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Individual Differences in Autistic Traits are Associated with Serotonin Transporter Gene Polymorphism Through Medial Prefrontal Function: A Study Using NIRS
Neuroscience ( IF 2.9 ) Pub Date : 2021-01-16 , DOI: 10.1016/j.neuroscience.2021.01.007
Akiko Kawamoto , Aiko Kajiume , Hiroshi Yoshida , Tamotsu Toshima , Masao Kobayashi

Autism spectrum disorder (ASD) is a heritable neurodevelopmental disorder that can vary considerably in severity. Autistic traits are distributed continuously across populations, even in sub-clinical individuals. Serotonin transporter-gene polymorphic region (5-HTTLPR) has been studied as a candidate genetic factor related to ASD, however results have been inconsistent. 5-HTTLPR is implicated in the function of medial prefrontal cortex (mPFC), a region associated with the social abnormalities found in ASD. Here we hypothesize that autistic traits are affected by the 5-HTTLPR genotype indirectly through mPFC mediation. Using near-infrared spectroscopy (NIRS), we first examined mPFC activation in people with ASD when they performed a facial affect-labeling task. Compared with a typical development group, the ASD group showed significantly lower mPFC activation during the task. Using the same task paradigm, we next investigated the relationship between autistic traits and 5-HTTLPR in sub-clinical participants, and whether associations were mediated by mPFC function. Correlation analyses indicated that participants with a large number of 5-HTTLPR L-alleles had high-level autistic traits related to social skills and low right mPFC activation. We also observed a significant negative correlation between autistic traits related to social skills and right mPFC activation. Structural equation analysis suggested a significant indirect effect of 5-HTTLPR on Autism-Spectrum Quotients, with right mPFC activation acting as a mediator. These results suggest that the diverse autistic traits related to social skills seen in the general population are associated with the 5-HTTLPR genotype, and that this association is mediated by right mPFC function.



中文翻译:

自闭症特征的个体差异与通过内侧前额叶功能的5-羟色胺转运蛋白基因多态性相关:一项使用NIRS的研究

自闭症谱系障碍(ASD)是一种遗传性神经发育障碍,严重程度可能有很大差异。自闭症特征在人群中甚至在亚临床个体中也持续分布。已研究了5-羟色胺转运蛋白基因多态性区域(5-HTTLPR)作为与ASD相关的候选遗传因素,但结果不一致。5-HTTLPR与内侧前额叶皮层(mPFC)的功能有关,该区域与ASD中发现的社交异常有关。在这里,我们假设自闭症特征受mPFC介导间接受5-HTTLPR基因型影响。使用近红外光谱(NIRS),我们首先检查了执行面部情感标记任务的ASD患者中mPFC的激活。与典型的开发小组相比,在任务期间,ASD组的mPFC激活明显降低。接下来,我们使用相同的任务范式研究亚临床参与者中自闭症特征与5-HTTLPR之间的关系,以及关联是否由mPFC功能介导。相关分析表明,具有大量5-HTTLPR L等位基因的参与者具有与社交技能和低水平的mPFC激活相关的高级自闭症特征。我们还观察到与社交技能有关的自闭特征与正确的mPFC激活之间存在显着的负相关。结构方程分析表明5-HTTLPR对自闭症频谱商有显着的间接影响,而正确的mPFC激活起中介作用。

更新日期:2021-02-07
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