Kawamoto Akiko, Kajiume Aiko, Yoshida Hiroshi, Toshima Tamotsu, Kobayashi Masao
Department of Pediatrics, Graduate School of Biomedical & Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan.
Department of Pediatrics, Graduate School of Biomedical & Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan.
Neuroscience. 2021 Mar 15;458:43-53. doi: 10.1016/j.neuroscience.2021.01.007. Epub 2021 Jan 16.
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，其严重程度差异很大。自闭症特征在人群中呈连续分布，即使在亚临床个体中也是如此。血清素转运体基因多态性区域（5-HTTLPR）已被作为与ASD相关的候选遗传因素进行研究，但其结果并不一致。5-HTTLPR与内侧前额叶皮质（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通过mPFC介导间接受到5-HTTLPR基因型的影响。我们首先使用近红外光谱（NIRS）检查了ASD患者在执行面部表情标签任务时mPFC的激活情况。与典型发育组相比，ASD组在任务期间的mPFC激活明显较低。接下来，我们使用相同的任务范式，研究了亚临床参与者的自闭症特征与5-HTTLPR之间的关系，以及这种关联是否由mPFC功能介导。相关分析表明，拥有大量5-HTTLPR L等位基因的参与者具有与社交技能相关的高水平自闭症特征，且右侧mPFC激活较低。我们还观察到与社交技能相关的自闭症特征与右侧mPFC激活之间存在显著负相关。结构方程分析表明，5-HTTLPR对自闭症谱系商数有显著的间接影响，右侧mPFC激活起到了中介作用。这些结果表明，在普通人群中看到的与社交技能相关的各种自闭症特征与5-HTTLPR基因型有关，并且这种关联是由右侧mPFC功能介导的。
