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Cited by 1,785Stress Responses and CortisolChild Abuse and TraumaBirth, Development, and Health

The DOI matches its Crossref record; 376 of the 376 references it cites were found in a registry or an index; none of the 470 sources its claims cite is checked for support yet.

Psychological stress in childhood and susceptibility to the chronic diseases of aging: Moving toward a model of behavioral and biological mechanisms.

Open access
Miller, Gregory E., Chen, Edith, Parker, Karen J.·2011·Psychological Bulletin
DOI 10.1037/a0024768PMC PMC3202072
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Abstract

Among people exposed to major psychological stressors in early life, there are elevated rates of morbidity and mortality from chronic diseases of aging. The most compelling data come from studies of children raised in poverty or maltreated by their parents, who show heightened vulnerability to vascular disease, autoimmune disorders, and premature mortality. These findings raise challenging theoretical questions. How does childhood stress get under the skin, at the molecular level, to affect risk for later diseases? And how does it incubate there, giving rise to diseases several decades later? Here we present a biological embedding model, which attempts to address these questions by synthesizing knowledge across several behavioral and biomedical literatures. This model maintains that childhood stress gets "programmed" into macrophages through epigenetic markings, posttranslational modifications, and tissue remodeling. As a consequence these cells are endowed with proinflammatory tendencies, manifest in exaggerated cytokine responses to challenge and decreased sensitivity to inhibitory hormonal signals. The model goes on to propose that over the life course, these proinflammatory tendencies are exacerbated by behavioral proclivities and hormonal dysregulation, themselves the products of exposure to early stress. Behaviorally, the model posits that childhood stress gives rise to excessive threat vigilance, mistrust of others, poor social relationships, impaired self-regulation, and unhealthy lifestyle choices. Hormonally, early stress confers altered patterns of endocrine and autonomic discharge. This milieu amplifies the proinflammatory environment already instantiated by macrophages. Acting in concert with other exposures and genetic liabilities, the resulting inflammation drives forward pathogenic mechanisms that ultimately foster chronic disease.

Overview

Integrity signals

Registry

Crossref · 10.1037/a0024768

Cites

376 of 376 references verified0 citation errors · 0 not checkable

Statistics

2 tests recomputed · 0 with the reported and recomputed p on opposite sides of .05

Verification

Claims the paper makes

0 of 470 cited sources checked · 0 supported · 0 flagged

  • It may state two separate claims as one. 126
  • Probably not a substantial claim. 42
  • The quote only partly states this claim. 3
158 of 158

  • The authors state this as an assumption.

    Maltreatment and socioeconomic disadvantage share enough common features to be aggregated under the rubric of chronic stress for purposes of generating a broad mechanistic model.

    “To us, these patterns suggest that it is reasonable to proceed on the assumption that maltreatment and disadvantage share enough common features that they can be aggregated under the rubric of chronic stress, at least for the purposes of generating a broad mechanistic model to guide research in this nascent area.”

  • The authors state this as an assumption.

    In the ACE premature mortality analysis, the respondent's siblings or parents were exposed to a similar household environment.

    “The assumption here was that the respondent’s siblings or parents would have been exposed to a similar household environment, so any long-term adverse health effects should be apparent in them as well.”

  • The authors state this as an assumption.

    Retrospective self-report assessments of childhood maltreatment lead to under-reporting.

    “However, the most likely scenario is that retrospective self-report assessments lead to under-reporting of maltreatment (Hardt and Rutter, 2004). Assuming this is true, the net effects would be to add noise to the data and artificially constrain variance on the maltreatment variable.”

  • The paper relies on this without support.

    The chronic diseases of aging have a reasonably well-understood pathogenesis that can be leveraged to construct a biologically plausible mechanistic model.

    “They also have a reasonably well understood pathogenesis, which can be leveraged here to construct a biologically plausible model of mechanisms through which early stress contributes to later disease.”

  • The paper relies on this without support.

    Animal models of early stress can serve as proof of principle for causal effects of early stress on later disease in humans.

    “However, studies of this nature can be done in animal models, and it is instructive to consider what they have revealed, as this evidence can serve as “proof of principle” that early stress can (or can not) causally influence later disease risk.”

  • The paper relies on this without support.

    Monocytes/macrophages play a key role in initiating and maintaining inflammation.

    “cells of the monocyte/macrophage lineage, which play a key role in initiating and maintaining inflammation”

  • The paper relies on this without support.

    Inflammation is central to a number of chronic diseases of aging.

    “a process that is central to a number of chronic diseases of aging”

  • The paper relies on this without support.

    Few Western children today reside in settings that resemble the ancestral ecology.

    “Today, few Western children reside in settings that resemble the ancestral ecology.”

  • The paper relies on this without support.

    The acute inflammatory response is essential for survival.

    “The acute inflammatory response is essential for survival - without it, minor injuries or infections would become lethal.”

  • The paper relies on this without support.

    Cortisol binds to glucocorticoid receptors in macrophages and other immune cells and slows inflammatory processes by tying up NF-kappa B.

    “cortisol binds to glucocorticoid receptors (GR’s) located within macrophages and other immune cells, and slows down the inflammatory processes. Mechanistically, this happens because the ligated GR moves into a cell’s nucleus, and ties up a protein called nuclear factor-kappa B (NF-κB)”

  • The authors state this as an assumption.

    The model assumes that early stress sets the upper and lower bounds of how monocytes and macrophages respond to challenge, rather than locking them into a fixed functional setpoint.

    “Note that the model does not suggest that monocytes/macrophages get locked into a functional setpoint from which they cannot deviate. Rather, it assigns early stress a role in setting the upper and lower bounds of how these cells will deal with challenge going forwards.”

  • The authors state this as an assumption.

    The model assumes that later experiences fine-tune monocyte and macrophage operating tendencies within the bounds set by early stress.

    “Within these programmed boundaries, later experiences are assumed to fine-tune these operating tendencies to meet more immediate demands.”

  • The authors state this as an assumption.

    Low childhood SES heightens cortisol output in a lasting manner.

    “Assuming low childhood SES does heighten cortisol output in a lasting manner, what might be the downstream consequences for inflammatory responding?”

  • The authors state this as an assumption.

    Early stress does not lock cells at a permanent setpoint; instead it calibrates how cells respond to challenge, with later experiences fine-tuning those tendencies.

    “As noted earlier, this is possible because early stress is not assumed to “lock” cells at a permanent setpoint. Rather, early stress calibrates the parameters of how cells deal with challenge going forwards, with later experiences fine-tuning these operating tendencies.”

  • The paper relies on this without support.

    Each of the five signaling molecules has a cognate receptor on or in macrophages that allows it to regulate the magnitude of inflammatory responses.

    “But more importantly, each has a cognate receptor in/on macrophages, which allows it to regulate the magnitude of these cells’ inflammatory responses to challenge.”

  • The paper relies on this without support.

    Stress can modulate the activity of cortisol, epinephrine, norepinephrine, acetylcholine, and oxytocin.

    “We focus on these molecules for two reasons, the first being that stress can modulate their activity.”

  • The authors state this as an assumption.

    Childhood disadvantage and maltreatment share enough common features to be aggregated under the rubric of chronic stress.

    “We made the assumption that these experiences shared enough common features that they could be aggregated under the rubric of chronic stress.”

  • The authors state this as an assumption.

    Heart-rate variability accurately indexes parasympathetic nervous system activity.

    “(And presuming that HRV accurately indexes PNS activity, stress affects bioavailable acetylcholine, too.)”
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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?

Statistics that don’t add up

Each reported p-value recomputed from its test statistic and degrees of freedom.

  • Inconsistent p-value: F(4,241) = 4.63, p < .001

    Minor

    The paper reports p < .001 here; recomputing from the test statistic and its degrees of freedom gives p = .001. The check cannot tell whether the statistic or the p-value is the misprint.

    Reported p < .001 · recomputed p = .001

1 of 1

Statistics recomputed

Every reported test result, recomputed from its test statistic and degrees of freedom. A result shows as not adding up only once an independent check has confirmed it.

  • Doesn’t add upF(4, 241) = 4.63reported p < .001 · recomputed p = .001

    “F(4,241) = 4.63, p < .001”

  • ConsistentF(4, 240) = 2.93reported p = .02 · recomputed p = .022

    “F(4,240) = 2.93, p = .02”

2 of 2

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Self-check results appear here once an independent check has confirmed them.

Citations

Cites

1 retracted

Flagged first, then by citations

Show all 365 references

Research works printed but not linked: 3

  1. Kohn ML 1977 Social class and conformity Chicago, IL University of Chicago Press
  2. Kop WJ Cohen N Ader R Felten D Cohen N 2001 Psychological risk factors and immune system involvement in cardiovascular disease Psychoneuroimmunology 3 525 544 New York Academic Press
  3. Lynch JW Kaplan GA Berkman LF Kawachi I 2000 Socioeconomic position Social Epidemiology 13 35 Oxford Oxford University Press

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Metadata

Authors
Miller, G. E., Chen, E., & Parker, K. J.
Affiliations
  • University of British Columbia (CA)
  • Stanford Medicine (US)
ORCID
Venue
Psychological Bulletin
Publisher
American Psychological Association (APA)
Published
2011
Volume
137
Issue
6
Pages
959-997
ISSN
  • 0033-2909 (ISSN-L)
  • 1939-1455
DOI
10.1037/a0024768
PMC
PMC3202072
OpenAlex
W2169690159
Cited by
1,785
References
365
Citations by year
2026: 114 · 2025: 129 · 2024: 116 · 2023: 120 · 2022: 166 · 2021: 156 · 2020: 140 · 2019: 119 · 2018: 150 · 2017: 133 · 2016: 133 · 2015: 113 · 2014: 85 · 2013: 72 · 2012: 39
FWCI
24.51
Type
journal article
Language
en
Open access
Locations
  • Psychological Bulletin (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD058502)
  • National Heart, Lung, and Blood Institute (HL073975)
Topics
  • Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
  • Social Sciences › Psychology › Clinical Psychology › Child Abuse and Trauma
  • Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Birth, Development, and Health
Keywords
childhood stress, biological embedding, epigenetics, macrophages, proinflammation, cytokine response, threat vigilance, interpersonal relationships, self-regulation, unhealthy lifestyle, endocrine dysfunction, autonomic dysfunction, vascular disease, autoimmune disease, premature mortality, poverty, child abuse, life course
MeSH terms
Adaptation, Physiological, Aging, Animals, Child, Child Abuse, Child Development, Chronic Disease, Disease Susceptibility, Female, Humans, Inflammation, Life Change Events, Male, Models, Biological, Morbidity, Socioeconomic Factors, Stress, Physiological, Stress, Psychological, Epigenesis, Genetic, Mortality, Premature

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