Central role of the brain in stress and adaptation: Links to socioeconomic status, health, and disease

McEwen, Bruce S.; Gianaros, Peter J.

doi:10.1111/j.1749-6632.2009.05331.x

Cited by 1,715Stress Responses and CortisolResilience and Mental HealthHealth, psychology, and well-being

Central role of the brain in stress and adaptation: Links to socioeconomic status, health, and disease

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McEwen, Bruce S., Gianaros, Peter J.·2010·Annals of the New York Academy of Sciences

DOI 10.1111/j.1749-6632.2009.05331.xPMC PMC2864527

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Abstract

The brain is the key organ of stress reactivity, coping, and recovery processes. Within the brain, a distributed neural circuitry determines what is threatening and thus stressful to the individual. Instrumental brain systems of this circuitry include the hippocampus, amygdala, and areas of the prefrontal cortex. Together, these systems regulate physiological and behavioral stress processes, which can be adaptive in the short‐term and maladaptive in the long‐term. Importantly, such stress processes arise from bidirectional patterns of communication between the brain and the autonomic, cardiovascular, and immune systems via neural and endocrine mechanisms underpinning cognition, experience, and behavior. In one respect, these bidirectional stress mechanisms are protective in that they promote short‐term adaptation ( allostasis ). In another respect, however, these stress mechanisms can lead to a long‐term dysregulation of allostasis in that they promote maladaptive wear‐and‐tear on the body and brain under chronically stressful conditions ( allostatic load ), compromising stress resiliency and health. This review focuses specifically on the links between stress‐related processes embedded within the social environment and embodied within the brain, which is viewed as the central mediator and target of allostasis and allostatic load.

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The autonomic nervous system (ANS) and the hypothalamus-pituitary-adrenal (HPA) axis are the two main stress response systems of humans.
“The autonomic nervous system (ANS) and the hypothalamus-pituitary-adrenal axis (HPA axis) are considered the two main stress response systems of humans (9, 10).”
From Physiological attunement and flourishing: understanding the influence of relationships on health (2025) · cites this paper as [9]
The “Stress, allostasis, and allostatic load” section identifies the HPA axis and autonomic nervous system as systems involved in adaptation to stress. It also lists several other systems and does not designate the HPA axis and ANS as the two main human stress-response systems. No page number is available in our copy. (LLM, conf=0.86)
Experimental — accuracy not yet measured
Chronic stress exposure during early development has lasting effects on stress responses.
“exposure to chronic stress during early development has lasting effects on stress responses (see McEwen & Gianaros 2010 for a review)”
From Adolescent Suicide as a Failure of Acute Stress-Response Systems. (2019) · cites this paper as McEwen & Gianaros 2010
The brain plays a critical role in appraising stressors and in modulating immune system reactivity to physical and social threat.
“the brain plays a critical role in appraising stressors, as well as in modulating immune system reactivity to physical and social threat”
From From stress to inflammation and major depressive disorder: A social signal transduction theory of depression. (2014) · cites this paper as McEwen & Gianaros, 2010
Allostatic load theory holds that physiological wear and tear results from chronic activation of stress systems.
“This idea is formalized in allostatic load theory, which holds that physiological wear and tear result from chronic activation of stress systems (McEwen & Gianaros, 2010; McEwen & Stellar, 1993).”
From Strong Enough to Suffer: Emotional Suppression, Stress Exposure, and Physiological Health Among Men Across the Life Course (2026) · cites this paper as McEwen & Gianaros, 2010

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Neuronal Circuit Regulation of the Hypothalamo-Pituitary-Adrenocortical Stress Axis
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Reversible paired helical filament-like phosphorylation of tau is an adaptive process associated with neuronal plasticity in hibernating animals
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Interleukin-6 Covaries Inversely with Hippocampal Grey Matter Volume in Middle-Aged Adults
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Cardiovascular reactivity in cardiovascular disease: “Once more unto the breach”
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Self-esteem, locus of control, hippocampal volume, and cortisol regulation in young and old adulthood
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Mild, Short-term Stress Alters Dendritic Morphology in Rat Medial Prefrontal Cortex
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Objective and subjective socioeconomic status and susceptibility to the common cold.
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Chronic 'jet lag' produces temporal lobe atrophy and spatial cognitive deficits
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Transgenic brain-derived neurotrophic factor expression causes both anxiogenic and antidepressant effects
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Prospective reports of chronic life stress predict decreased grey matter volume in the hippocampus
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[76]McEwen BS Physiology and neurobiology of stress and adaptation: central role of the brain. Physiol. Rev 2007 87 873 904 17615391
[105]Kuroda Y McEwen BS Effect of chronic restraint stress and tianeptine on growth factors, GAP-43 and MAP2 mRNA expression in the rat hippocampus. Mol. Brain Res 1998 59 35 39 9729259
[195]Phillips ML Neurobiology of emotion perception II: implications for major psychiatric disorders. Biol. Psychiatry 2003 54 515 528 12946880
[269]Szeszko PR Brain-derived neurotrophic factor val66met polymorphism and volume of the hippocampal formation. Mol. Psychiat 2005 10 631 636 15768049

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“These responses are known to be adaptive and have effects that influence future HPA axis responses (McEwen & Gianaros, 2010).”
Background
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In the Eye of the Beholder: Individual Differences in Perceived Social Isolation Predict Regional Brain Activation to Social Stimuli
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The Impact of Childhood Maltreatment: A Review of Neurobiological and Genetic Factors
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The neural diathesis-stress model of schizophrenia revisited: an update on recent findings considering illness stage and neurobiological and methodological complexities
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The Lancet Psychiatry Commission on intimate partner violence and mental health: advancing mental health services, research, and policy
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Early-life stress, HPA axis adaptation, and mechanisms contributing to later health outcomes
Maniam, J., Antoniadis, C., & Morris, M. J. (2014) · Frontiers in Endocrinology · doi:10.3389/fendo.2014.00073 · Cited by 295 · see citing works
Does spending time outdoors reduce stress? A review of real-time stress response to outdoor environments
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Psychosocial aspects in cardiac rehabilitation: From theory to practice. A position paper from the Cardiac Rehabilitation Section of the European Association of Cardiovascular Prevention and Rehabilitation of the European Society of Cardiology
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Chronic Pain and Chronic Stress: Two Sides of the Same Coin?
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Racial discrimination and child and adolescent health in longitudinal studies: A systematic review
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BDNF in sleep, insomnia, and sleep deprivation
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Childhood Poverty, Cumulative Risk Exposure, and Mental Health in Emerging Adults
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Adverse childhood experiences and the onset of chronic disease in young adulthood
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A transdisciplinary perspective of chronic stress in relation to psychopathology throughout life span development
Juster, R.-P., Bizik, G., Picard, M., Arsenault-Lapierre, G., Sindi, S., Trepanier, L., Marin, M.-F., Wan, N., Sekerovic, Z., Lord, C., et al. (2011) · Development and Psychopathology · doi:10.1017/s0954579411000289 · Cited by 268 · see citing works
Self-citation
Unpacking the burden: Understanding the relationships between chronic pain and comorbidity in the general population
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MULTIPLE PATHWAYS LINKING RACISM TO HEALTH OUTCOMES
Harrell, C. J. P., Burford, T. I., Cage, B. N., Nelson, T. M., Shearon, S., Thompson, A., & Green, S. (2011) · Du Bois Review: Social Science Research on Race · doi:10.1017/s1742058x11000178 · Cited by 257 · see citing works
Associations between symptoms of depression and anxiety and cortisol responses to and recovery from acute stress
Fiksdal, A., Hanlin, L., Kuras, Y., Gianferante, D., Chen, X., Thoma, M. V., & Rohleder, N. (2019) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2018.11.035 · Cited by 258 · see citing works
Review: A systematic review of hypothalamic-pituitary-adrenal axis function in schizophrenia: implications for mortality
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Effects of Chronic Social Stress on Obesity
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Microbial ‘Old Friends’, immunoregulation and stress resilience
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Effects of poverty on interacting biological systems underlying child development
Jensen, S. K. G., Berens, A. E., & Nelson, C. A. (2017) · The Lancet Child & Adolescent Health · doi:10.1016/s2352-4642(17)30024-x · Cited by 241 · see citing works
What Reduces Sexual Minority Stress? A Review of the Intervention “Toolkit”
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Mindfulness meditation training alters stress-related amygdala resting state functional connectivity: a randomized controlled trial
Taren, A. A., Gianaros, P. J., Greco, C. M., Lindsay, E. K., Fairgrieve, A., Brown, K. W., Rosen, R. K., Ferris, J. L., Julson, E., Marsland, A. L., et al. (2015) · Social Cognitive and Affective Neuroscience · doi:10.1093/scan/nsv066 · Cited by 236 · see citing works
Self-citation
The Brain on Stress: Toward an Integrative Approach to Brain, Body, and Behavior
McEwen, B. S. (2013) · Perspectives on Psychological Science · doi:10.1177/1745691613506907 · Cited by 237 · see citing works
Self-citation
Adolescent Suicide as a Failure of Acute Stress-Response Systems.
Miller, A. B., & Prinstein, M. J. (2019) · Annual Review of Clinical Psychology · doi:10.1146/annurev-clinpsy-050718-095625 · Cited by 235 · see citing works
“Research also indicates that exposure to chronic stress during early development has lasting effects on stress responses (see McEwen & Gianaros 2010 for a review).”
Background
Burden of Environmental Adversity Associated With Psychopathology, Maturation, and Brain Behavior Parameters in Youths
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Issue: The Biology of Disadvantage Central role of the brain in stress and adaptation: Links to socioeconomic status, health, and disease
McEwen, B. S., & Gianaros, P. J. (2016)
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Central Role of the Brain in Stress and Adaptation: Allostasis, Biological Embedding, and Cumulative Change
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Authors: McEwen, B. S., & Gianaros, P. J.
Affiliations: Rockefeller University (US)
University of Pittsburgh (US)
Corresponding author: McEwen, Bruce S.
ORCID: McEwen, Bruce S.
Gianaros, Peter J.
Venue: Annals of the New York Academy of Sciences
Publisher: Wiley
Published: 2010-02
Volume: 1186
Issue: 1
Pages: 190-222
ISSN: 0077-8923 (ISSN-L)
1749-6632
DOI: 10.1111/j.1749-6632.2009.05331.x
PMC: PMC2864527
OpenAlex: W1686749590
Cited by: 1,715
References: 331
Citations by year: 2026: 99 · 2025: 117 · 2024: 91 · 2023: 101 · 2022: 135 · 2021: 120 · 2020: 138 · 2019: 109 · 2018: 98 · 2017: 117 · 2016: 102 · 2015: 111 · 2014: 100 · 2013: 89 · 2012: 95
FWCI: 7.70
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor, 15 d)
Locations: Annals of the New York Academy of Sciences (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: John D. and Catherine T. MacArthur Foundation
National Institutes of Health (MH41256, MH58911)
National Heart, Lung, and Blood Institute (R01HL089850)
National Institute of Mental Health (5P01 MH58911, K01MH070616, R01 MH41256, P50MH058911, R01MH041256)
Topics: Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
Social Sciences › Psychology › Clinical Psychology › Resilience and Mental Health
Health Sciences › Health Professions › General Health Professions › Health, psychology, and well-being
Keywords: stress, allostasis, allostatic load, socioeconomic status, stress reactivity, coping, hippocampus, amygdala, prefrontal cortex, stress resilience, neuroimmune interactions, chronic stress, health and disease, social environment
MeSH terms: Adaptation, Physiological, Amygdala, Brain, Health Status, Hippocampus, Humans, Social Class, Stress, Physiological, Allostasis

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Central role of the brain in stress and adaptation: Links to socioeconomic status, health, and disease

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