Functional gene polymorphisms in the serotonin system and traumatic life events modulate the neural basis of fear acquisition and extinction.
Functional gene polymorphisms in the serotonin system and traumatic life events modulate the neural basis of fear acquisition and extinction.
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DOI：
10.1371/journal.pone.0044352
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Tabbert K
中科院分区：
文献类型：
--
作者：
Hermann A;Küpper Y;Schmitz A;Walter B;Vaitl D;Hennig J;Stark R;Tabbert K
恐惧的获得和消退是焦虑症的病因和维持的关键机制。此外，它们可能在传达遗传和环境因素对(或多或少)更强的精神病理倾向或韧性的发展的影响方面发挥关键作用。在基于遗传和环境的个体在恐惧、学习和灭绝方面的差异方面，神经生物学方面的见解很少。在这项功能磁共振成像研究中，74名健康受试者被调查。根据5-HTTLPR/rs25531(S+vs.LALA；三等位基因分类)和Tph2(G(-703)T)(T+vs.T-)基因型。本研究旨在探讨遗传因素和创伤生活事件对差异恐惧条件反射学习过程中皮肤电导反应(SCRs)和神经反应(杏仁核、脑岛、背侧前扣带回(DACC)和腹内侧额前皮质(VmPFC))的影响。在5-HTTLPR S等位基因携带者中，恐惧习得的特征是右侧岛叶有更强的后期条件反应和非条件反应。在灭绝期间，创伤生活事件与S等位基因携带者与非携带者杏仁核激活减少有关。此外，与非携带者相比，携带Tph2(G(−703)T)多态且有较多创伤性生活事件的T等位基因携带者在获取期间杏仁核和在灭绝学习期间的vmPFC中的反应性增强。最后，在S和T等位基因携带者中发现了两个反应较高的多态在dACC灭绝过程中的联合作用。结果表明，在5-HTTLPR S等位基因携带者中，岛上条件性和非条件性恐惧反应的表达增加。在灭绝过程中，这两种多态对dACC激活的联合影响可能与长时间的恐惧表达有关。杏仁核和vmPFC激活中的基因与环境的相互作用可能反映了一种神经内表型，将遗传和不利的环境影响转化为对情感性精神病理发展的脆弱性或韧性。
Fear acquisition and extinction are crucial mechanisms in the etiology and maintenance of anxiety disorders. Moreover, they might play a pivotal role in conveying the influence of genetic and environmental factors on the development of a (more or less) stronger proneness for, or resilience against psychopathology. There are only few insights in the neurobiology of genetically and environmentally based individual differences in fear learning and extinction. In this functional magnetic resonance imaging study, 74 healthy subjects were investigated. These were invited according to 5-HTTLPR/rs25531 (S+ vs. LALA; triallelic classification) and TPH2 (G(-703)T) (T+ vs. T-) genotype. The aim was to investigate the influence of genetic factors and traumatic life events on skin conductance responses (SCRs) and neural responses (amygdala, insula, dorsal anterior cingulate cortex (dACC) and ventromedial prefrontal cortex (vmPFC)) during acquisition and extinction learning in a differential fear conditioning paradigm. Fear acquisition was characterized by stronger late conditioned and unconditioned responses in the right insula in 5-HTTLPR S-allele carriers. During extinction traumatic life events were associated with reduced amygdala activation in S-allele carriers vs. non-carriers. Beyond that, T-allele carriers of the TPH2 (G(−703)T) polymorphism with a higher number of traumatic life events showed enhanced responsiveness in the amygdala during acquisition and in the vmPFC during extinction learning compared with non-carriers. Finally, a combined effect of the two polymorphisms with higher responses in S- and T-allele carriers was found in the dACC during extinction. The results indicate an increased expression of conditioned, but also unconditioned fear responses in the insula in 5-HTTLPR S-allele carriers. A combined effect of the two polymorphisms on dACC activation during extinction might be associated with prolonged fear expression. Gene-by-environment interactions in amygdala and vmPFC activation may reflect a neural endophenotype translating genetic and adverse environmental influences into vulnerability for or resilience against developing affective psychopathology.
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