Hu Xian-Zhang, Ursano Robert J, Benedek David, Li Xiaoxia, Zhang Lei
Center for the Study of Traumatic Stress, Department of Psychiatry, USUHS, Bethesda, MD, USA.
Henry M Jackson Foundation for the Advancement of Military Medicine.
Chronic Stress (Thousand Oaks). 2024 Apr 26;8:24705470241245497. doi: 10.1177/24705470241245497. eCollection 2024 Jan-Dec.
Post-traumatic stress disorder (PTSD) is a mental disorder that manifests after exposure to a stressful traumatic event, such as combat experience. Accumulated evidence indicates an important genetic influence in the development of PTSD. The serotonin transporter (5-HTT) gene has been identified as a candidate for PTSD and a polymorphism of the serotonin transporter-linked promoter region (5-HTTLPR) is associated with the disorder in the general population. However, whether it is associated with PTSD in active military service members has not been investigated. This study aimed to investigate the relationship between 5-HTTLPR and PTSD in service members.
Leucocyte genomic DNA was extracted from service members, including those with PTSD (n = 134) or without PTSD (n = 639). The 5-HTTLPR polymorphism was detected by means of 2 stages of TaqMan fluorescent PCR assay. PTSD symptoms and symptom severity were assessed using the PTSD Checklist (PCL), a 17-item, DSM-based, self-report questionnaire with well-established validity and reliability. PTSD was determined based on endorsement of DSM-IV criteria and a PCL total score ≥ 44.
Significant differences in biallele distribution were observed between PTSD and controls (χ2 = 7.497, = .024). The frequency of SS, SL, and LL genotypes in the PTSD group was 0.17, 0.56, and 0.27 respectively, compared to the frequencies of 0.27, 0.43, and 0.29 in non-PTSD controls. Carriers of the L allele had higher scores for reexperiencing and arousal symptoms on the PCL, compared to SS homozygote carriers ( < .05). The triallele genotypes showed no significant differences in distribution between the PTSD and control groups ( > .05) and no relationship with PTSD symptom severity. The interaction of triallelic genotypes of 5-HTTLPR and traumatic life events was associated with re-experiencing, avoidance, and arousal ( < .05 for all). Multiple regression analysis revealed significant correlations between both biallelic and triallelic genotypes of 5-HTTLPR, the interaction of the number of stressful lifetime events, and 5-HTTLPR genotypes with PCL total score ( < .001).
Our findings suggested that 5-HTT might play a minor role in PTSD, and the interaction between 5-HTTLPR and the environment had effects on PCL score, complementing and emphasizing 5-HTT for PTSD, especially in the military population.
创伤后应激障碍(PTSD)是一种在接触如战斗经历等应激性创伤事件后出现的精神障碍。越来越多的证据表明基因在PTSD的发生发展中具有重要影响。血清素转运体(5-HTT)基因已被确定为PTSD的一个候选基因,且血清素转运体相关启动子区域(5-HTTLPR)的多态性与普通人群中的该障碍有关。然而,它是否与现役军人的PTSD相关尚未得到研究。本研究旨在调查军人中5-HTTLPR与PTSD之间的关系。
从军人中提取白细胞基因组DNA,包括患有PTSD的军人(n = 134)和未患PTSD的军人(n = 639)。通过两阶段的TaqMan荧光PCR检测法检测5-HTTLPR多态性。使用PTSD检查表(PCL)评估PTSD症状及症状严重程度,PCL是一份基于《精神疾病诊断与统计手册》的17项自我报告问卷,具有良好的效度和信度。根据认可的《精神疾病诊断与统计手册》第四版标准及PCL总分≥44来确定PTSD。
在PTSD患者与对照组之间观察到双等位基因分布存在显著差异(χ2 = 7.497,P = 0.024)。PTSD组中SS、SL和LL基因型的频率分别为0.17、0.56和0.27,而非PTSD对照组的频率分别为0.27、0.43和0.29。与SS纯合子携带者相比,L等位基因携带者在PCL上的再体验和觉醒症状得分更高(P < 0.05)。三等位基因基因型在PTSD组与对照组之间的分布无显著差异(P > 0.05),且与PTSD症状严重程度无关。5-HTTLPR的三等位基因基因型与创伤性生活事件的相互作用与再体验、回避和觉醒相关(所有P < 0.05)。多元回归分析显示5-HTTLPR的双等位基因和三等位基因基因型、应激性生活事件数量的相互作用以及5-HTTLPR基因型与PCL总分之间均存在显著相关性(P < 0.001)。
我们的研究结果表明5-HTT可能在PTSD中起次要作用,5-HTTLPR与环境之间的相互作用对PCL得分有影响,补充并强调了5-HTT在PTSD中的作用,尤其是在军人人群中。