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Increased methylation of glucocorticoid receptor gene promoter 1 F in peripheral blood of patients with generalized anxiety disorder
Abstract
Previous findings on the dysfunction of hypothalamic-pituitary-adrenal (HPA) axis in generalized anxiety disorder (GAD) are controversial, and the molecular mechanisms underlying such dysfunction remain unclear. We analyzed the methylation status of the NR3C1 1 F promoter and the expression of glucocorticoid receptor-α isoform (GRα) in peripheral blood mononuclear cells (PMBCs), the basal cortisol level in serum, and a functional neuroendocrine marker for GR sensitivity in the PMBCs in 64 patients with current GAD and 85 healthy controls. We found that patients with GAD had significantly elevated levels of morning basal serum cortisol (P F promoter (P F promoter (P F promoter and decreased GRα expression.
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More than 50% of the GAD group had comorbid depression and approximately 42% smoked.
“Of note, >50% of the GAD group had comorbid depression and ∼42% smoked (Wang et al., 2017).”
From The Epigenetics of Anxiety Pathophysiology: A DNA Methylation and Histone Modification Focused Review (2023) · cites this paper as Wang et al., 2017
Reduced GR expression because of NR3C1 hypomethylation promoted HPA axis hyperactivity and increased cortisol production as a result of decreased negative feedback regulated by GRs.
“These researchers argue that reduced GR expression because of NR3C1 hypomethylation, promoted HPA axis hyperactivity, and increased cortisol production as a result of decreased negative feedback regulated by GRs (Wang et al., 2017).”
From The Epigenetics of Anxiety Pathophysiology: A DNA Methylation and Histone Modification Focused Review (2023) · cites this paper as Wang et al., 2017
The Wang et al. (2017) study is confounded by comorbid depression and substance use.
“though arguably, the Wang et al. (2017) study is also confounded by comorbid depression and substance use.”
From The Epigenetics of Anxiety Pathophysiology: A DNA Methylation and Histone Modification Focused Review (2023) · cites this paper as Wang et al., 2017
Hypermethylation of NR3C1 exon 1F at several CpG sites correlated with decreased mRNA levels of GRα in peripheral blood mononuclear cells of adults diagnosed with generalized anxiety disorder.
“In consensus with increased methylation studies of NR3C1, hypermethylation of exon 1F at several CpG sites correlated with a decrease in the mRNA levels of GRα (one isoform of glucocorticoid receptor) in samples of peripheral blood mononuclear cells (PBMCs) of adults diagnosed with generalized AD (GAD; Wang et al., 2017).”
From The Epigenetics of Anxiety Pathophysiology: A DNA Methylation and Histone Modification Focused Review (2023) · cites this paper as Wang et al., 2017
Individuals in the Wang et al. (2017) study who reported childhood traumatic experiences demonstrated lower levels of methylation compared with non-CTE GAD individuals.
“Individuals in the Wang et al. (2017) study who reported CTEs demonstrated lower levels of methylation compared with non-CTE GAD individuals.”
From The Epigenetics of Anxiety Pathophysiology: A DNA Methylation and Histone Modification Focused Review (2023) · cites this paper as Wang et al., 2017
Higher levels of serum cortisol were detected in individuals with generalized anxiety disorder.
“Higher levels of serum cortisol were also detected in GAD individuals.”
From The Epigenetics of Anxiety Pathophysiology: A DNA Methylation and Histone Modification Focused Review (2023) · cites this paper as Wang et al., 2017
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Hypothalamic-pituitary-adrenal axis, neuroendocrine factors and stress
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Epigenetics at the crossroads between genes, environment and resilience in anxiety disorders
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BackgroundResultInfluential
Metadata
- Authors
- Wang, W., Feng, J., Ji, C., Mu, X., Ma, Q., Fan, Y., Chen, C., Gao, C., Ma, X.-C., & Zhu, F.
- Affiliations
- First Affiliated Hospital of Xi'an Jiaotong University (CN)
- Northwest Women's and Children's Hospital (CN)
- Corresponding author
- Zhu, Feng
- Venue
- Journal of Psychiatric Research
- Publisher
- Elsevier BV
- Published
- 2017-08
- Volume
- 91
- Pages
- 18-25
- ISSN
- 0022-3956 (ISSN-L)
- OpenAlex
- W2591587253
- Cited by
- 49
- References
- 7
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 5 · 2023: 5 · 2022: 8 · 2021: 9 · 2020: 7 · 2019: 1 · 2018: 6 · 2017: 4
- FWCI
- 2.55
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Psychiatric Research (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Keywords
- generalized anxiety disorder, glucocorticoid receptor, DNA methylation, hypothalamic-pituitary-adrenal axis, serum cortisol, peripheral blood mononuclear cells, childhood trauma, epigenetics, glucocorticoid sensitivity
- MeSH terms
- Patient Health Questionnaire, Adult, Anxiety Disorders, Female, Humans, Hydrocortisone, Leukocytes, Mononuclear, Male, Muramidase, Promoter Regions, Genetic, Receptors, Glucocorticoid, RNA, Messenger, CpG Islands, DNA Methylation
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