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.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“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
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“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
In the citing paper
“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
In the citing paper
“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
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
The Pittsburgh Sleep Quality Index: a new instrument for psychiatric practice and research
Buysse, D. J., Reynolds, C. F., Monk, T. H., Berman, S. R., & Kupfer, D. J. (1989) · Psychiatry Research · doi:10.1016/0165-1781(89)90047-4 · Cited by 35,234
A Global Measure of Perceived Stress
Cohen, S., Kamarck, T., & Mermelstein, R. (1983) · Journal of Health and Social Behavior · doi:10.2307/2136404 · Cited by 32,807
Child abuse: Adolescent records vs. adult recall
Femina, D. D., Yeager, C. A., & Lewis, D. O. (1990) · Child Abuse & Neglect · doi:10.1016/0145-2134(90)90033-p · Cited by 8,820
Protective and Damaging Effects of Stress Mediators
McEwen, B. S. (1998) · New England Journal of Medicine · doi:10.1056/nejm199801153380307 · Cited by 6,733 · cited 1×
“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).”
BackgroundEffect of In Utero and Early-Life Conditions on Adult Health and Disease
Gluckman, P. D., Hanson, M. A., Cooper, C., & Thornburg, K. L. (2008) · New England Journal of Medicine · doi:10.1056/nejmra0708473 · Cited by 3,898
Psychological Stress and Disease
Cohen, S., Janicki-Deverts, D., & Miller, G. E. (2007) · JAMA · doi:10.1001/jama.298.14.1685 · Cited by 3,168
Self-citationMeaney, M. J. (2001) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.24.1.1161 · Cited by 2,708
Heim, C. (2000) · JAMA · doi:10.1001/jama.284.5.592 · Cited by 1,968
Childhood maltreatment predicts adult inflammation in a life-course study
Danese, A., Pariante, C. M., Caspi, A., Taylor, A., & Poulton, R. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0610362104 · Cited by 1,264
Meaney, M. J., & Szyf, M. (2005) · Dialogues in Clinical Neuroscience · doi:10.31887/dcns.2005.7.2/mmeaney · Cited by 958
Neuroendocrine Regulation of Immunity
Webster, J. I., Tonelli, L., & Sternberg, E. M. (2002) · Annual Review of Immunology · doi:10.1146/annurev.immunol.20.082401.104914 · Cited by 957
GUNNAR, M. R., & VAZQUEZ, D. M. (2001) · Development and Psychopathology · doi:10.1017/s0954579401003066 · Cited by 900
Pace, T. W. W., Mletzko, T. C., Alagbe, O., Musselman, D. L., Nemeroff, C. B., Miller, A. H., & Heim, C. M. (2006) · American Journal of Psychiatry · doi:10.1176/ajp.2006.163.9.1630 · Cited by 810
Miller, G. E., Cohen, S., & Ritchey, A. K. (2002) · Health Psychology · doi:10.1037/0278-6133.21.6.531 · Cited by 769
Self-citationGalobardes, B. (2004) · Epidemiologic Reviews · doi:10.1093/epirev/mxh008 · Cited by 753
Heim, C., Newport, D. J., Bonsall, R., Miller, A. H., & Nemeroff, C. B. (2001) · American Journal of Psychiatry · doi:10.1176/appi.ajp.158.4.575 · Cited by 746
Social regulation of gene expression in human leukocytes
Cole, S. W., Hawkley, L. C., Arevalo, J. M., Sung, C. Y., Rose, R. M., & Cacioppo, J. T. (2007) · Genome Biology · doi:10.1186/gb-2007-8-9-r189 · Cited by 745
Self-citationPerkins, N. D. (2006) · Oncogene · doi:10.1038/sj.onc.1209937 · Cited by 674
Galobardes, B., Smith, G. D., & Lynch, J. W. (2006) · Annals of Epidemiology · doi:10.1016/j.annepidem.2005.06.053 · Cited by 643
The biological embedding of early experience and its effects on health in adulthood
HERTZMAN, C. (1999) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1999.tb08107.x · Cited by 631
Pace, T. W. W., Hu, F., & Miller, A. H. (2007) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2006.08.009 · Cited by 621
Developmental determinants of sensitivity and resistance to stress
Levine, S. (2005) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2005.03.013 · Cited by 574
Miller, G. E., Chen, E., Sze, J., Marin, T., Arevalo, J. M. G., Doll, R., Ma, R., & Cole, S. W. (2008) · Biological Psychiatry · doi:10.1016/j.biopsych.2008.03.017 · Cited by 552
Self-citationMeasurement of physical activity to assess health effects in free-living populations
Paffenbarger, R. S., Blair, S. N., Lee, I.-M. M., & Hyde, R. T. (1993) · Medicine & Science in Sports & Exercise · doi:10.1249/00005768-199301000-00010 · Cited by 523
Maternal programming of steroid receptor expression and phenotype through DNA methylation in the rat
Szyf, M., Weaver, I. C. G., Champagne, F. A., Diorio, J., & Meaney, M. J. (2005) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2005.10.002 · Cited by 348
Taylor, S. E., Lehman, B. J., Kiefe, C. I., & Seeman, T. E. (2006) · Biological Psychiatry · doi:10.1016/j.biopsych.2006.03.016 · Cited by 296
Social stress induces glucocorticoid resistance in macrophages
Stark, J. L., Avitsur, R., Padgett, D. A., Campbell, K. A., Beck, F. M., & Sheridan, J. F. (2001) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.2001.280.6.r1799 · Cited by 295
Parental Depression: Animal Models of an Adverse Life Event
Newport, D. J., Stowe, Z. N., & Nemeroff, C. B. (2002) · American Journal of Psychiatry · doi:10.1176/appi.ajp.159.8.1265 · Cited by 269
GSMN-TB: a web-based genome-scale network model of Mycobacterium tuberculosismetabolism
Beste, D. J. V., Hooper, T., Stewart, G. R., Bonde, B. K., Avignone-Rossa, C. A., Bushell, M. E., Wheeler, P. R., Klamt, S., Kierzek, A. M., & McFadden, J. (2007) · Genome biology · doi:10.1186/gb-2007-8-5-r89 · Cited by 207
Maternal programming of defensive responses through sustained effects on gene expression
Zhang, T.-Y., Bagot, R., Parent, C., Nesbitt, C., Bredy, T. W., Caldji, C., Fish, E., Anisman, H., Szyf, M., & Meaney, M. J. (2006) · Biological Psychology · doi:10.1016/j.biopsycho.2006.01.009 · Cited by 206
Developmental Origins of Health and Disease
Rass, E. (2017) · Routledge eBooks · doi:10.4324/9781315445564-6 · Cited by 200
Childhood Socioeconomic Status and Host Resistance to Infectious Illness in Adulthood
Cohen, S., Doyle, W. J., Turner, R. B., Alper, C. M., & Skoner, D. P. (2004) · Psychosomatic Medicine · doi:10.1097/01.psy.0000126200.05189.d3 · Cited by 187
Expression-based monitoring of transcription factor activity: the TELiS database
Cole, S. W., Yan, W., Galic, Z., Arevalo, J., & Zack, J. A. (2005) · Bioinformatics · doi:10.1093/bioinformatics/bti038 · Cited by 185
Self-citationMiller, G., & Chen, E. (2007) · Psychosomatic Medicine · doi:10.1097/psy.0b013e318068fcf9 · Cited by 159
Self-citationAssociation of Childhood Socioeconomic Status With Subsequent Coronary Heart Disease in Physicians
Kittleson, M. M. (2006) · Archives of Internal Medicine · doi:10.1001/archinte.166.21.2356 · Cited by 131
Role of early stress in the individual differences in host response to viral infection
Avitsur, R., Hunzeker, J., & Sheridan, J. F. (2005) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2005.09.006 · Cited by 115
Life-time socio-economic position and cortisol patterns in mid-life
Li, L., Power, C., Kelly, S., Kirschbaum, C., & Hertzman, C. (2007) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2007.05.014 · Cited by 109
Controlling false-negative errors in microarray differential expression analysis: a PRIM approach
Cole, S. W., Galić, Z., & Zack, J. A. (2003) · Bioinformatics · doi:10.1093/bioinformatics/btg242 · Cited by 109
Self-citationThe conceptual basis for the developmental origins of health and disease
Gluckman, P. D., & Hanson, M. A. (2006) · Cambridge University Press eBooks · doi:10.1017/cbo9780511544699.004 · Cited by 54
Hirschfeld, A. F., Bettinger, J. A., Victor, R. E., Davidson, D. J., Currie, A. J., Ansermino, J. M., Scheifele, D. W., Orange, J. S., & Turvey, S. E. (2006) · Clinical Immunology · doi:10.1016/j.clim.2006.10.012 · Cited by 31
Mother-infant Interactions and the Development of Immunity from Conception through Weaning
Coe, C. L., & Lubach, G. R. (2007) · Elsevier eBooks · doi:10.1016/b978-012088576-3/50027-7 · Cited by 18
Research works printed but not linked: 2
- The National Statistics Socio-Economic Classification (Palgrave Macmillan, Hampshire, UK, 2005).
- RG Miller Beyond ANOVA (Wiley, New York, 1986).
Cited by
Sorted by citations
The social determinants of health: It’s time to consider the causes of the causes
Braveman, P., & Gottlieb, L. (2014) · Public Health Reports® · doi:10.1177/00333549141291s206 · Cited by 3,861
Slavich, G. M., & Irwin, M. R. (2014) · Psychological Bulletin · doi:10.1037/a0035302 · Cited by 2,206
Adverse childhood experiences, allostasis, allostatic load and age-related disease
Danese, A., & McEwen, B. S. (2012) · Physiology & Behavior · doi:10.1016/j.physbeh.2011.08.019 · Cited by 2,140
Miller, G. E., Chen, E., & Parker, K. J. (2011) · Psychological Bulletin · doi:10.1037/a0024768 · Cited by 1,785
Self-citationHavranek, E. P., Mujahid, M. S., Barr, D. A., Blair, I. V., Cohen, M. S., Cruz-Flores, S., Davey-Smith, G., Dennison-Himmelfarb, C. R., Lauer, M. S., Lockwood, D. W., et al. (2015) · Circulation · doi:10.1161/cir.0000000000000228 · Cited by 1,472
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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
