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ORIGINAL RESEARCH article
Front. Epigenet. Epigenom.
Sec. Epigenetics and Metabolism
Volume 2 - 2024 |
doi: 10.3389/freae.2024.1435634
This article is part of the Research Topic Current Insights in Epigenetics and Epigenomics View all 8 articles
Blood DNA methylation of CRF and its association with amygdala volume and mood in Cushing's syndrome.
Provisionally accepted- 1 Johns Hopkins Medicine, Johns Hopkins University, Baltimore, Maryland, United States
- 2 Department of Endocrinology, Hospital de la Santa Creu I Sant Pau, Research Center for Pitui-tary Diseases, Institut de Recerca Sant Pau, Barcelona, Spain
- 3 Department of Medicine, Universitat Autonoma de Barcelona, Barcelona, Spain
- 4 Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, United States
- 5 Department of Medicine, Faculty of Medicine, University of Vic - Central University of Catalonia, Vic, Catalonia, Spain
- 6 IDAL, Electronic Engineering Department, ETSE-UV, University of Valencia, Valencia, Spain
Objective: The impact of chronic exposure to stress or glucocorticoids on psychiatric symptoms has been exemplified by cases of iatrogenic or endogenous hypercortisolism such as Cushing's syndrome (CS). The amygdala plays an important role in mediating both stress and affective responses, and one of the key factors that link stress response and psychiatric symptoms is the corticotropin-releasing factor (CRF). Epigenetic changes, especially those occurring on CpG dinucleotides in DNA of glucocorticoid target genes in blood, have been previously implicated as potential predictors of glucocorticoid-related events in the central nervous system (CNS). In this study, we examined amygdala volume and mood symptoms in CS patients and aimed at evaluating whether these parameters were associated with blood DNA methylation of CRF.Methods: In this cross-sectional study, 32 CS patients and 32 healthy controls matched for age, sex, and years of education underwent an MRI scan, a Beck Depression Inventory-II, and a State-Trait Anxiety Inventory. Genomic DNA extracted from total leukocytes were used for DNA methylation analysis of several CpG dinucleotides at the CRF promoter region.Results: Significant associations between CRF methylation vs. amygdala volume (CpG-1, P=0.006) and depression scores (CpG-2, P=0.01) were found. To assess whether the promoter CpG methylation has functional consequences, we examined RNA and DNA extracted from non-CS, postmortem amygdala tissues. A significant association between CpG methylation and gene expression (CpG-1, P=0.004) was observed.Conclusion: These results demonstrate that methylation levels of the CRF promoter CpGs are associated with amygdala volume in CS and related mood symptoms. Methylation levels may also be associated with CRF expression. This finding supports the feasibility of using epigenetic patterns in blood as a surrogate for assessing GC-related pathologies in the brain.
Keywords: Cushing's syndrome, Hypercortisolism, Corticotropin-releasing factor, DNA Methylation, Amygdala
Received: 20 May 2024; Accepted: 23 Aug 2024.
Copyright: © 2024 Lee, Santos, Garrison-Desany, Aulinas, Carey, Vives-Gilabert, Cox, Cuilan, Webb and Resmini. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Richard S. Lee, Johns Hopkins Medicine, Johns Hopkins University, Baltimore, 21218, Maryland, United States
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