Xu Ling, Zhang Jingyi, Yang Haibo, Cao Chengqi, Fang Ruojiao, Liu Ping, Luo Shu, Wang Binbin, Zhang Kunlin, Wang Li
Laboratory for Traumatic Stress Studies and Center for Genetics and BioMedical Informatics Research, CAS Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing, China.
Department of Psychology, University of Chinese Academy of Sciences, Beijing, China.
Front Psychiatry. 2024 Feb 29;15:1257911. doi: 10.3389/fpsyt.2024.1257911. eCollection 2024.
Posttraumatic stress disorder (PTSD) and major depressive disorder (MDD) comorbidity occurs through exposure to trauma with genetic susceptibility. Neuropeptide-Y (NPY) and dopamine are neurotransmitters associated with anxiety and stress-related psychiatry through receptors. We attempted to explore the genetic association between two neurotransmitter receptor systems and the PTSD-MDD comorbidity.
Four groups were identified using latent profile analysis (LPA) to examine the patterns of PTSD and MDD comorbidity among survivors exposed to earthquake-related trauma: low symptoms, predominantly depression, predominantly PTSD, and PTSD-MDD comorbidity. (rs4425326), (rs11724320), (rs1079597), and (rs6280) were genotyped from 1,140 Chinese participants exposed to earthquake-related trauma. Main, gene-environment interaction (G × E), and gene-gene interaction (G × G) effects for low symptoms, predominantly depression, and predominantly PTSD were tested using a multinomial logistic model with PTSD-MDD comorbidity as a reference.
The results demonstrated that compared to PTSD-MDD comorbidity, epistasis (G × G) - (rs4425326 × rs1079597) affects low symptoms ( = -0.66, = 0.52 [95% CI: 0.32-0.84], = 0.008, = 0.008) and predominantly PTSD ( = -0.56, = 0.57 [95% CI: 0.34-0.97], = 0.037, = 0.039), while - (rs4425326 × rs6280) impacts low symptoms ( = 0.82, = 2.27 [95% CI: 1.26-4.10], = 0.006, = 0.005) and predominantly depression ( = 1.08, = 2.95 [95% CI: 1.55-5.62], = 0.001, = 0.001). The two G × G effects are independent.
NPY and dopamine receptor genes are related to the genetic etiology of PTSD-MDD comorbidity, whose specific mechanisms can be studied at multiple levels.
创伤后应激障碍（PTSD）和重度抑郁症（MDD）共病是通过暴露于具有遗传易感性的创伤而发生的。神经肽Y（NPY）和多巴胺是通过受体与焦虑和应激相关精神疾病相关的神经递质。我们试图探讨两种神经递质受体系统与PTSD-MDD共病之间的遗传关联。
使用潜在剖面分析（LPA）确定四组，以检查暴露于与地震相关创伤的幸存者中PTSD和MDD共病的模式：低症状、以抑郁为主、以PTSD为主以及PTSD-MDD共病。对1140名暴露于与地震相关创伤的中国参与者进行了（rs4425326）、（rs11724320）、（rs1079597）和（rs6280）的基因分型。以PTSD-MDD共病为参照，使用多项逻辑模型测试低症状、以抑郁为主和以PTSD为主的主效应、基因-环境相互作用（G×E）和基因-基因相互作用（G×G）效应。
结果表明，与PTSD-MDD共病相比，上位性（G×G）-（rs4425326×rs1079597）影响低症状（β=-0.66，OR=0.52[95%CI：0.32-0.84]，P=0.008，FDR=0.008）和以PTSD为主的情况（β=-0.56，OR=0.57[95%CI：0.34-0.97]，P=0.037，FDR=0.039），而-（rs4425326×rs6280）影响低症状（β=0.82，OR=2.27[95%CI：1.26-4.10]，P=0.006，FDR=0.005）和以抑郁为主的情况（β=1.08，OR=2.95[95%CI：1.55-5.62]，P=0.001，FDR=0.001）。这两种G×G效应是独立的。
NPY和多巴胺受体基因与PTSD-MDD共病的遗传病因有关，其具体机制可在多个层面进行研究。
