The DOI matches its Crossref record; 41 of the 42 references it cites were found in a registry or an index.
Low early-life social class leaves a biological residue manifested by decreased glucocorticoid and increased proinflammatory signaling
Open accessAbstract
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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“The result is continuous transcription and release of proinflammatory cytokines, while repressing transcription factors associated with interferon responses and antiviral action (Cole, 2019; Miller et al., 2008; Miller et al., 2009).”
From On race, human variation, and who gets and dies of sepsis (2022) · cites this paper as Miller et al., 2009
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“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]
In the citing paper
“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
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“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
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“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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“Much like fight-or-f light, this pattern of exaggerated responding could serve adaptive functions in the context of acute threats to well-being, but if activated chronically may exact an allostatic toll on the body that ultimately contributes to the chronic diseases of aging (22, 23).”
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- The National Statistics Socio-Economic Classification (Palgrave Macmillan, Hampshire, UK, 2005).
- RG Miller Beyond ANOVA (Wiley, New York, 1986).
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Metadata
- 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)
- 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
- 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
- green
- www.ncbi.nlm.nih.gov
- 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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