Associations of DNA methylation of HPA axis-related genes and neuroendocrine abnormalities in panic disorder. (August 2022) - Zou, Zhili
Abstract: Objective: The purpose of this study was to investigate the role of aberrant DNA methylation of hypothalamic-pituitary-adrenal (HPA) axis-related genes ( CRHR1, CRHR2, CRH, FKBP5, HSP90AA1, NR3C1, and POMC ) in panic disorder (PD) development. We investigated the correlation among gene methylation levels, adrenocorticotropic hormone (ACTH), cortisol, and PD severity in patients. Methods: We compared the methylation levels of HPA axis-related genes between 178 patients with PD and 184 healthy controls using MethylTarget. We then measured ACTH and cortisol levels using chemiluminescence. Disease severity was assessed using the Panic Disorder Severity Scale. Results: Compared with healthy controls, patients with PD displayed significantly higher levels of ACTH and cortisol, and significantly reduced methylation levels of CRHR1, FKBP5, HSP90AA1, and NR3C1 after correcting for multiple testing using the false discovery method. A significant positive correlation was observed between the methylation of CRHR1, CRHR2, and NR3C1 and ACTH levels in patients with PD, and methylation levels of CRHR1 and NR3C1 were significantly positively related to cortisol levels. In addition, a negative correlation was observed between PD severity and the methylation of CRH, CRHR1, CRHR2, and HSP90AA1 . Conclusion: Aberrant methylation of HPA axis-related genes may predict PD development and impact ACTH and cortisol levels. Highlights: Patients with PD showed a significantly higher serum levels of ACTH and cortisol than controls. PD patients showed hypomethylation in CRHR1, FKBP5, HSP90AA1 and NR3C1 genes than controls. The methylation of CRHR1, CRHR2 and NR3C1 genes was significantly positively related to the level of ACTH in patients with PD. The methylation of CRHR1 and NR3C1 genes was significantly positively related to the level of cortisol in PD patients.