stress hormones and the subsequent mal-adaptations this strain exerts on interdependent systems. This review summarizes theoretical developments and studies that incorporate allostatic load algorithms used to predict health and cognitive outcomes throughout lifespan development.

Section snippets

Concept of allostasis

The term allostasis refers to the process whereby an organism maintains physiological stability by changing parameters of its internal milieu by matching them appropriately to environmental demands (Sterling and Eyer, 1988). Traditional homeostatic models define health as a state in which all physiological parameters operate within normal values, while those that do not warrant pharmaceutical intervention. In contrast, allostasis defines health as a state of responsiveness and optimal

Allostatic load model

Allostatic load (AL) represents the ‘wear and tear’ the body experiences when repeated allostatic responses are activated during stressful situations (McEwen and Stellar, 1993). Real or interpreted threats to homeostasis initiate the sympathetic–adrenal–medullary (SAM) axis release of catecholamines and the hypothalamic–pituitary–adrenal (HPA) axis secretion of glucocorticoids that mobilize energy necessary for fight-or-flight responses (Sapolsky et al., 2000). Coordination of allostasis

Older and middle-aged adults

The following sections summarize studies using composite measures of AL in relation to health and cognitive outcomes throughout the lifespan (see Table 1). The MacArthur Studies of Successful Aging have provided the first steps towards an operational definition of AL. A count-based AL index representing the following 10 biomarkers was included in preliminary validation: 12-h urinary cortisol, epinephrine, and norepinephrine output; serum dehydroepiandrosterone-sulphate (DHEA-S), total

Conclusion

Decomposing which protective factors render individuals resilient to age-related health and cognitive declines depends on our conceptual definitions of successful aging and appreciation of individual differences (Lupien and Wan, 2004). Rather than being the absence of pathology or deceleration of senescence, resilience is a state of adaptation to a lifetime of stress and strain. Evidence from AL studies have clearly demonstrated that mal-adapting to stressful environments has serious

References (137)

  • F. Kapczinski et al.

    Allostatic load in bipolar disorder: implications for pathophysiology and treatment

    Neurosci. Biobehav. Rev.

    (2008)
  • A.S. Karlamangla et al.

    Increase in epinephrine excretion is associated with cognitive decline in elderly men: MacArthur studies of successful aging

    Psychoneuroendocrinology

    (2005)
  • A.S. Karlamangla et al.

    Allostatic load as a predictor of functional decline: MacArthur studies of successful aging

    J. Clin. Epidemiol.

    (2002)
  • G.F. Koob et al.

    Neurobiological mechanisms in the transition from drug use to drug dependence

    Neurosci. Biobehav. Rev.

    (2004)
  • G.F. Koob et al.

    Drug addiction, dysregulation of reward, and allostasis

    Neuropsychopharmacology

    (2001)
  • S.M. Korte et al.

    The Darwinian concept of stress: benefits of allostasis and costs of allostatic load and the trade-offs in health and disease

    Neurosci. Biobehav. Rev.

    (2005)
  • T.W. McDade

    Challenges and opportunities for integrative health research in the context of culture: a commentary on Gersten

    Soc. Sci. Med.

    (2008)
  • B.S. McEwen

    Allostasis and allostatic load: implications for neuropsychopharmacology

    Neuropsychopharmacology

    (2000)
  • B.S. McEwen

    The neurobiology of stress: from serendipity to clinical relevance

    Brain Res.

    (2000)
  • B.S. McEwen

    The neurobiology and neuroendocrinology of stress. Implications for post-traumatic stress disorder from a basic science perspective

    Psychiatr. Clin. North Am.

    (2002)
  • B.S. McEwen

    Interacting mediators of allostasis and allostatic load: towards an understanding of resilience in aging

    Metabolism

    (2003)
  • B.S. McEwen

    Mood disorders and allostatic load

    Biol. Psychiatry

    (2003)
  • B.S. McEwen

    Protection and damage from acute and chronic stress: allostasis and allostatic overload and relevance to the pathophysiology of psychiatric disorders

    Ann. N. Y. Acad. Sci.

    (2004)
  • B.S. McEwen

    Glucocorticoids, depression, and mood disorders: structural remodeling in the brain

    Metabolism

    (2005)
  • B.S. McEwen

    Sleep deprivation as a neurobiologic and physiologic stressor: Allostasis and allostatic load

    Metabolism

    (2006)
  • B.S. McEwen

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

    Eur. J. Pharmacol.

    (2008)
  • B.S. McEwen

    The brain is the central organ of stress and adaptation

    Neuroimage

    (2009)
  • S.S. Merkin et al.

    Neighborhoods and cumulative biological risk profiles by race/ethnicity in a national sample of U.S. adults: NHANES III

    Ann. Epidemiol.

    (2009)
  • M. Oresic et al.

    Lipidomics: a new window to biomedical frontiers

    Trends Biotechnol.

    (2008)
  • R. Rosmond

    Role of stress in the pathogenesis of the metabolic syndrome

    Psychoneuroendocrinology

    (2005)
  • P. Schnorpfeil et al.

    Allostatic load and work conditions

    Soc. Sci. Med.

    (2003)
  • J. Schulkin

    Allostasis: a neural behavioral perspective

    Horm. Behav.

    (2003)
  • M.S. Aldenderfer et al.

    Cluster Analysis

    (1991)
  • S. Bellingrath et al.

    Chronic work stress and exhaustion is associated with higher allostastic load in female school teachers

    Stress

    (2009)
  • L. Breiman et al.

    Classification and Regression Trees

    (1984)
  • U. Bronfenbrenner

    Toward an experimental ecology of human development

    Am. Psychol.

    (1977)
  • U. Bronfenbrenner

    Ecological models of human development

    (1994)
  • U. Bronfenbrenner

    Developmental ecology through space and time: a future perspective

  • G.P. Chrousos

    The role of stress and the hypothalamic–pituitary–adrenal axis in the pathogenesis of the metabolic syndrome: neuro-endocrine and target tissue-related causes

    Int. J. Obes.

    (2000)
  • M.S. Clark et al.

    Environmental stress, psychological stress and allostatic load

    Psychol. Health Med.

    (2007)
  • D.E. Crews

    Composite estimates of physiological stress, age, and diabetes in American Samoans

    Am J Phys Anthropol

    (2007)
  • E.M. Crimmins et al.

    Hispanic paradox in biological risk profiles

    Am. J. Public Health

    (2007)
  • E.M. Crimmins et al.

    Poverty and biological risk: the earlier “aging” of the poor

    J. Gerontol. A. Biol. Sci. Med. Sci.

    (2009)
  • J.B. Dowd et al.

    Do biomarkers of stress mediate the relation between socioeconomic status and health?

    J. Epidemiol. Community Health

    (2006)
  • J.B. Dowd et al.

    Socio-economic status, cortisol and allostatic load: a review of the literature

    Int J Epidemiol

    (2009)
  • J.W. Elias et al.

    Developing context and background underlying cognitive intervention/training studies in older populations

    J. Gerentol.

    (2007)
  • E.S. Epel

    Psychological and metabolic stress: a recipe for accelerated cellular aging?

    Hormones (Athens)

    (2009)
  • G.W. Evans

    A multimethodological analysis of cumulative risk and allostatic load among rural children

    Dev. Psychol.

    (2003)
  • G.W. Evans et al.

    Cumulative risk, maternal responsiveness, and allostatic load among young adolescents

    Dev. Psychol.

    (2007)
  • G.W. Evans et al.

    Childhood poverty, chronic stress, and adult working memory

    Proc. Natl. Acad. Sci. U.S.A.

    (2009)
  • Cited by (0)

    View full text