Longitudinal associations between glucocorticoid receptor methylation and late-life depression
Abstract
It has been suggested that hypothalamus-pituitary-adrenal (HPA) axis dysregulation plays a role in the etiology of depression. HPA axis function is mediated by glucocorticoid receptors (GRs), which are influenced by epigenetic mechanisms (DNA methylation). The association between the DNA methylation of the GR gene (nuclear receptor subfamily 3, group C, member 1; NR3C1) and late-life depression as well as the role of NR3C1 methylation in the prediction of the incidence of depression have not yet been investigated. Therefore, we examined the independent and longitudinal effects of the methylation of three CpG sites in exon 1 F of NR3C1 on late-life depression using peripheral blood. In total, 732 Korean community residents aged ≥65 years were assessed; 521 individuals in this group without depression at baseline were followed 2 years later. The Geriatric Mental State Schedule was used to identify depression, and demographic and clinical covariates were evaluated. The effects of NR3C1 methylation (the individual methylation status of three CpG sites and their average values) on current and follow-up depression were calculated using a multivariate logistic regression model. Higher NR3C1 methylation levels at CpG 2 and 3 and the average methylation value were independently associated with the prevalence of depression at baseline. Additionally, a higher NR3C1 methylation level at CpG 2 was associated with depression incidence 2 years later in this population. These findings suggest an association between the methylation of NR3C1 exon 1 F, especially at CpG 2, and depression later in life.
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The depression process and related brain changes have been linked to hyperactivity or dysregulation of the HPA axis.
“The depression process and related brain changes, however, have also been linked to the hyperactivity or dysregulation of the HPA axis [127,130,131,182,212].”
From Biological, Psychological, and Social Determinants of Depression: A Review of Recent Literature (2021) · cites this paper as [130]
There is a complex relationship between the HPA axis, glucocorticoid receptors, epigenetic mechanisms, and psychiatric sequelae.
“There is a complex relationship between the HPA axis, glucocorticoid receptors, epigenetic mechanisms, and psychiatric sequelae [130,212].”
From Biological, Psychological, and Social Determinants of Depression: A Review of Recent Literature (2021) · cites this paper as [130]
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- Authors
- Kang, H.-J., Bae, K.-Y., Kim, S.-W., Shin, I.-S., Kim, H.-R., Shin, M.-G., Yoon, J.-S., & Kim, J.-M.
- Affiliations
- Chonnam National University (KR)
- Dongshin University (KR)
- Corresponding author
- Kim, Jae-Min
- Venue
- Progress in Neuro-Psychopharmacology and Biological Psychiatry
- Publisher
- Elsevier BV
- Published
- 2018-06
- Volume
- 84
- Issue
- Pt A
- Pages
- 56-62
- ISSN
- 0278-5846 (ISSN-L)
- OpenAlex
- W2793223385
- Cited by
- 30
- References
- 51
- Citations by year
- 2025: 5 · 2024: 2 · 2023: 3 · 2022: 3 · 2021: 6 · 2020: 5 · 2019: 3 · 2018: 3
- FWCI
- 1.51
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Progress in Neuro-Psychopharmacology and Biological Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Research Foundation of Korea (2016R1C1B2006793)
- Ministry of Science, ICT and future Planning
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Keywords
- glucocorticoid receptor, NR3C1, DNA methylation, geriatric depression, HPA axis dysregulation, CpG sites, depression incidence, epigenetics, older adults
- MeSH terms
- Aged, Cross-Sectional Studies, Depressive Disorder, Exons, Female, Follow-Up Studies, Humans, Longitudinal Studies, Male, Prospective Studies, Receptors, Glucocorticoid, Prevalence, CpG Islands, DNA Methylation, Epigenesis, Genetic, Republic of Korea
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