• Akiko Kawamoto, Aiko Kajiume, Hiroshi Yoshida, Tamotsu Toshima, and Masao Kobayashi.
• Department of Pediatrics, Graduate School of Biomedical & Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan. Electronic address: d121709@hiroshima-u.ac.jp.
• Neuroscience. 2021 Mar 15; 458: 43-53.

AbstractAutism 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.Copyright © 2021 IBRO. Published by Elsevier Ltd. All rights reserved.

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