Mercer Kristina B, Orcutt Holly K, Quinn Jeffrey F, Fitzgerald Caitlin A, Conneely Karen N, Barfield Richard T, Gillespie Charles F, Ressler Kerry J
School of Medicine, Emory University, Atlanta, Georgia, USA.
Arch Gen Psychiatry. 2012 Jan;69(1):89-97. doi: 10.1001/archgenpsychiatry.2011.109. Epub 2011 Sep 5.
The serotonin transporter (SLC6A4) has been associated with several stress-related syndromes including posttraumatic stress disorder (PTSD). The ability to detect meaningful associations is largely dependent on reliable measures of preexisting trauma.
To study the association of genetic variants within SLC6A4 with acute and posttraumatic stress symptoms in a civilian cohort with known levels of preexisting trauma and PTSD symptoms collected prior to a shared index traumatic event.
Ongoing longitudinal study.
On February 14, 2008, a lone gunman shot multiple people on the campus of Northern Illinois University in DeKalb, Illinois, killing 5 and wounding 21. As part of an ongoing longitudinal study on that campus, a cohort of female undergraduate students, interviewed prior to the shooting, completed follow-up trauma-related measures including PTSD symptom severity (follow-up survey was launched 17 days postshooting; n = 691). To obtain DNA, salivary samples were collected from a subset of the original study population based on willingness to participate (n = 276).
Two hundred four undergraduate women.
SLC6A4 polymorphisms STin2, 5-HTTLPR, and rs25531 were genotyped in 235 individuals.
We found that although the STin2 variant and 5-HTTLPR alone did not associate with increased PTSD symptoms, rs25531 and the 5-HTTLPR multimarker genotype (combined 5-HTTLPR and rs25531) were associated with significantly increased acute stress disorder symptoms at 2 to 4 weeks postshooting (n = 161; P < .05). This association remained significant when controlling for race and for level of shooting exposure (n = 123; P < .007). The association was most robust with the 5-HTTLPR multimarker genotype and avoidance symptoms (P = .003).
These data suggest that differential function of the serotonin transporter may mediate differential response to a severe trauma. When examined in a relatively homogenous sample with shared trauma and known prior levels of child and adult trauma, the 5-HTTLPR multimarker genotype may serve as a useful predictor of risk for PTSD-related symptoms in the weeks and months following the trauma.
血清素转运体(SLC6A4)与多种应激相关综合征有关,包括创伤后应激障碍(PTSD)。检测有意义关联的能力在很大程度上取决于对既往创伤的可靠测量。
在一个平民队列中,研究SLC6A4基因变异与急性应激症状及创伤后应激症状的关联,该队列具有已知的既往创伤水平,且在共同的索引创伤事件之前收集了PTSD症状。
正在进行的纵向研究。
2008年2月14日,一名独行枪手在伊利诺伊州迪卡尔布的北伊利诺伊大学校园开枪射击多人,造成5人死亡,21人受伤。作为该校园正在进行的纵向研究的一部分,一组在枪击事件前接受访谈的本科女生完成了后续与创伤相关的测量,包括PTSD症状严重程度(在枪击事件发生后17天启动后续调查;n = 691)。为了获取DNA,根据参与意愿从原始研究人群的一个子集中收集唾液样本(n = 276)。
204名本科女生。
对235名个体进行SLC6A4基因多态性STin2、5-HTTLPR和rs25531的基因分型。
我们发现,虽然单独的STin2变异和5-HTTLPR与PTSD症状增加无关,但rs25531和5-HTTLPR多标记基因型(5-HTTLPR和rs25531联合)与枪击事件后2至4周急性应激障碍症状显著增加有关(n = 161;P <.05)。在控制种族和枪击暴露水平后,这种关联仍然显著(n = 123;P <.007)。这种关联在5-HTTLPR多标记基因型和回避症状方面最为显著(P =.003)。
这些数据表明,血清素转运体的不同功能可能介导对严重创伤的不同反应。在一个具有共同创伤且儿童和成人创伤既往水平已知的相对同质样本中进行检查时,5-HTTLPR多标记基因型可能作为创伤后数周和数月内PTSD相关症状风险的有用预测指标。