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.
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.
Horm Behav. 2020 Jan;117:104604. doi: 10.1016/j.yhbeh.2019.104604. Epub 2019 Nov 6.
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.
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.
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).
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.
下丘脑-垂体-肾上腺（HPA）轴是控制应激反应的主要神经内分泌系统，包括恐惧学习。为了进一步了解人类 HPA 轴与应激和恐惧相关症状之间的相关性，本研究调查了 HPA 轴基因多态性与应激和恐惧相关障碍创伤后应激障碍（PTSD）之间的关系。这是第一项系统研究 HPA 轴基因与不同 PTSD 症状群之间相关性的研究。
参与者包括 1132 名中国地震幸存者（772 名女性和 360 名男性）。使用 DSM-5 创伤后应激障碍检查表（PCL-5）测量 PTSD 症状，根据 DSM-5 PTSD 的混合七因素模型计算症状的严重程度（总症状）和症状群。我们对三个 HPA 轴基因（FKBP5、CRHR1 和 CRHR2）的 8 个单核苷酸多态性（SNP）进行了基因分型。
CRHR2 基因 SNP rs2267715 的主要效应与 PTSD 严重程度（P=0.0035）和除烦躁觉醒外的所有 PTSD 症状群（P 范围从 0.0011 到 0.048）相关。在女性中，FKBP5（rs3800373×创伤暴露）的基因-环境相互作用（G×E）效应与 PTSD 严重程度（P=0.038）、外化行为、焦虑觉醒和烦躁觉醒症状相关（P 范围从 0.014 到 0.028）；CRHR1（rs4458044×创伤暴露）的 G×E 效应与焦虑觉醒症状相关（P=0.016）。在男性中，FKBP5-CRHR1（rs9470080×rs4458044）的基因-基因相互作用（G×G）效应与 PTSD 严重程度（P=0.0091）、闯入、负性情绪、外化行为和焦虑觉醒相关（P 范围从 0.012 到 0.049）。
我们的研究结果系统地揭示了 HPA 轴基因某些遗传多态性的主要效应以及 G×E 和 G×G 效应与 PTSD 的严重程度和不同的症状群有关。
