Correlation between hypothalamic-pituitary-adrenal axis gene polymorphisms and posttraumatic stress disorder symptoms.
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.
['Zhang|Kunlin|K|', 'Wang|Li|L|', 'Li|Gen|G|', 'Cao|Chengqi|C|', 'Fang|Ruojiao|R|', 'Liu|Ping|P|', 'Luo|Shu|S|', 'Zhang|Xiangyang|X|']
D000293:Adolescent D000328:Adult D000368:Aged D001007:Anxiety D002681:China D015331:Cohort Studies D055866:Earthquakes D005260:Female D059647:Gene-Environment Interaction D006801:Humans D007030:Hypothalamo-Hypophyseal System D008297:Male D008875:Middle Aged D010913:Pituitary-Adrenal System D020641:Polymorphism, Single Nucleotide D013313:Stress Disorders, Post-Traumatic D013315:Stress, Psychological D017741:Survivors D055815:Young Adult
Gene Symptoms Hypothalamic-pituitary-adrenal (HPA) axis Stress response Posttraumatic stress disorder (PTSD)