Associations of DNA methylation of HPA axis-related genes and neuroendocrine abnormalities in panic disorder

Zhili Zou; Miao Xiang; Yuan Zhang; Yulan Huang; Jinyu Wang; Ying He; Wenjiao Min; Bo Zhou

doi:10.1016/j.psyneuen.2022.105777

Associations of DNA methylation of HPA axis-related genes and neuroendocrine abnormalities in panic disorder

Psychoneuroendocrinology. 2022 Aug:142:105777. doi: 10.1016/j.psyneuen.2022.105777. Epub 2022 Apr 27.

Authors

Zhili Zou¹, Miao Xiang², Yuan Zhang³, Yulan Huang⁴, Jinyu Wang⁴, Ying He⁴, Wenjiao Min⁴, Bo Zhou⁵

Affiliations

¹ Provincial Center for Mental Health, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, Chengdu 610072, China; Department of Psychosomatic Medicine, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu 611731, China. Electronic address: zou_zhili@163.com.
² Department of Psychosomatic Medicine, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu 611731, China.
³ Personalized Drug Therapy Key Laboratory of Sichuan Province, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, Chengdu 610072, China.
⁴ Provincial Center for Mental Health, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, Chengdu 610072, China.
⁵ Provincial Center for Mental Health, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, Chengdu 610072, China; Key Laboratory of psychosomatic medicine,Chinese Academy of Medical Sciences, Chengdu 610072, China. Electronic address: tonyac7721@163.com.

PMID: 35504198
DOI: 10.1016/j.psyneuen.2022.105777

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.

Keywords: HPA axis; Methylation; Neuroendocrine hormone; Panic disorder.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adrenocorticotropic Hormone / genetics
DNA Methylation / genetics
Humans
Hydrocortisone
Hypothalamo-Hypophyseal System
Panic Disorder* / genetics
Pituitary-Adrenal System*

Substances

Adrenocorticotropic Hormone
Hydrocortisone