BRIEF RESEARCH REPORT article
Front. Neurosci.
Sec. Brain Imaging Methods
Volume 19 - 2025 | doi: 10.3389/fnins.2025.1574700
The RELN heterozygous single-nucleotide polymorphism rs362691 increases the prefrontal cortical thickness and modulates systemizing-related autistic tendencies in typically developing children and adolescents
Provisionally accepted
Hiroki Sato1,2*
Mitsunari Abe3*
Hikaru Takeuchi4
Hiroaki Tomita5
Shigeo Kure2Ryuta Kawashima4
Yasuyuki Taki4*- 1School of Medicine, Tohoku University, Sendai, Japan
- 2Department of Pediatrics, School of Medicine, Tohoku University, Sendai, Japan
- 3National Center of Neurology and Psychiatry (Japan), Kodaira, Tokyo, Japan
- 4Institute of Development, Aging and Cancer, School of Medicine, Tohoku University, Sendai, Japan
- 5Department of Psychiatry, Tohoku University Hospital, Sendai, Japan
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Reelin, a glycoprotein crucial for neural circuit development and maturation, has been implicated in prefrontal cortex function and cortical dysplasia. The RELN variant rs362691 (p.Leu997Val) is suggested to increase autism spectrum disorder (ASD) susceptibility. Based on the empathizing–systemizing theory, this study investigated the impact of rs362691 on cortical thickness and autism-related cognitive traits in typically developing children and adolescents. We hypothesized that heterozygous Val/Leu individuals would show greater prefrontal cortical thickness correlating with autistic traits, and explored frontal/temporal thickness differences. Results revealed no significant group differences in empathizing or systemizing scores. However, the Val/Leu group exhibited increased medial prefrontal sulci thickness, which correlated with systemizing traits. No association was found between cortical thickness and empathizing traits across the brain. Increased right superior temporal sulcus thickness was also observed, but without correlation to cognitive traits. These findings suggest that while rs362691 may not directly affect autism-related cognition, it might alter prefrontal morphology linked to systemizing in typical development. Methodological limitations warrant future studies with larger cohorts and standardized measures.
Keywords: reelin, polymorphism, empathizing-systemizing theory, Behavioral trait, Magnetic Resonance Imaging, morphology
Received: 11 Feb 2025; Accepted: 22 May 2025.
Copyright: © 2025 Sato, Abe, Takeuchi, Tomita, Kure, Kawashima and Taki. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Hiroki Sato, School of Medicine, Tohoku University, Sendai, Japan
Mitsunari Abe, National Center of Neurology and Psychiatry (Japan), Kodaira, 187-8551, Tokyo, Japan
Yasuyuki Taki, Institute of Development, Aging and Cancer, School of Medicine, Tohoku University, Sendai, 980-8575, Japan
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