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The serotonin transporter promoter variant (5-HTTLPR), stress, and depression meta-analysis revisited: evidence of genetic moderation.血清素转运体启动子变体(5-HTTLPR)、压力与抑郁的元分析再探讨:基因调节的证据
Arch Gen Psychiatry. 2011 May;68(5):444-54. doi: 10.1001/archgenpsychiatry.2010.189. Epub 2011 Jan 3.
2
Association of serotonin and dopamine gene pathways with behavioral subphenotypes in dementia.与痴呆行为亚型相关的血清素和多巴胺基因途径。
Neurobiol Aging. 2012 Apr;33(4):791-803. doi: 10.1016/j.neurobiolaging.2010.06.011. Epub 2010 Aug 3.
3
STin2 VNTR polymorphism in the serotonin transporter gene and migraine: pooled and meta-analyses.5-羟色胺转运体基因(STin2)VNTR 多态性与偏头痛:荟萃分析和汇总分析。
J Headache Pain. 2010 Aug;11(4):317-26. doi: 10.1007/s10194-010-0230-3. Epub 2010 Jun 29.
4
Genetics of post-traumatic stress disorder: review and recommendations for genome-wide association studies.创伤后应激障碍的遗传学:全基因组关联研究的综述及建议。
Curr Psychiatry Rep. 2010 Aug;12(4):313-26. doi: 10.1007/s11920-010-0126-6.
5
Preliminary evidence of the short allele of the serotonin transporter gene predicting poor response to cognitive behavior therapy in posttraumatic stress disorder.初步证据表明,5-羟色胺转运体基因的短等位基因可预测创伤后应激障碍患者对认知行为疗法的反应不佳。
Biol Psychiatry. 2010 Jun 15;67(12):1217-9. doi: 10.1016/j.biopsych.2010.03.016.
6
Interactions between functional serotonergic polymorphisms and demographic factors influence personality traits in healthy Spanish Caucasians.功能性血清素多态性与人口统计学因素之间的相互作用影响健康西班牙白种人的人格特质。
Psychiatr Genet. 2010 Aug;20(4):171-8. doi: 10.1097/YPG.0b013e32833a20b9.
7
Genetic sensitivity to the environment: the case of the serotonin transporter gene and its implications for studying complex diseases and traits.遗传对环境的敏感性:以血清素转运体基因为例,及其对研究复杂疾病和特征的意义。
Am J Psychiatry. 2010 May;167(5):509-27. doi: 10.1176/appi.ajp.2010.09101452. Epub 2010 Mar 15.
8
Anxiety sensitivity and posttrauma stress symptoms in female undergraduates following a campus shooting.校园枪击事件后女大学生的焦虑敏感与创伤后应激症状。
J Trauma Stress. 2009 Dec;22(6):489-96. doi: 10.1002/jts.20457.
9
A prospective study of serotonin transporter gene promoter (5-HTT gene linked polymorphic region) and intron 2 (variable number of tandem repeats) polymorphisms as predictors of trauma response to mild physical injury.一项关于 5-羟色胺转运体基因启动子(5-HTT 基因连接多态区)和内含子 2(串联重复数可变)多态性作为轻度躯体损伤创伤反应预测因子的前瞻性研究。
DNA Cell Biol. 2010 Feb;29(2):71-7. doi: 10.1089/dna.2009.0936.
10
Combinatorial interaction between two human serotonin transporter gene variable number tandem repeats and their regulation by CTCF.两个人类血清素转运体基因可变数串联重复序列的组合相互作用及其受 CTCF 的调控。
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一项大学校园枪击事件前瞻性基因与环境研究中的急性和创伤后应激症状

Acute and posttraumatic stress symptoms in a prospective gene x environment study of a university campus shooting.

作者信息

Mercer Kristina B, Orcutt Holly K, Quinn Jeffrey F, Fitzgerald Caitlin A, Conneely Karen N, Barfield Richard T, Gillespie Charles F, Ressler Kerry J

机构信息

School of Medicine, Emory University, Atlanta, Georgia, USA.

出版信息

Arch Gen Psychiatry. 2012 Jan;69(1):89-97. doi: 10.1001/archgenpsychiatry.2011.109. Epub 2011 Sep 5.

DOI:10.1001/archgenpsychiatry.2011.109
PMID:21893641
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3738299/
Abstract

CONTEXT

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.

OBJECTIVE

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.

DESIGN

Ongoing longitudinal study.

SETTING

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).

PARTICIPANTS

Two hundred four undergraduate women.

MAIN OUTCOME MEASURES

SLC6A4 polymorphisms STin2, 5-HTTLPR, and rs25531 were genotyped in 235 individuals.

RESULTS

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).

CONCLUSION

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.

摘要

背景

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。

目的

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。

设计

正在进行的纵向研究。

背景

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)。

参与者

204名本科女生。

主要观察指标

对235名个体进行SLC6A4基因多态性STin2、5-HTTLPR和rs25531的基因分型。

结果

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)。

结论

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。