Departments of Society, Human Development, and Health and Epidemiology, Harvard School of Public Health, Boston, Massachusetts 02115, USA.
Depress Anxiety. 2011 Aug;28(8):639-47. doi: 10.1002/da.20825. Epub 2011 May 23.
Posttraumatic stress disorder (PTSD) is a common and debilitating mental disorder that occurs following exposure to a traumatic event. However, most individuals do not develop PTSD following even a severe trauma, leading to a search for new variables, such as genetic and other molecular variation, associated with vulnerability and resilience in the face of trauma exposure.
We examined whether serotonin transporter (SLC6A4) promoter genotype and methylation status modified the association between number of traumatic events experienced and PTSD in a subset of 100 individuals from the Detroit Neighborhood Health Study.
Number of traumatic events was strongly associated with risk of PTSD. Neither SLC6A4 genotype nor methylation status was associated with PTSD in main effects models. However, SLC6A4 methylation levels modified the effect of the number of traumatic events on PTSD after controlling for SLC6A4 genotype. Persons with more traumatic events were at increased risk for PTSD, but only at lower methylation levels. At higher methylation levels, individuals with more traumatic events were protected from this disorder. This interaction was observed whether the outcome was PTSD diagnosis, symptom severity, or number of symptoms.
Gene-specific methylation patterns may offer potential molecular signatures of increased risk for and resilience to PTSD.
创伤后应激障碍（PTSD）是一种常见且使人衰弱的精神障碍，发生在经历创伤事件之后。然而，即使是在严重创伤之后，大多数人也不会患上 PTSD，这导致人们开始寻找新的变量，如遗传和其他分子变异，这些变量与面对创伤暴露时的脆弱性和弹性有关。
我们研究了在底特律社区健康研究中的 100 名个体的一个子集中，5-羟色胺转运体（SLC6A4）启动子基因型和甲基化状态是否改变了经历的创伤事件数量与 PTSD 之间的关联。
创伤事件的数量与 PTSD 的风险强烈相关。SLC6A4 基因型或甲基化状态在主要效应模型中均与 PTSD 无关。然而，在控制 SLC6A4 基因型后，SLC6A4 甲基化水平改变了创伤事件数量对 PTSD 的影响。经历更多创伤事件的人患 PTSD 的风险增加，但仅在较低的甲基化水平下如此。在较高的甲基化水平下，经历更多创伤事件的个体可以免受这种疾病的影响。无论结局是 PTSD 诊断、症状严重程度还是症状数量，这种相互作用都存在。
基因特异性甲基化模式可能为 PTSD 的风险增加和恢复力提供潜在的分子特征。
