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 de...

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Published in:European neuropsychopharmacology 2017-04, Vol.27 (4), p.360-371
Main Authors: Schartner, Christoph, Ziegler, Christiane, Schiele, Miriam A, Kollert, Leonie, Weber, Heike, Zwanzger, Peter, Arolt, Volker, Pauli, Paul, Deckert, Jürgen, Reif, Andreas, Domschke, Katharina
Format: Article
Language:English
Subjects:
Adult
Beck Anxiety Inventory
Chi-Square Distribution
Computer Simulation
Corticotropin releasing hormone receptor 1
DNA Methylation - genetics
Epigenesis, Genetic - genetics
Epigenetics
Female
Genotype
HPA axis
Humans
Internal Medicine
Male
Methylation
Middle Aged
Panic disorder
Panic Disorder - genetics
Polymorphism, Single Nucleotide - genetics
Promoter Regions, Genetic - genetics
Psychiatry
Receptors, Corticotropin-Releasing Hormone - genetics
Young Adult
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Summary: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
ISSN:0924-977X
1873-7862
DOI:10.1016/j.euroneuro.2017.01.005