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.

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。