Evidence map›Paper›PMID 33221485›Full record

ArticleBrain, behavior, and immunity2021

HPA axis regulation and epigenetic programming of immune-related genes in chronically stressed and non-stressed mid-life women.

Helena Palma-Gudiel, Aric A Prather, Jue Lin, Jake D Oxendine, Jerry Guintivano, Kai Xia, David R Rubinow, Owen Wolkowitz, Elissa S Epel, Anthony S Zannas

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Brain, behavior, and immunity, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed
1.0field-weighted citation impact, top 25% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

23 citing papers in PubMed, 38 citations in OpenAlex.

  1. Review
  2. Article
  3. Review
  4. Review
  5. Review
  6. Review
  7. Review
  8. Article
  9. Review
  10. Review
  11. Article
  12. Review
  13. Article
  14. Article
  15. Review
  16. Immune Homeostasis: A Novel Example of Teamwork.Methods in molecular biology (Clifton, N.J.) · 2024
    Article
  17. Review
  18. Article
  19. Review
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 2 institutions in 2 countries.

Helena Palma-GudielDepartment of Psychiatry, University of North Carolina, Chapel Hill, NC, USA; Centro de Investigación Biomédica en Red en Salud Mental (CIBERSAM), Madrid, Spain.
Aric A PratherDepartment of Psychiatry and Behavioral Sciences and Weill Institute for Neurosciences, University of California, San Francisco, United States.
Jue LinDepartment of Biochemistry and Biophysics, University of California, San Francisco, United States.
Jake D OxendineDepartment of Psychiatry, University of North Carolina, Chapel Hill, NC, USA.
Jerry GuintivanoDepartment of Psychiatry, University of North Carolina, Chapel Hill, NC, USA.
Kai XiaDepartment of Psychiatry, University of North Carolina, Chapel Hill, NC, USA.
David R RubinowDepartment of Psychiatry, University of North Carolina, Chapel Hill, NC, USA.
Owen WolkowitzDepartment of Psychiatry and Behavioral Sciences and Weill Institute for Neurosciences, University of California, San Francisco, United States.
Elissa S EpelDepartment of Psychiatry and Behavioral Sciences, and Center for Health and Community, University of California, San Francisco, CA, USA.
Anthony S ZannasDepartment of Psychiatry, University of North Carolina, Chapel Hill, NC, USA; Department of Genetics, University of North Carolina, Chapel Hill, NC, USA; Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC, USA; Carolina Stress Initiative, University of North Carolina School of Medicine, Chapel Hill, NC, USA. Electronic address: anthony_zannas@med.unc.edu.
University of North Carolina at Chapel Hill · USUniversity of California, San Francisco · US

Funding

Chronic and Acute Psychosocial Stress and Impaired Cell AgingR01AG030424 · NIA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI EPEL, ELISSA S. · 2010 to 2014
$3.5M
Examining the reciprocal effects of racial discrimination and sleep on cardiovascular functioning: An experimental approachR01HL142051 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI PRATHER, ARIC ANDREW · 2018 to 2022
$3.5M
Chronic and Acute Psychosocial Stress and Impaired Cell AgingR56AG030424 · NIA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI EPEL, ELISSA S. · 2008 to 2009
$260k
NHLBI NIH HHS R01 HL142051NIA NIH HHS R01 AG030424NIA NIH HHS R56 AG030424
6 · The paper itself

Abstract

Hypothalamic-pituitary-adrenal (HPA) axis dysregulation has been associated with altered immune function, but the underlying molecular mechanisms are unclear. Epigenetic processes, including DNA methylation, respond to the glucocorticoid end-products of the HPA axis (cortisol in humans) and could be involved in this neuroendocrine-immune crosstalk. Here we examined the extent to which variations in HPA axis regulation are associated with peripheral blood DNA (CpG) methylation changes in 57 chronically stressed caregivers and 67 control women. DNA methylation was determined with the Illumina 450k array for a panel of genes involved in HPA axis and immune function. HPA axis feedback was assessed with the low-dose dexamethasone suppression test (DST), measuring the extent to which cortisol secretion is suppressed by the synthetic glucocorticoid dexamethasone. After multiple testing correction in the entire cohort, higher post-DST cortisol, reflecting blunted HPA axis negative feedback, but not baseline waking cortisol, was associated with lower DNA methylation at eight TNF and two FKBP5 CpG sites. Caregiver group status was associated with lower methylation at two IL6 CpG sites. Since associations were most robust with TNF methylation (32% of the 450k-covered sites), we further examined functionality of this epigenetic signature in cultured peripheral blood mononuclear cells in 33 participants; intriguingly, lower TNF methylation resulted in higher ex vivo TNF mRNA following immune stimulation. Taken together, our findings link chronic stress and HPA axis regulation with epigenetic signatures at immune-related genes, thereby providing novel insights into how aberrant HPA axis function may contribute to heightened inflammation and disease risk.

Indexed as

Hypothalamo-Hypophyseal SystemPituitary-Adrenal SystemDexamethasoneEpigenesis, GeneticFemaleHumansHydrocortisoneLeukocytes, MononuclearDexamethasoneHydrocortisoneCaregivingDexamethasone suppression testDNA methylationFKBP5HPA axisInflammationInterleukin 6TNF

Identifiers

PMID33221485
PMCPMC7897273
OpenAlexW3105045842

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.