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Cited by 822Stress Responses and CortisolHealth disparities and outcomesBirth, Development, and Health

Low early-life social class leaves a biological residue manifested by decreased glucocorticoid and increased proinflammatory signaling

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Miller, Gregory E., Chen, Edith, Fok, Alexandra K., Walker, Hope, Lim, Alvin, Nicholls, Erin F., Cole, Steve, Kobor, Michael S.·2009·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.0902971106PMC PMC2732821
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Abstract

Children reared in unfavorable socioeconomic circumstances show increased susceptibility to the chronic diseases of aging when they reach the fifth and sixth decades of life. One mechanistic hypothesis for this phenomenon suggests that social adversity in early life programs biological systems in a manner that persists across decades and thereby accentuates vulnerability to disease. Here we examine the basic tenets of this hypothesis by performing genome-wide transcriptional profiling in healthy adults who were either low or high in socioeconomic status (SES) in early life. Among subjects with low early-life SES, there was significant up-regulation of genes bearing response elements for the CREB/ATF family of transcription factors that conveys adrenergic signals to leukocytes, and significant down-regulation of genes with response elements for the glucocorticoid receptor, which regulates the secretion of cortisol and transduces its antiinflammatory actions in the immune system. Subjects from low-SES backgrounds also showed increased output of cortisol in daily life, heightened expression of transcripts bearing response elements for NF-κB, and greater stimulated production of the proinflammatory cytokine interleukin 6. These disparities were independent of subjects' current SES, lifestyle practices, and perceived stress. Collectively, these data suggest that low early-life SES programs a defensive phenotype characterized by resistance to glucocorticoid signaling, which in turn facilitates exaggerated adrenocortical and inflammatory responses. Although these response patterns could serve adaptive functions during acute threats to well-being, over the long term they might exact an allostatic toll on the body that ultimately contributes to the chronic diseases of aging.

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  • Other kinds of childhood adversity, such as low socioeconomic status, have been linked to low-grade inflammation in adulthood, as well as mental and physical health problems across the lifespan.

    “Previous research in this area has focused on maltreatment, but other kinds of childhood adversity, such as low socioeconomic status (SES), have been linked to low-grade inflammation in adulthood (18–20), as well as mental and physical health problems across the lifespan (21).”

    From Clustering of depression and inflammation in adolescents previously exposed to childhood adversity (2012) · cites this paper as [18]

  • Elevated proinflammatory cytokine has been reported in the cerebrospinal fluid of clinically depressed patients.

    “In support of this, elevated proinflammatory cytokine has been reported in the cerebrospinal fluid of clinically depressed patients (Levine et al, 1999;Miller et al, 2009).”

    From Repeated Social Defeat, Neuroinflammation, and Behavior: Monocytes Carry the Signal (2017) · cites this paper as Miller et al, 2009

  • The GR-insensitive monocytes were primed to immune activation, as they produced elevated IL-6 following immune stimulation ex vivo.

    “Furthermore, the GR-insensitive monocytes were primed to immune activation, as they produced elevated IL-6 following immune stimulation ex vivo (Miller et al, 2009).”

    From Repeated Social Defeat, Neuroinflammation, and Behavior: Monocytes Carry the Signal (2017) · cites this paper as Miller et al, 2009

  • Circulating monocytes from healthy adult subjects (25-40 years old) raised in unfavorable socioeconomic circumstances had decreased transcriptional activity of GR and increased transcriptional activity of NF-κB.

    “For example, circulating monocytes from healthy adult subjects (25-40 years old) raised in unfavorable socioeconomic circumstances had decreased transcriptional activity of GR and increased transcriptional activity of NF-κB.”

    From Repeated Social Defeat, Neuroinflammation, and Behavior: Monocytes Carry the Signal (2017) · cites this paper as Miller et al, 2009

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Research works printed but not linked: 3

  1. [13]Coe CL, Lubach GR. In: Psychoneuroimmunology. 4th Ed. Ader R, editor. Boston: Elsevier; 2007. pp. 455–474. [Google Scholar]
  2. [34]Office of National Statistics. The National Statistics Socio-Economic Classification. Hampshire, UK: Palgrave Macmillan; 2005. [Google Scholar]
  3. [37]Miller RG. Beyond ANOVA. New York: Wiley; 1986. [Google Scholar]

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Authors
Miller, G. E., Chen, E., Fok, A. K., Walker, H., Lim, A., Nicholls, E. F., Cole, S., & Kobor, M. S.
Affiliations
  • University of British Columbia (CA)
  • University of California, Los Angeles (US)
ORCID
Venue
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences
Published
2009-08-25
Volume
106
Issue
34
Pages
14716-14721
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
DOI
10.1073/pnas.0902971106
PMC
PMC2732821
OpenAlex
W2099390922
Cited by
822
References
42
Citations by year
2026: 31 · 2025: 33 · 2024: 38 · 2023: 34 · 2022: 42 · 2021: 37 · 2020: 44 · 2019: 50 · 2018: 57 · 2017: 61 · 2016: 73 · 2015: 69 · 2014: 52 · 2013: 59 · 2012: 61
FWCI
17.78
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Heart and Stroke Foundation of Canada
  • Canadian Institute for Advanced Research
  • Michael Smith Health Research BC
  • National Institute of Child Health and Human Development
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD0058502, R01HD058502)
Topics
  • Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
  • Social Sciences › Health › Health disparities and outcomes
  • Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Birth, Development, and Health
Keywords
childhood socioeconomic status, social adversity, glucocorticoid resistance, glucocorticoid receptor, NF-κB, interleukin-6, pro-inflammatory signaling, cortisol, adrenocortical response, allostatic load, gene expression profiling, leukocytes
MeSH terms
Adult, British Columbia, Cells, Cultured, Enzyme-Linked Immunosorbent Assay, Female, Glucocorticoids, Humans, Hydrocortisone, Immunoassay, Leukocytes, Mononuclear, Male, Promoter Regions, Genetic, Receptors, Glucocorticoid, Social Class, Socioeconomic Factors, Signal Transduction, Interleukin-6, NF-kappa B, Reverse Transcriptase Polymerase Chain Reaction, Response Elements, Oligonucleotide Array Sequence Analysis, Gene Expression Profiling

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