CRHR1 promoter hypomethylation: An epigenetic readout of panic disorder?
Abstract
The corticotropin releasing hormone receptor 1 (CRHR1) is crucially involved in the hypothalamic-pituitary-adrenal axis and thus a major regulator of the stress response. CRHR1 gene variation is associated with several mental disorders including anxiety disorders. Studies in rodents have demonstrated epigenetic regulation of CRHR1 gene expression to moderate response to stressful environment. In the present study, we investigated CRHR1 promoter methylation for the first time regarding its role in panic disorder applying a case-control approach (N=131 patients, N=131 controls). In an independent sample of healthy volunteers (N=255), CRHR1 methylation was additionally analyzed for association with the Beck Anxiety Inventory (BAI) score as a dimensional panic-related intermediate phenotype. The functional relevance of altered CRHR1 promoter methylation was investigated by means of luciferase-based reporter gene assays. In panic disorder patients, a significantly decreased CRHR1 methylation was discerned (p<0.001). Accordingly, healthy controls with high BAI scores showed significantly decreased CRHR1 methylation. Functional analyses revealed an increased gene expression in presence of unmethylated as compared to methylated pCpGl_CRHR1 reporter gene vectors. The present study identified a potential role of CRHR1 hypomethylation - conferring increased CRHR1 expression - in panic disorder and a related dimensional intermediate phenotype. This up-regulation of CRHR1 gene expression driven by de-methylation might constitute a link between the stress response and panic disorder risk.
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Crhr1 hypomethylation is a possible diagnostic marker for panic disorder and other anxiety disorders.
“making Crhr1 hypomethylation a possible diagnostic marker for panic disorder and other ADs (Schartner et al., 2017).”
From The Epigenetics of Anxiety Pathophysiology: A DNA Methylation and Histone Modification Focused Review (2023) · cites this paper as Schartner et al., 2017
Similar hypomethylation findings were observed in peripheral blood samples of patients diagnosed specifically with panic disorder.
“Similar findings were observed in peripheral blood samples of patients diagnosed specifically with panic disorder, making Crhr1 hypomethylation a possible diagnostic marker for panic disorder and other ADs (Schartner et al., 2017).”
From The Epigenetics of Anxiety Pathophysiology: A DNA Methylation and Histone Modification Focused Review (2023) · cites this paper as Schartner et al., 2017
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- Authors
- Schartner, C., Ziegler, C., Schiele, M. A., Kollert, L., Weber, H., Zwanzger, P., Arolt, V., Pauli, P., Deckert, J., Reif, A., & Domschke, K.
- Affiliations
- University of Würzburg (DE)
- Goethe University Frankfurt (DE)
- University of Münster (DE)
- University of Freiburg (DE)
- Corresponding author
- Domschke, Katharina
- ORCID
- Venue
- European Neuropsychopharmacology
- Publisher
- Elsevier BV
- Published
- 2017-04
- Volume
- 27
- Issue
- 4
- Pages
- 360-371
- ISSN
- 0924-977X (ISSN-L)
- OpenAlex
- W2590149137
- Cited by
- 53
- References
- 8
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 5 · 2023: 6 · 2022: 8 · 2021: 5 · 2020: 9 · 2019: 5 · 2018: 9 · 2017: 2
- FWCI
- 2.79
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- European Neuropsychopharmacology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Deutsche Forschungsgemeinschaft (SFB-TRR-58)
- Bundesministerium für Bildung und Forschung (01EE1402A)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
- Keywords
- CRHR1, corticotropin-releasing hormone receptor 1, promoter hypomethylation, DNA methylation, panic disorder, anxiety, epigenetics, hypothalamic-pituitary-adrenal axis, stress response, endophenotypes, gene expression regulation
- MeSH terms
- CRF Receptor, Type 1, Adult, Computer Simulation, Female, Genotype, Humans, Male, Middle Aged, Promoter Regions, Genetic, Chi-Square Distribution, Panic Disorder, Receptors, Corticotropin-Releasing Hormone, DNA Methylation, Polymorphism, Single Nucleotide, Epigenesis, Genetic, Young Adult
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