ArticleTranslational psychiatry2023
Methylation and expression of glucocorticoid receptor exon-1 variants and FKBP5 in teenage suicide-completers.
Article in Translational psychiatry, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.
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Who cites it
20 citing papers in PubMed, 1 synthesis or guideline pooled it, 26 citations in OpenAlex.
- Cortisol levels and depression suicide risk: a combined exploration of meta-analysis and case-control study.Frontiers in psychiatry · 2025Pooled it
- Pursuing the elusive biosignature for suicide: a decennial update.Molecular psychiatry · 2026Review
- Prenatal stress shapes discrete responses during early recovery from repeated adult stress.Frontiers in cellular neuroscience · 2026Article
- From synapse to system: mechanistic pathways of neural signaling dysfunction in psychiatric disorders.Frontiers in cell and developmental biology · 2026Review
- Molecular pathways linking chronic psychological stress to accelerated aging: mechanisms and interventions.Frontiers in aging · 2026Review
- Gender differences in gray matter volume of the anterior cingulate cortex and suicidal ideation in patients with major depressive disorder: evidence from the REST-meta-MDD project.Translational psychiatry · 2025Article
- Toward Understanding and Halting Legacies of Trauma.Biological psychiatry · 2025Review
- Epigenetics and immunology: Under-recognized aspects of suicidality.World journal of psychiatry · 2025Review
- Dad's legacy: Epigenetic reprogramming and paternal inflammatory memory in offspring health.Journal of internal medicine · 2025Review
- Genetic, Epigenetic, and Hormonal Regulation of Stress Phenotypes in Major Depressive Disorder: From Maladaptation to Resilience.Cellular and molecular neurobiology · 2025Review
- Epigenetics and suicidal behavior in adolescents: a critical review.Epigenomics · 2025Review
- Structural brain changes in the anterior cingulate cortex of major depressive disorder individuals with suicidal ideation: Evidence from the REST-meta-MDD project.Psychological medicine · 2025Article
- SKA2 enhances stress-related glucocorticoid receptor signaling through FKBP4-FKBP5 interactions in neurons.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Targeting glucocorticoid receptor signaling pathway for treatment of stress-related brain disorders.Pharmacological reports : PR · 2024Review
- The Glucocorticoid Receptor: Isoforms, Functions, and Contribution to Glucocorticoid Sensitivity.Endocrine reviews · 2024Review
- Hormetic Nutrition and Redox Regulation in Gut-Brain Axis Disorders.Antioxidants (Basel, Switzerland) · 2024Review
- Molecular Changes Associated with Suicide.International journal of molecular sciences · 2023Review
- Article
- Strong associations of telomere length and mitochondrial copy number with suicidality and abuse history in adolescent depressed individuals.Molecular psychiatry · 2023Article
- Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
A dysregulated hypothalamic-pituitary-adrenal (HPA) axis has repeatedly been demonstrated to play a fundamental role in psychiatric disorders and suicide, yet the mechanisms underlying this dysregulation are not clear. Decreased expression of the glucocorticoid receptor (GR) gene, which is also susceptible to epigenetic modulation, is a strong indicator of impaired HPA axis control. In the context of teenage suicide-completers, we have systematically analyzed the 5'UTR of the GR gene to determine the expression levels of all GR exon-1 transcript variants and their epigenetic state. We also measured the expression and the epigenetic state of the FK506-binding protein 51 (FKBP5/FKBP51), an important modulator of GR activity. Furthermore, steady-state DNA methylation levels depend upon the interplay between enzymes that promote DNA methylation and demethylation activities, thus we analyzed DNA methyltransferases (DNMTs), ten-eleven translocation enzymes (TETs), and growth arrest- and DNA-damage-inducible proteins (GADD45). Focusing on both the prefrontal cortex (PFC) and hippocampus, our results show decreased expression in specific GR exon-1 variants and a strong correlation of DNA methylation changes with gene expression in the PFC. FKBP5 expression is also increased in both areas suggesting a decreased GR sensitivity to cortisol binding. We also identified aberrant expression of DNA methylating and demethylating enzymes in both brain regions. These findings enhance our understanding of the complex transcriptional regulation of GR, providing evidence of epigenetically mediated reprogramming of the GR gene, which could lead to possible epigenetic influences that result in lasting modifications underlying an individual's overall HPA axis response and resilience to stress.
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Registered trials
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.