Human fear acquisition deficits in relation to genetic variants of the corticotropin releasing hormone receptor 1 and the serotonin transporter.
Human fear acquisition deficits in relation to genetic variants of the corticotropin releasing hormone receptor 1 and the serotonin transporter.
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DOI：
10.1371/journal.pone.0063772
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Baas JM
中科院分区：
文献类型：
--
作者：
Heitland I;Groenink L;Bijlsma EY;Oosting RS;Baas JM
识别厌恶事件的预测因子的能力使生物体能够对这些事件做出适当的反应，而无法获得这些恐惧事件可能导致适应不良的情境焦虑。最近，临床前研究表明，促肾上腺皮质激素释放因子和5-羟色胺系统交互参与适应性恐惧获得。在这里，150名健康的无药物人类受试者在虚拟现实环境中完成了提示和上下文恐惧条件反射程序。测量眨眼惊吓反射（FPS）的恐惧增强，以评估无指示的恐惧获得和指示的恐惧表达。所有参与者均进行了位于促肾上腺皮质激素释放激素受体1（CRHR 1-rs 878886）和5-羟色胺转运蛋白（5 HTTLPR）调控区内的多态性基因分型。这些多态性以前分别与恐慌症和焦虑症和人格有关。CRHR 1（rs 878886）的G等位基因携带者在未受指导的阶段没有对威胁线索的恐惧条件反应（FPS）的获得，而恐惧获得存在于C/C纯合子中。此外，携带rs 878886（G等位基因）和5 HTTLPR（短等位基因）的风险等位基因与在此阶段期间对威胁环境的FPS增加相关。在给出关于威胁偶然性的明确指示后，所有基因型组中的提示FPS和背景FPS标准化。目前的研究结果表明，在促肾上腺皮质激素释放激素受体1的遗传变异，特别是在与5 HTTLPR的相互作用，参与了人类的恐惧收购。这将先前的动物发现转化为人类领域。
The ability to identify predictors of aversive events allows organisms to appropriately respond to these events, and failure to acquire these fear contingencies can lead to maladaptive contextual anxiety. Recently, preclinical studies demonstrated that the corticotropin-releasing factor and serotonin systems are interactively involved in adaptive fear acquisition. Here, 150 healthy medication-free human subjects completed a cue and context fear conditioning procedure in a virtual reality environment. Fear potentiation of the eyeblink startle reflex (FPS) was measured to assess both uninstructed fear acquisition and instructed fear expression. All participants were genotyped for polymorphisms located within regulatory regions of the corticotropin releasing hormone receptor 1 (CRHR1 - rs878886) and the serotonin transporter (5HTTLPR). These polymorphisms have previously been linked to panic disorder and anxious symptomology and personality, respectively. G-allele carriers of CRHR1 (rs878886) showed no acquisition of fear conditioned responses (FPS) to the threat cue in the uninstructed phase, whereas fear acquisition was present in C/C homozygotes. Moreover, carrying the risk alleles of both rs878886 (G-allele) and 5HTTLPR (short allele) was associated with increased FPS to the threat context during this phase. After explicit instructions regarding the threat contingency were given, the cue FPS and context FPS normalized in all genotype groups. The present results indicate that genetic variability in the corticotropin-releasing hormone receptor 1, especially in interaction with the 5HTTLPR, is involved in the acquisition of fear in humans. This translates prior animal findings to the human realm.
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人类大麻素受体中未能消除恐惧和遗传变异性1。
影响因子：
6.8
作者：
Heitland I;Klumpers F;Oosting RS;Evers DJ;Leon Kenemans J;Baas JM
通讯作者：
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影响因子：
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作者：
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DOI：
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发表时间：
2009-04-01
影响因子：
4.8
作者：
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通讯作者：
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影响因子：
5.2
作者：
Hauger RL;Risbrough V;Oakley RH;Olivares-Reyes JA;Dautzenberg FM
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