Correlation between hypothalamic-pituitary-adrenal axis gene polymorphisms and posttraumatic stress disorder symptoms

Kunlin Zhang; Li Wang; Gen Li; Chengqi Cao; Ruojiao Fang; Ping Liu; Shu Luo; Xiangyang Zhang

doi:10.1016/j.yhbeh.2019.104604

Correlation between hypothalamic-pituitary-adrenal axis gene polymorphisms and posttraumatic stress disorder symptoms

Horm Behav. 2020 Jan:117:104604. doi: 10.1016/j.yhbeh.2019.104604. Epub 2019 Nov 6.

Authors

Kunlin Zhang¹, Li Wang², Gen Li¹, Chengqi Cao³, Ruojiao Fang¹, Ping Liu⁴, Shu Luo⁴, Xiangyang Zhang¹

Affiliations

¹ Laboratory for Traumatic Stress Studies and Center for Genetics and BioMedical Informatics Research, CAS Key Laboratory of Mental Health, Institute of Psychology, Beijing 100101, China; Department of Psychology, University of Chinese Academy of Sciences, Beijing 100049, China.
² Laboratory for Traumatic Stress Studies and Center for Genetics and BioMedical Informatics Research, CAS Key Laboratory of Mental Health, Institute of Psychology, Beijing 100101, China; Department of Psychology, University of Chinese Academy of Sciences, Beijing 100049, China. Electronic address: wangli1@psych.ac.cn.
³ Laboratory for Traumatic Stress Studies and Center for Genetics and BioMedical Informatics Research, CAS Key Laboratory of Mental Health, Institute of Psychology, Beijing 100101, China; Shenzhen Key Laboratory of Affective and Social Cognitive Science, Shenzhen University, Shenzhen 518060, China.
⁴ People's Hospital of Deyang City, Deyang, Sichuan 618000, China.

PMID: 31655035
DOI: 10.1016/j.yhbeh.2019.104604

Abstract

Background: The hypothalamic-pituitary-adrenal (HPA) axis is the main neuroendocrine system that controls stress responses, including fear learning. To further understand the correlation between the HPA axis and stress- and fear-related symptoms in humans, the current study investigated the relationship between HPA axis gene polymorphisms and a stress- and fear-related disorder, posttraumatic stress disorder (PTSD). This is the first study that systematically investigates the correlations between HPA axis genes and distinct PTSD symptom clusters.

Methods: Participants included 1132 Chinese earthquake survivors (772 women and 360 men). PTSD symptoms were measured by the PTSD Checklist for DSM-5 (PCL-5), and the severity (total symptoms) and symptom clusters were calculated according to the hybrid seven-factor model of DSM-5 PTSD. We genotyped eight single nucleotide polymorphisms (SNPs) of three HPA axis genes, including FKBP5, CRHR1 and CRHR2.

Results: The main effects of the CRHR2 SNP rs2267715 were associated with PTSD severity (P = 0.0035) and all PTSD symptom clusters except dysphoric arousal (P ranging from 0.0011 to 0.048). In women, a gene-environment interaction (G × E) effect of FKBP5 (rs3800373 × trauma exposure) was correlated with PTSD severity (P = 0.038), externalizing behaviors, anxious arousal and dysphoric arousal symptoms (P ranging from 0.014 to 0.028); the G × E effect of CRHR1 (rs4458044 × trauma exposure) was associated with anxious arousal symptoms (P = 0.016). In men, a gene-gene interaction (G × G) effect of FKBP5-CRHR1 (rs9470080 × rs4458044) was associated with PTSD severity (P = 0.0091), intrusion, negative affect, externalizing behaviors and anxious arousal (P ranging 0.012-0.049).

Conclusion: Our results systematically revealed that the main effects and G × E and G × G effects of some genetic polymorphisms of HPA axis genes are involved in the severity and distinct symptom clusters of PTSD.

Keywords: Gene; Hypothalamic-pituitary-adrenal (HPA) axis; Posttraumatic stress disorder (PTSD); Stress response; Symptoms.

Publication types

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

MeSH terms

Adolescent
Adult
Aged
Anxiety / etiology
Anxiety / genetics
China
Cohort Studies
Earthquakes
Female
Gene-Environment Interaction
Humans
Hypothalamo-Hypophyseal System / metabolism*
Hypothalamo-Hypophyseal System / physiopathology
Male
Middle Aged
Pituitary-Adrenal System / metabolism*
Pituitary-Adrenal System / physiopathology
Polymorphism, Single Nucleotide*
Stress Disorders, Post-Traumatic / genetics*
Stress Disorders, Post-Traumatic / metabolism
Stress Disorders, Post-Traumatic / physiopathology
Stress, Psychological / genetics*
Stress, Psychological / metabolism
Stress, Psychological / physiopathology
Survivors
Young Adult