title: Sex-different abnormalities in the right second to fourth digit ratio in Japanese individuals with autism spectrum disorders.
abstract: BACKGROUND
  The prevalence of autism spectrum disorders (ASDs) is higher in men than in women. The extreme male brain theory proposes that excessive prenatal testosterone activity could be a risk factor for ASDs. However, it is unclear whether prenatal sex hormone activity is a risk factor for women. The ratio of the length of the second to fourth digits (2D:4D) is considered to be a biomarker of the prenatal ratio of testosterone to estrogen. Therefore, this study compared the 2D:4D ratios of women with and without ASDs to determine if prenatal sex hormone activity could be a risk factor for ASDs in women.
  
  
  METHODS
  The study included 35 Japanese men with ASDs, 17 Japanese women with ASDs, 59 typically developed (TD) Japanese men, and 57 TD Japanese women. We measured digit lengths and compared the 2D:4D ratios among the four groups. We also examined the relationship between the 2D:4D ratio and the autism-spectrum quotient score of each group.
  
  
  RESULTS
  In our cohort, men with ASDs tended to have lower right-hand 2D:4D ratios relative to TD men. In contrast, the right 2D:4D ratios in women with ASDs were higher compared to those of TD women. No significant correlations were found between the 2D:4D ratios and the autism-spectrum quotient scores in any group. The higher right 2D:4D ratios in women could not be explained by age or full-scale intelligent quotients. This group difference was not found for the left 2D:4D or right-left 2D:4D ratios.
  
  
  CONCLUSIONS
  We found a reverse direction of abnormality in the right 2D:4D ratio for men and women with ASDs. It has been posited that high prenatal testosterone levels lead to a lower 2D:4D ratio. However, a recent animal study showed that testosterone injection to dam leads to a higher right 2D:4D ratio especially for female offspring, which might be mediated by abnormal adipose accumulation in the fingertip. Therefore, the present findings suggest that high prenatal testosterone could be a risk factor both for Japanese men and women with ASDs, elucidating one potential etiology of ASDs in women.
authors.affiliation: Department of Neuropsychiatry, Faculty of Medical Sciences, University of Fukui, Fukui, 910-1193 Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Masuya
authors.affiliation: Research Center for Child Mental Development, University of Fukui, Fukui, 910-1193 Japan ; Division of Developmental Higher Brain Functions, Department of Child Development, United Graduate School of Child Development, Osaka University, Kanazawa University, Hamamatsu University School of Medicine, Chiba University and University of Fukui, Fukui, 910-1193 Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Okamoto
authors.affiliation: Department of Neuropsychiatry, Faculty of Medical Sciences, University of Fukui, Fukui, 910-1193 Japan ; Department of Informatics, Graduate School of Informatics and Engineering, The University of Electro-Communications, Chofu, 182-8585 Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Inohara
authors.affiliation: Department of Neuropsychiatry, Faculty of Medical Sciences, University of Fukui, Fukui, 910-1193 Japan.
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Matsumura
authors.affiliation: Department of Neuropsychiatry, Faculty of Medical Sciences, University of Fukui, Fukui, 910-1193 Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Fujioka
authors.affiliation: Department of Neuropsychiatry, Faculty of Medical Sciences, University of Fukui, Fukui, 910-1193 Japan ; Research Center for Child Mental Development, University of Fukui, Fukui, 910-1193 Japan ; Division of Developmental Higher Brain Functions, Department of Child Development, United Graduate School of Child Development, Osaka University, Kanazawa University, Hamamatsu University School of Medicine, Chiba University and University of Fukui, Fukui, 910-1193 Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Wada
authors.affiliation: Department of Neuropsychiatry, Faculty of Medical Sciences, University of Fukui, Fukui, 910-1193 Japan ; Research Center for Child Mental Development, University of Fukui, Fukui, 910-1193 Japan ; Division of Developmental Higher Brain Functions, Department of Child Development, United Graduate School of Child Development, Osaka University, Kanazawa University, Hamamatsu University School of Medicine, Chiba University and University of Fukui, Fukui, 910-1193 Japan.
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Kosaka
keywords: Autism spectrum disorders; Digit ratio; Etiology; Prenatal estrogen; Prenatal testosterone; Sex difference