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Cited by 1,433Stress Responses and CortisolAdrenal Hormones and DisordersCancer, Stress, Anesthesia, and Immune Response

Chronic stress, glucocorticoid receptor resistance, inflammation, and disease risk

Open access
Cohen, Sheldon, Janicki-Deverts, Denise, Doyle, William J., Miller, Gregory E., Frank, Ellen, Rabin, Bruce S., Turner, Ronald B.·2012·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.1118355109PMC PMC3341031
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Abstract

We propose a model wherein chronic stress results in glucocorticoid receptor resistance (GCR) that, in turn, results in failure to down-regulate inflammatory response. Here we test the model in two viral-challenge studies. In study 1, we assessed stressful life events, GCR, and control variables including baseline antibody to the challenge virus, age, body mass index (BMI), season, race, sex, education, and virus type in 276 healthy adult volunteers. The volunteers were subsequently quarantined, exposed to one of two rhinoviruses, and followed for 5 d with nasal washes for viral isolation and assessment of signs/symptoms of a common cold. In study 2, we assessed the same control variables and GCR in 79 subjects who were subsequently exposed to a rhinovirus and monitored at baseline and for 5 d after viral challenge for the production of local (in nasal secretions) proinflammatory cytokines (IL-1β, TNF-α, and IL-6). Study 1: After covarying the control variables, those with recent exposure to a long-term threatening stressful experience demonstrated GCR; and those with GCR were at higher risk of subsequently developing a cold. Study 2: With the same controls used in study 1, greater GCR predicted the production of more local proinflammatory cytokines among infected subjects. These data provide support for a model suggesting that prolonged stressors result in GCR, which, in turn, interferes with appropriate regulation of inflammation. Because inflammation plays an important role in the onset and progression of a wide range of diseases, this model may have broad implications for understanding the role of stress in health.

Integrity signals

Registry

Crossref · 10.1073/pnas.1118355109

Cites

39 of 39 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

9 of 33 cited sources checked · 2 supported · 0 flagged · accuracy not yet measured

  • Premisecitation
    § Chronic stress, glucocorticoid receptor resistance, inflammation, and disease risk

    The simple notion that chronic stress acts through the direct effects of elevated circulating cortisol is becoming less likely.

    “The simple notion that chronic stress acts through the direct effects of elevated circulating cortisol is becoming less likely (5,6).”
    Quote in the paperSubstantial claim1 of 2 sources checked
    • cites [5] 5. Cole SW (2008) Social regulation of leukocyte homeostasis: The role of glucocorticoid sensitivity. Brain Behav Immun 22:1049-1055. source

      The Introduction reports glucocorticoid resistance in chronically stressed people, and the Discussion reports reduced leukocyte sensitivity to cortisol among lonely older adults. These findings challenge an explanation based solely on cortisol’s direct effects, but the paper does not establish that elevated circulating cortisol is an increasingly unlikely explanation for chronic stress generally. (LLM, conf=0.82)

      Experimental — accuracy not yet measured
    • cites [6] 6. Meagher MW, Johnson RR, Good E, Welsh TH (2006) Psychoneuroimmunology, eds Ader R, Felton D, Cohen N (Academic, New York), 4th Ed, Vol II, pp 1107-1124. source
  • Premisecitation

    The indirect assessment used here correlates with blunting of lymphocyte redistribution in response to dexamethasone injection.

    “and that the indirect assessment used here correlates with blunting of lymphocyte redistribution in response to dexamethasone injection (24).”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [24] 24. Cole SW, Mendoza SP, Capitanio JP (2009) Social stress desensitizes lymphocytes to regulation by endogenous glucocorticoids: Insights from in vivo cell trafficking dy- namics in rhesus macaques. Psychosom Med 71:591-597. source
  • Premisecitation

    There is a strong physiologic correlation between cortisol levels and the number of circulating leukocytes only if leukocyte glucocorticoid receptors are sensitive.

    “The logic of the measure is that there is a strong physiologic correlation between cortisol levels and the number of circulating leukocytes only if leukocyte glucocorticoid receptors are sensitive (i.e., signaling cells to redistribute).”
    Quote in the paperSubstantial claim2 of 2 sources checked
    • cites [5] 5. Cole SW (2008) Social regulation of leukocyte homeostasis: The role of glucocorticoid sensitivity. Brain Behav Immun 22:1049-1055. source

      The Introduction (page not provided) says cortisol correlates with neutrophil-to-lymphocyte and neutrophil-to-monocyte ratios when leukocyte glucocorticoid receptors are sensitive, and that desensitization attenuates those correlations. But the claim broadens this to the number of circulating leukocytes: Table 2 (Results; page not provided) finds no significant association with total white-blood-cell count. The Discussion also says the observed correlations with hematologic measures rarely exceeded r = .20, so calling them strong overstates the findings. (LLM, conf=0.88)

      Experimental — accuracy not yet measured
    • cites [24] 24. Cole SW, Mendoza SP, Capitanio JP (2009) Social stress desensitizes lymphocytes to regulation by endogenous glucocorticoids: Insights from in vivo cell trafficking dy- namics in rhesus macaques. Psychosom Med 71:591-597. source

      The Introduction says glucocorticoid-receptor signaling mediates leukocyte redistribution and that the strength of its association with cortisol is a measure of sensitivity. But the Results report only a weak correlation for lymphocyte counts (rS = −.20), with no significant association for monocytes or neutrophils. Thus the claim overstates the strength and breadth of the correlation. Page numbers were not available in our copy. (LLM, conf=0.86)

      Experimental — accuracy not yet measured
  • Premisecitation
    § Chronic stress, glucocorticoid receptor resistance, inflammation, and disease risk

    Cortisol levels based on 24-h urine and waking diurnal assessments in saliva do not play a part in the process linking stress to cold susceptibility.

    “However, cortisol levels based on 24-h urine (15) and waking diurnal assessments in saliva (19,20) do not play a part in this process.”
    Quote in the paperSubstantial claim1 of 3 sources checked
    • cites [15] 15. Cohen S, et al. (1998) Types of stressors that increase susceptibility to the common cold in healthy adults. Health Psychol 17:214-223. source
    • cites [19] 19. Cohen S, et al. (2008) Objective and subjective socioeconomic status and susceptibility to the common cold. Health Psychol 27:268-274. source

      The Potential Mediating Variables section lists the measures assessed as pathways to colds but does not include cortisol. The Discussion addresses sleep and psychological variables, not whether cortisol measured in 24-hour urine or waking saliva plays a role. Searches for those cortisol measures and for cortisol as a mediator found no passage establishing the claim. (LLM, conf=0.77)

      Experimental — accuracy not yet measured
    • cites [20] 20. Edwards S, Hucklebridge F, Clow A, Evans P (2003) Components of the diurnal cortisol cycle in relation to upper respiratory symptoms and perceived stress. Psychosom Med 65:320-327. source
  • Premisecitation

    Chronic stress does not appear to affect expression of GRα, the active isoform of the receptor.

    “Chronic stress does not appear to affect expression of GRα, the active isoform of the receptor (11).”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [11] 11. Miller GE, et al. (2008) A functional genomic fingerprint of chronic stress in humans: Blunted glucocorticoid and increased NF-kappaB signaling. Biol Psychiatry 64:266-272. source

      The Results (page not provided) report similar GR mRNA levels in monocytes from chronically stressed caregivers and controls, and the Discussion (page not provided) draws the same conclusion. The paper does not identify the measured mRNA as GRα or establish that expression of that specific isoform was unaffected. (LLM, conf=0.86)

      Experimental — accuracy not yet measured
  • May combine two claims. 20
  • Classified as probably not a substantial claim. 9

  • May combine two claims.

    Premisecitation
    § Chronic stress, glucocorticoid receptor resistance, inflammation, and disease risk

    Evidence for GCR in response to chronic stress has been found in parents of children with cancer, spouses of brain-cancer patients, and persons reporting high levels of loneliness.

    “Evidence for GCR in response to chronic stress has been found in parents of children with cancer (10), spouses of brain-cancer patients (11) and in persons reporting high levels of loneliness (5).”
    Quote in the paperSubstantial claim2 of 3 sources checked
    • cites [10] 10. Miller GE, Cohen S, Ritchey AK (2002) Chronic psychological stress and the regulation of pro-inflammatory cytokines: A glucocorticoid-resistance model. Health Psychol 21: 531-541. source
    • cites [11] 11. Miller GE, et al. (2008) A functional genomic fingerprint of chronic stress in humans: Blunted glucocorticoid and increased NF-kappaB signaling. Biol Psychiatry 64:266-272. source

      The Methods and Results (page numbers unavailable) identify the participants as familial caregivers of brain-cancer patients and report diminished glucocorticoid-related transcription in caregivers versus controls. The copy does not establish that the caregivers were spouses, so it supports the finding but not that specific relationship. (LLM, conf=0.86)

      Experimental — accuracy not yet measured
    • cites [5] 5. Cole SW (2008) Social regulation of leukocyte homeostasis: The role of glucocorticoid sensitivity. Brain Behav Immun 22:1049-1055. source

  • May combine two claims.

    Findingcitation

    We found no effects of cortisol levels on disease risk, GCR, or inflammation.

    “We found no effects of cortisol levels on disease risk (e.g., refs.19, 20), GCR, or inflammation.”
    Quote in the paperSubstantial claim1 of 2 sources checked
    • cites [19] 19. Cohen S, et al. (2008) Objective and subjective socioeconomic status and susceptibility to the common cold. Health Psychol 27:268-274. source

      The citation is attached to the disease-risk portion of the sentence, not the claims about GCR or inflammation. The Data Analysis section reports predictors of clinical colds but does not report an analysis of cortisol levels and disease risk. A mention of cortisol in the introductory material describes another study, not a result of this paper. (LLM, conf=0.73)

      Experimental — accuracy not yet measured
    • cites [20] 20. Edwards S, Hucklebridge F, Clow A, Evans P (2003) Components of the diurnal cortisol cycle in relation to upper respiratory symptoms and perceived stress. Psychosom Med 65:320-327. source

  • May combine two claims.

    Findingown data

    The slopes of the stressed and nonstressed subjects were different from each other, supported by stress-by-cortisol level interactions in linear regressions predicting lymphocytes (P = 0.03), neutrophils (P = 0.03), and the N/L ratio (P = 0.03).

    “That the slopes of the stressed and nonstressed subjects were different from each other is supported by stress-by-cortisol level interactions found in linear regressions predicting lymphocytes (P = 0.03), neutrophils (P = 0.03) and the N/L ratio (P = 0.03).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Cortisol levels as assessed by multiple samples of saliva collected across the day before viral challenge were unrelated to any of the three GCR measures (all P > 0.20) or to proinflammatory cytokine levels (all P > 0.40).

    “Cortisol levels as assessed by multiple samples of saliva collected across the day before viral challenge were unrelated to any of the three GCR measures (all P > 0.20) or to proinflammatory cytokine levels (all P > 0.40).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The correlation of IL-1β GCR with local IL-1β release was in the expected direction, but was not significant.

    “The correlation of IL-1β GCR with local IL-1β release was in the expected direction, but was not significant.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Linear regressions indicate stress-by-cortisol interactions for lymphocytes (P = 0.02), neutrophils (marginal at P = 0.08), and N/L ratio (P = 0.02).

    “Here linear regressions indicate stress-by-cortisol interactions for lymphocytes (P = 0.02), neutrophils (marginal at P = 0.08), and N/L ratio (P = 0.02).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    For all three analyses, simple slopes among those who did not develop a cold were significantly different from 0, whereas slopes for those who did develop a cold were not.

    “For all three analyses, simple slopes among those who did not develop a cold were significantly different from 0, whereas slopes for those who did develop a cold were not (Table 2).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    For all three analyses, simple slopes for those without stress were significantly different from 0, whereas slopes for those with stress were not.

    “For all three analyses, simple slopes for those without stress were significantly different from 0, whereas slopes for those with stress were not (Table 1).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data

    We found consistent evidence across studies 1 and 2, even though study 2 used a standard direct assessment of GCR.

    “We also found consistent evidence across studies 1 and 2, even though study 2 used a standard direct assessment of GCR.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Study design and conductnone given

    The use of multiple control variables eliminates many potential spurious explanations.

    “The use of multiple control variables also eliminates many potential spurious explanations.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationreasoning

    Because the analyses in both studies were prospective, we can eliminate reverse causation (colds did not cause stress, colds did not cause GCR, and cytokine release did not cause GCR) as an alternative explanation.

    “Because the analyses in both studies were prospective, we can eliminate reverse causation (colds did not cause stress, colds did not cause GCR, and cytokine release did not cause GCR) as an alternative explanation.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation
    § Chronic stress, glucocorticoid receptor resistance, inflammation, and disease risk

    Without sufficient glucocorticoid regulation, the duration and/or intensity of the inflammatory response increases, heightening risk for acute exacerbations such as occur in asthma and autoimmune diseases, as well as for the onset and progression of chronic inflammatory diseases such as CVD and type II diabetes.

    “Without sufficient glucocorticoid regulation, the duration and/or intensity of the inflammatory response increases, heightening risk for acute exacerbations such as occur in asthma and autoimmune diseases, as well as for the onset and progression of chronic inflammatory diseases such as CVD, and type II diabetes (12).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [12] 12. Nathan C (2002) Points of control in inflammation. Nature 420:846-852. source

  • May combine two claims.

    Study design and conductreasoning

    Health is not an issue here, because subjects are carefully screened for excellent health.

    “Health is not an issue here, because subjects are carefully screened for excellent health.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning

    Because inflammation plays a role in progression of multiple diseases, this model not only provides an explanation for the increased risk for URI under stress, but might provide a more general explanation for why prolonged stress would play a role in other inflammatory diseases as well.

    “Because inflammation plays a role in progression of multiple diseases, this model not only provides an explanation for the increased risk for URI under stress, but might provide a more general explanation for why prolonged stress would play a role in other inflammatory diseases as well.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Inflammation plays an important role in the onset and progression of a wide range of diseases.

  • May combine two claims.

    Premisecitation

    Greater levels of glucocorticoid are associated with higher numbers of circulating neutrophils, lower numbers of circulating lymphocytes, and a lower neutrophil-to-lymphocyte ratio.

    “Greater levels of glucocorticoid are associated with higher numbers of circulating neutrophils, lower numbers of circulating lymphocytes, and a lower neutrophil-to-lymphocyte (N/L) ratio-an overall marker of the trafficking of these cells (e.g., refs.22,23).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [22] 22. Fauci AS, Dale DC, Balow JE (1976) Glucocorticosteroid therapy: Mechanisms of action and clinical considerations. Ann Intern Med 84:304-315. source
    • cites [23] 23. Dhabhar FS, Miller AH, McEwen BS, Spencer RL (1996) Stress-induced changes in blood leukocyte distribution. Role of adrenal steroid hormones. J Immunol 157:1638-1644. source

  • Probably not a substantial claim: may not pass S2 (checkable), S4 (based).

    Premisenone given
    § Chronic stress, glucocorticoid receptor resistance, inflammation, and disease risk

    The viral-challenge paradigm provides an ideal context to study the general model of stress leading to disease via effects on the HPA and inflammatory regulation.

    “The viral-challenge paradigm provides an ideal context to study the general model of stress leading to disease via effects on the HPA and inflammatory regulation.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationown data

    These data are consistent with a model wherein stress leads to GCR, which in turn results in greater risk for developing a cold.

    “These data are consistent with a model wherein stress leads to GCR, which in turn results in greater risk for developing a cold.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data

    GCR predicts an increased risk for colds following viral exposure, whereas levels of circulating cortisol do not.

    “Together, results from these prospective analyses support the hypothesis that GCR predicts an increased risk for colds following viral exposure, whereas levels of circulating cortisol do not.”
    • Also stated in: § Discussion · plain
      “In turn, GCR was prospectively associated with increased risk of developing a common cold following experimental inoculation with a cold virus.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductown data

    Ratings of events were performed in an independent laboratory by consensus groups consisting of at least four trained interviewers, with interview staff blind to other study measures and raters blind to individuals' subjective responses.

    “Ratings of events were performed in an independent laboratory by consensus groups consisting of at least four trained interviewers.”
    • Also stated in: § Methods · plain
      “The interview staff was blind to other study measures.”
    • Also stated in: § Methods · plain
      “Raters were also blind to individuals' subjective responses to the stressful events”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    GRβ is a dominant negative receptor for cortisol, which can suppress GRα activity and thereby contribute to GCR.

    “This could prove important because GRβ is a dominant negative receptor for cortisol, which can suppress GRα activity and thereby contribute to GCR (28).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [28] 28. Derijk RH, et al. (2001) A human glucocorticoid receptor gene variant that increases the stability of the glucocorticoid receptor beta-isoform mRNA is associated with rheumatoid arthritis. J Rheumatol 28:2383-2388.

  • Classified as probably not a substantial claim.

    Study design and conductcitation

    Stressful life events were assessed by a standardized semistructured interview, the Bedford College Life Events and Difficulties Schedule (LEDS), conducted by trained interviewers.

    “Life events were assessed by a standardized semistructured interview, the Bedford College Life Events and Difficulties Schedule (LEDS) (29), and conducted by trained interviewers.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [29] 29. Brown GW, Harris TO (1989) Life Events and Illness (Guilford, New York).

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    All investigators were blinded to subjects' status on all baseline assessments.

    “All investigators were blinded to subjects' status on all baseline assessments.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    Three subjects were excluded due to incomplete nasal cytokine data.

    “Three subjects were excluded due to incomplete nasal cytokine data.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    The investigators were blinded to all baseline measures in study 2.

    “The investigators were blinded to all baseline measures.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Study design and conductown data

    Correlations between cell counts from the two blood draws ranged from 0.61 to 0.76, P < 0.001, and the correlation between cortisol in the two samples was 0.70, P < 0.001.

    “Correlations between cell counts from the two blood draws ranged from 0.61 to 0.76, P < 0.001.”
    • Also stated in: § Methods · plain
      “The correlation between cortisol in the two samples was 0.70, P < 0.001.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Study design and conductcitation

    We used a standard in vitro assay to measure GCR that assessed the ability of dexamethasone to suppress lipopolysaccharide-stimulated lymphocyte production of IL-1β, IL-6, and TNFα.

    “We used a standard in vitro assay to measure GCR that assessed the ability of dexamethasone (0, 10, 50, and 250 nM) to suppress lipopolysaccharide (30 ng/mL) stimulated lymphocyte production of IL-1β, IL-6, and TNFα.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [6] 6. Meagher MW, Johnson RR, Good E, Welsh TH (2006) Psychoneuroimmunology, eds Ader R, Felton D, Cohen N (Academic, New York), 4th Ed, Vol II, pp 1107-1124. source

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Proinflammatory cytokines are thought to both up-regulate immunity to the virus and produce cold symptoms.

    “Parodoxically, proinflammatory cytokines are thought to both up-regulate immunity to the virus and produce cold symptoms (13).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [13] 13. Hendley JO (1998) The host response, not the virus, causes the symptoms of the common cold. Clin Infect Dis 26:847-848. source
27 of 27

  • The paper relies on this without support.

    Inflammation plays an important role in the onset and progression of a wide range of diseases.

    “Because inflammation plays an important role in the onset and progression of a wide range of diseases, this model may have broad implications for understanding the role of stress in health.”

  • The paper relies on this without support.

    Few human studies include assessments of stressful events, HPA response, and a disease outcome in the same subjects.

    “few human studies include assessments of stressful events, HPA response, and a disease outcome in the same subjects.”
2 of 2

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?

  • Exposure to chronic stress promotes sustained, non-resolving inflammation within the CNS through the gradual development of glucocorticoid resistance, which further drives inflammation.

    “However, exposure to chronic stress promotes sustained, non-resolving inflammation within the CNS through the gradual development of glucocorticoid resistance, which further drives inflammation.”

    From The Role of Cortisol in Chronic Stress, Neurodegenerative Diseases, and Psychological Disorders (2023) · cites this paper as [22]

    The paper's introductory model says chronic stress may produce glucocorticoid receptor resistance, reducing control of inflammation and increasing its duration or intensity. Its study of inflammatory cytokines measures responses in nasal secretions after viral challenge, not inflammation within the CNS. The copy also does not establish gradual development or sustained, non-resolving inflammation. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • Once glucocorticoid resistance develops, the "fight or flight" response to social threats is altered and results in exaggerated inflammation, consequently perpetuating the proinflammatory state.

    “Once GC resistance develops, the “fight or flight” response to social threats is altered and results in exaggerated inflammation, consequently perpetuating the proinflammatory state [22].”

    From The Role of Cortisol in Chronic Stress, Neurodegenerative Diseases, and Psychological Disorders (2023) · cites this paper as [22]

    The paper’s Discussion reports that glucocorticoid receptor resistance predicted greater local proinflammatory cytokine production after viral infection. Its introductory discussion also says reduced glucocorticoid regulation can increase the duration or intensity of inflammation. It does not establish that the fight-or-flight response to social threats is altered or that this perpetuates a proinflammatory state; the tested response was to infection. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

  • ELS/CT together with higher cortisol during the stress hypo-responsive period could lead to glucocorticoid-receptor insensitivity through greater exposure to glucocorticoids over time, altering physiological HPA axis development.

    “ELS/CT together with higher cortisol during this SHRP could possibly lead to GR insensitivity through greater exposure to GC over time, thus altering the physiological of HPA axis development (101, 112).”

    From Developmental Trajectories of Early Life Stress and Trauma: A Narrative Review on Neurobiological Aspects Beyond Stress System Dysregulation (2019) · cites this paper as [112]

    The Discussion (page unavailable) reports that stressful life experiences were associated with glucocorticoid-receptor resistance, supporting the stress-to-insensitivity part of the claim. It does not address early-life stress during the stress hypo-responsive period or altered HPA-axis development. The Discussion also reports no effect of cortisol levels on receptor resistance, so it does not support the proposed mechanism of greater glucocorticoid exposure over time. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • The presence of these FKBP5 alleles can result in low levels of circulating cortisol and/or GR resistance in PTSD, which can lead to a pro-inflammatory state via decreases in anti-inflammatory GR signaling.

    “Thus, the presence of these FKPB5 alleles can result in low levels of circulating cortisol and/or GR resistance in PTSD can lead to a pro-inflammatory state via decreases in antiinflammatory GR signaling (Cohen et al, 2012).”

    From Inflammation in Fear- and Anxiety-Based Disorders: PTSD, GAD, and Beyond (2017) · cites this paper as Cohen et al, 2012

    The Discussion (page unavailable) supports the general mechanism: glucocorticoid receptor resistance can impair cortisol's regulation of proinflammatory cytokines. The paper does not link FKBP5 alleles or PTSD to that mechanism, and its Discussion reports no effect of circulating cortisol levels on receptor resistance or inflammation. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • In glucocorticoid resistance due to chronic stress, immune cells demonstrate decreased sensitivity to glucocorticoids, so cortisol release does not result in significant anti-inflammatory effects as would otherwise be expected.

    “In the case of GC resistance due to chronic stress, immune cells demonstrate decreased sensitivity to glucocorticoids. Therefore, in this case, cortisol release does not result in significant anti-inflammatory effects, as one would otherwise expect.”

    From The Role of Cortisol in Chronic Stress, Neurodegenerative Diseases, and Psychological Disorders (2023) · cites this paper as [22]

Self-check

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

Each contradiction between two passages listed here was confirmed by an independent check.

  • Reported cold-status slope analysis does not match the specified regression

    Minor

    The methods specify a stress-by-cold-status interaction for the second set of regressions and do not include cortisol in that model. That model cannot yield the reported cortisol slopes for people with and without colds; the results instead describe a stress-by-cortisol interaction.

1 of 1

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Authors
Cohen, S., Janicki-Deverts, D., Doyle, W. J., Miller, G. E., Frank, E., Rabin, B. S., & Turner, R. B.
Affiliations
  • Carnegie Mellon University (US)
  • Department of Psychology, Carnegie Mellon University, Pittsburgh, PA 15213;
  • Children's Hospital of Pittsburgh (US)
  • University of British Columbia (CA)
  • University of Pittsburgh (US)
  • University of Virginia (US)
ORCID
Venue
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences
Published
2012-04-02
Volume
109
Issue
16
Pages
5995-5999
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
DOI
10.1073/pnas.1118355109
PMC
PMC3341031
OpenAlex
W2125978064
Cited by
1,419
References
36
Citations by year
2026: 114 · 2025: 112 · 2024: 101 · 2023: 156 · 2022: 114 · 2021: 136 · 2020: 123 · 2019: 103 · 2018: 97 · 2017: 107 · 2016: 67 · 2015: 73 · 2014: 70 · 2013: 31 · 2012: 14
FWCI
25.06
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • KiltHub Repository (submittedVersion)
  • Figshare (submittedVersion, cc-by)
  • KiltHub Repository
Funders
  • John D. and Catherine T. MacArthur Foundation
  • National Institutes of Health (5r01mh047234-03, 5r01mh050430-04)
  • National Heart, Lung, and Blood Institute (HL65111, HL65112, P50HL065112, P50HL065111)
  • National Institute of Mental Health (MH-47234, MH 50430)
  • National Center for Complementary and Alternative Medicine (AT006694)
  • National Center for Complementary and Integrative Health (R01AT006694, AT006694)
Topics
  • Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
  • Health Sciences › Medicine › Psychiatry and Mental health › Cancer, Stress, Anesthesia, and Immune Response
Keywords
chronic stress, inflammation, rhinovirus infection, common cold, inflammatory cytokines, IL-1β, TNF-α, interleukin-6, life events, disease risk, stress and health
MeSH terms
Adult, Chronic Disease, Common Cold, Disease Susceptibility, Female, Humans, Hydrocortisone, Inflammation, Leukocyte Count, Male, Middle Aged, Models, Psychological, Quarantine, Receptors, Glucocorticoid, Rhinovirus, Risk Factors, Stress, Psychological, Cytokines, Nasal Lavage Fluid, Young Adult

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