The cortical surface area of the insula mediates the effect of DBH rs7040170 on novelty seeking
The cortical surface area of the insula mediates the effect of DBH rs7040170 on novelty seeking
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DOI：
10.1016/j.neuroimage.2015.05.033
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发表时间：
2015-08
期刊：
影响因子：
5.7
通讯作者：
Jin Li;Yue Cui;Karen Wu;Bing Liu;Yun Zhang;Chao Wang-;T. Jiang
中科院分区：
文献类型：
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作者：
Jin Li;Yue Cui;Karen Wu;Bing Liu;Yun Zhang;Chao Wang-;T. Jiang
新奇寻求（NS）是一种对适应功能很重要的人格特质，但过度的NS水平与精神疾病如ADHD和药物滥用有关。以前的研究分别调查了NS性状的神经和遗传基础，但结果是混合的，神经和遗传基础尚未在同一研究中进行检查。在这项研究中，我们研究了多巴胺β-羟化酶（DBH）基因，脑结构和NS性状之间的相互关系，在359名健康的中国汉族受试者。我们关注DBH基因，因为它编码多巴胺代谢的关键酶，NS被认为与多巴胺能系统有关，并已报道与DBH变异有关。结果显示，左侧大脑皮层表面积与NS评分之间存在显著正相关。此外，在SNP rs7040170的DBH遗传多态性与左心室表面积和NS评分密切相关，与AA纯合子相比，G携带者具有更大的左心室表面积和更高的NS评分。随后的通径分析表明，DBH基因部分介导了NS性状与DBH基因的关联。我们的数据提供了第一个证据表明多巴胺-NS关系中的多巴胺受体参与。未来的研究NS人格特质和相关的精神疾病的分子机制应考虑神经结构的中介作用。
Novelty seeking (NS) is a personality trait important for adaptive functioning, but an excessive level of NS has been linked to psychiatric disorders such as ADHD and substance abuse. Previous research has investigated separately the neural and genetic bases of the NS trait, but results were mixed and neural and genetic bases have yet to be examined within the same study. In this study, we examined the interrelationships among the dopamine beta-hydroxylase (DBH) gene, brain structure, and the NS trait in 359 healthy Han Chinese subjects. We focused on theDBHgene because it encodes a key enzyme for dopamine metabolism, NS is believed to be related to the dopaminergic system and has been reported associated withDBHvariation. Results showed a significant positive association between the cortical surface area of the left insula and NS score. Furthermore, theDBHgenetic polymorphism at the SNP rs7040170 was strongly associated with both the surface area of the left insula and NS score, with G carriers having a larger left insula surface area and a higher NS score than AA homozygotes. Subsequent path analysis suggested that the insula partially mediated the association between theDBHgene and the NS trait. Our data provided the first evidence for the involvement of the insula in the dopamine–NS relationship. Future studies of molecular mechanisms underlying the NS personality trait and related psychiatric disorders should consider the mediation effect of the neural structure.