The 5-HTTLPR polymorphism is associated with altered hemodynamic responses during appetitive conditioning
The 5-HTTLPR polymorphism is associated with altered hemodynamic responses during appetitive conditioning
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DOI：
10.1002/hbm.22085
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发表时间：
2013-10-01
影响因子：
4.8
通讯作者：
Stark, Rudolf
中科院分区：
文献类型：
--
作者：
Klucken, Tim;Wehrum, Sina;Stark, Rudolf
背景资料：目前的模型表明，5-羟色胺转运蛋白基因（5-HTTLPR）的启动子区的变异与杏仁核反应性的改变有关，不仅对消极的，而且对积极的刺激，这在过去一直被忽视。这种关联可能会传达出对虐待、渴望和复发等精神病理学的易感性增加。由于食欲条件反射是这些精神疾病的发病机制中的一个重要机制，识别特定的因素，有助于个体间的变化是很重要的。研究方法：在本研究中（N = 86），食欲条件反射范式进行，其中一个中性刺激（CS+）与食欲刺激，而第二个刺激（CS-）预测他们的缺席。根据5-HTTLPR基因型对受试者进行基因分型。结果：作为主要结果，我们报告了5-HTTLPR基因型与血流动力学反应之间的显著相关性。与l/l-等位基因携带者相比，s-等位基因携带者的条件性双侧杏仁核活性升高。此外，s等位基因携带者的血流动力学反应增加也见于扩展的情绪网络，包括眶额皮质、丘脑和腹侧纹状体。结论：5-HTTLPR与食欲条件反射的改变有关。此外，研究结果有助于正在进行的辩论5-HTTLPR依赖的血流动力学反应模式，强调S-等位基因携带者不完全偏向于恐惧，但也对积极的刺激。总之，我们的研究结果意味着，s-等位基因携带者可能更好地描述为对显着刺激的过度反应，这可能会传达精神疾病的发展的脆弱性。《脑地图》34：2549-2560，2013年。(c)2012 Wiley Periodicals，Inc.
Background: Current models suggest that a variation in the promoter region of the serotonin transporter gene (5-HTTLPR) is associated with altered amygdala reactivity not only towards negative but also towards positive stimuli, which has been neglected in the past. This association may possibly convey an elevated vulnerability for psychopathology like abuse, craving, and relapses. Since appetitive conditioning is a crucial mechanism in the pathogenesis of these psychiatric disorders, the identification of specific factors contributing to interindividual variation is important. Methods: In the present study (N = 86), an appetitive conditioning paradigm was conducted, in which a neutral stimulus (CS+) was associated with appetitive stimuli, while a second stimulus (CS-) predicted their absence. Subjects were genotyped according to the 5-HTTLPR genotype. Results: As the main result, we report a significant association between the 5-HTTLPR genotype and hemodynamic responses. Individuals with the s-allele displayed elevated conditioned bilateral amygdala activity in contrast to l/l-allele carriers. Further, increased hemodynamic responses in s-allele carriers were also found in the extended emotional network including the orbitofrontal cortex, the thalamus, and the ventral striatum. Conclusion: The present findings indicate an association of the 5-HTTLPR and altered conditioned responses in appetitive conditioning. Further, the findings contribute to the ongoing debate on 5-HTTLPR dependent hemodynamic response patterns by emphasizing that s-allele carriers are not exclusively biased towards fearful, but also towards positive stimuli. In conclusion, our results imply that s-allele carriers might be better described as hyper-reactive towards salient stimuli, which may convey vulnerability for the development of psychiatric disorders. Hum Brain Mapp 34:2549-2560, 2013. (c) 2012 Wiley Periodicals, Inc.