Department of Medical Imaging, Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, 210002, China.
Imaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, University of Southern California, Marina del Rey, CA, 90292, USA.
Transl Psychiatry. 2020 Jan 30;10(1):46. doi: 10.1038/s41398-020-0728-7.
Losing one's only child is a major traumatic life event that may lead to posttraumatic stress disorder (PTSD); however, not all parents who experience this trauma develop PTSD. Genetic variants are associated with the risk of developing PTSD. Catechol-O-methyltransferase (COMT) rs4680 and brain-derived neurotrophic factor (BDNF) rs6265 are two most well-described single-nucleotide polymorphisms that relate to stress response; however, the neural mechanism underlying their effects on adults who lost an only child remains poorly understood. Two hundred and ten Han Chinese adults who had lost their only child (55 with PTSD and 155 without PTSD) were included in this imaging genetics study. Participants were divided into subgroups according to their COMT rs4680 and BDNF rs6265 genotypes. Degree Centrality (DC)-a resting-state fMRI index reflecting the brain network communication-was compared with a three-way (PTSD diagnosis, COMT, and BDNF polymorphisms) analysis of covariance. Diagnosis state had a significant effect on DC in bilateral inferior parietal lobules and right middle frontal gyrus (MFG), where PTSD adults showed weaker DC. BDNF × diagnosis interaction effect was found in the right MFG and hippocampus, and these two regions were reversely modulated. Also, there was a significant COMT × BDNF interaction effect in left cuneus, middle temporal gyrus, right inferior occipital gyrus, and bilateral putamen, independent of PTSD diagnosis. These findings suggest that the modulatory effect of BDNF polymorphism on the MFG and hippocampus may contribute to PTSD development in bereaved adults. Interactions of COMT × BDNF polymorphisms modulate some cortices and basal ganglia, irrespective of PTSD development.
失去独生子是一个重大的创伤性生活事件，可能导致创伤后应激障碍（PTSD）；然而，并非所有经历这种创伤的父母都会患上 PTSD。遗传变异与 PTSD 的发病风险有关。儿茶酚-O-甲基转移酶（COMT）rs4680 和脑源性神经营养因子（BDNF）rs6265 是两个最著名的与应激反应相关的单核苷酸多态性；然而，它们对失去独生子的成年人的影响的神经机制仍知之甚少。这项影像学遗传学研究纳入了 210 名汉族成年人，他们失去了独生子（55 名患有 PTSD，155 名没有 PTSD）。参与者根据 COMT rs4680 和 BDNF rs6265 基因型分为亚组。静息态功能磁共振成像的度中心度（DC）——反映脑网络通讯的指标——与 PTSD 诊断、COMT 和 BDNF 多态性的三向协方差分析进行了比较。诊断状态对双侧顶下小叶和右侧额中回的 DC 有显著影响，PTSD 组的 DC 较弱。BDNF×诊断的交互作用在右侧额中回和海马体中被发现，这两个区域被反向调节。此外，在左侧楔前叶、颞中回、右侧枕下回和双侧壳核中也发现了 COMT×BDNF 交互作用，与 PTSD 诊断无关。这些发现表明，BDNF 多态性对 MFG 和海马体的调节作用可能导致丧亲成年人 PTSD 的发生。COMT×BDNF 多态性的相互作用调节了一些皮质和基底节，与 PTSD 的发生无关。
