Neural correlate of autistic-like traits and a common allele in the oxytocin receptor gene.
Sub-clinical autistic-like traits (ALTs) are continuously distributed in the general population and genetically linked to autism. Although identifying the neurogenetic backgrounds of ALTs might enhance our ability to identify those of autism, they are largely unstudied. Here, we have examined the neuroanatomical basis of ALTs and their association with the oxytocin receptor gene (OXTR) rs2254298A, a known risk allele for autism in Asian populations which has also been implicated in limbic-paralimbic brain structures. First, we extracted a four-factor structure of ALTs, as measured using the Autism-Spectrum Quotient, including 'prosociality', 'communication', 'details/patterns' and 'imagination' in 135 neurotypical adults (79 men, 56 women) to reduce the genetic heterogeneity of ALTs. Then, in the same population, voxel-based morphometry revealed that lower 'prosociality', which indicates strong ALTs, was significantly correlated to smaller regional grey matter volume in the right insula in males. Males with lower 'prosociality' also had less interregional structural coupling between the right insula and the ventral anterior cingulate cortex. Furthermore, males with OXTR rs2254298A had significantly smaller grey matter volume in the right insula. These results show that decreased volume of the insula is a neuroanatomical correlate of ALTs and a potential intermediate phenotype linking ALTs with OXTR in male subjects.
Department of Neuropsychiatry, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan, Department of Radiology, Nihon University School of Medicine, 30-1 Oyaguchi kami-cho, Itabashi-ku, Tokyo 173-8610, Japan, Global Center of Excellence (COE) Program, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan, Department of Child Psychiatry, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan, Department of Human Genetics, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan, Health Service Center, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan, and Japan Science and Technology Agency, CREST, 5 Sanbancho, Chiyoda-ku, Tokyo 102-0075, Japan.
Yuki
Y
Saito
Department of Neuropsychiatry, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan, Department of Radiology, Nihon University School of Medicine, 30-1 Oyaguchi kami-cho, Itabashi-ku, Tokyo 173-8610, Japan, Global Center of Excellence (COE) Program, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan, Department of Child Psychiatry, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan, Department of Human Genetics, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan, Health Service Center, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan, and Japan Science and Technology Agency, CREST, 5 Sanbancho, Chiyoda-ku, Tokyo 102-0075, Japan.
Motomu
M
Suga
Department of Neuropsychiatry, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan, Department of Radiology, Nihon University School of Medicine, 30-1 Oyaguchi kami-cho, Itabashi-ku, Tokyo 173-8610, Japan, Global Center of Excellence (COE) Program, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan, Department of Child Psychiatry, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan, Department of Human Genetics, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan, Health Service Center, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan, and Japan Science and Technology Agency, CREST, 5 Sanbancho, Chiyoda-ku, Tokyo 102-0075, Japan.
Mamoru
M
Tochigi
Department of Neuropsychiatry, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan, Department of Radiology, Nihon University School of Medicine, 30-1 Oyaguchi kami-cho, Itabashi-ku, Tokyo 173-8610, Japan, Global Center of Excellence (COE) Program, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan, Department of Child Psychiatry, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan, Department of Human Genetics, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan, Health Service Center, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan, and Japan Science and Technology Agency, CREST, 5 Sanbancho, Chiyoda-ku, Tokyo 102-0075, Japan.
Osamu
O
Abe
Department of Neuropsychiatry, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan, Department of Radiology, Nihon University School of Medicine, 30-1 Oyaguchi kami-cho, Itabashi-ku, Tokyo 173-8610, Japan, Global Center of Excellence (COE) Program, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan, Department of Child Psychiatry, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan, Department of Human Genetics, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan, Health Service Center, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan, and Japan Science and Technology Agency, CREST, 5 Sanbancho, Chiyoda-ku, Tokyo 102-0075, Japan Department of Neuropsychiatry, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan, Department of Radiology, Nihon University School of Medicine, 30-1 Oyaguchi kami-cho, Itabashi-ku, Tokyo 173-8610, Japan, Global Center of Excellence (COE) Program, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan, Department of Child Psychiatry, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan, Department of Human Genetics, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan, Health Service Center, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan, and Japan Science and Technology Agency, CREST, 5 Sanbancho, Chiyoda-ku, Tokyo 102-0075, Japan.
Noriaki
N
Yahata
Department of Neuropsychiatry, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan, Department of Radiology, Nihon University School of Medicine, 30-1 Oyaguchi kami-cho, Itabashi-ku, Tokyo 173-8610, Japan, Global Center of Excellence (COE) Program, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan, Department of Child Psychiatry, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan, Department of Human Genetics, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan, Health Service Center, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan, and Japan Science and Technology Agency, CREST, 5 Sanbancho, Chiyoda-ku, Tokyo 102-0075, Japan.
Yuki
Y
Kawakubo
Department of Neuropsychiatry, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan, Department of Radiology, Nihon University School of Medicine, 30-1 Oyaguchi kami-cho, Itabashi-ku, Tokyo 173-8610, Japan, Global Center of Excellence (COE) Program, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan, Department of Child Psychiatry, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan, Department of Human Genetics, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan, Health Service Center, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan, and Japan Science and Technology Agency, CREST, 5 Sanbancho, Chiyoda-ku, Tokyo 102-0075, Japan.
Xiaoxi
X
Liu
Department of Neuropsychiatry, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan, Department of Radiology, Nihon University School of Medicine, 30-1 Oyaguchi kami-cho, Itabashi-ku, Tokyo 173-8610, Japan, Global Center of Excellence (COE) Program, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan, Department of Child Psychiatry, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan, Department of Human Genetics, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan, Health Service Center, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan, and Japan Science and Technology Agency, CREST, 5 Sanbancho, Chiyoda-ku, Tokyo 102-0075, Japan.
Yoshiya
Y
Kawamura
Department of Neuropsychiatry, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan, Department of Radiology, Nihon University School of Medicine, 30-1 Oyaguchi kami-cho, Itabashi-ku, Tokyo 173-8610, Japan, Global Center of Excellence (COE) Program, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan, Department of Child Psychiatry, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan, Department of Human Genetics, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan, Health Service Center, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan, and Japan Science and Technology Agency, CREST, 5 Sanbancho, Chiyoda-ku, Tokyo 102-0075, Japan.
Tsukasa
T
Sasaki
Department of Neuropsychiatry, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan, Department of Radiology, Nihon University School of Medicine, 30-1 Oyaguchi kami-cho, Itabashi-ku, Tokyo 173-8610, Japan, Global Center of Excellence (COE) Program, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan, Department of Child Psychiatry, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan, Department of Human Genetics, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan, Health Service Center, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan, and Japan Science and Technology Agency, CREST, 5 Sanbancho, Chiyoda-ku, Tokyo 102-0075, Japan.
Kiyoto
K
Kasai
Department of Neuropsychiatry, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan, Department of Radiology, Nihon University School of Medicine, 30-1 Oyaguchi kami-cho, Itabashi-ku, Tokyo 173-8610, Japan, Global Center of Excellence (COE) Program, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan, Department of Child Psychiatry, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan, Department of Human Genetics, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan, Health Service Center, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan, and Japan Science and Technology Agency, CREST, 5 Sanbancho, Chiyoda-ku, Tokyo 102-0075, Japan Department of Neuropsychiatry, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan, Department of Radiology, Nihon University School of Medicine, 30-1 Oyaguchi kami-cho, Itabashi-ku, Tokyo 173-8610, Japan, Global Center of Excellence (COE) Program, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan, Department of Child Psychiatry, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan, Department of Human Genetics, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan, Health Service Center, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan, and Japan Science and Technology Agency, CREST, 5 Sanbancho, Chiyoda-ku, Tokyo 102-0075, Japan yamasue-tky@umin.ac.jp.
Hidenori
H
Yamasue
D000328:Adult; D001321:Autistic Disorder / Q000235:genetics* / Q000473:pathology*; D001931:Brain Mapping; D002540:Cerebral Cortex / Q000473:pathology*; D005163:Factor Analysis, Statistical; D005260:Female; D007839:Functional Laterality / Q000235:genetics; D056726:Genetic Association Studies; D005838:Genotype; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D018045:Receptors, Oxytocin / Q000235:genetics*; D012727:Sex Characteristics; D055815:Young Adult
C569600:OXTR protein, human; D018045:Receptors, Oxytocin
asperger; endophenotype; imaging genetics; pervasive developmental disorder; sex difference