title: White matter microstructure in a genetically defined group at increased risk of autism symptoms, and a comparison with idiopathic autism: an exploratory study.
abstract: Klinefelter syndrome (47,XXY) is associated with physical, behavioral, and cognitive consequences. Deviations in brain structure and function have been reported, but structural characteristics of white matter have barely been assessed. This exploratory diffusion tensor imaging study assessed white matter microstructure in boys with 47,XXY compared with non-clinical, male controls. Additionally, both similarities and differences between 47,XXY and autism spectrum disorders (ASD) have been reported in cognition, behavior and neural architecture. To further investigate these brain-behavior pathways, white matter microstructure in boys with 47,XXY was compared to that of boys with ASD. Fractional anisotropy (FA), radial diffusivity (Dr), axial diffusivity (Da), and mean diffusivity (MD) were assessed in 47,XXY (n = 9), ASD (n = 18), and controls (n = 14), using tract-based spatial statistics. Compared with controls, boys with 47,XXY have reduced FA, coupled with reduced Da, in the corpus callosum. Boys with 47,XXY also have reduced Dr. in the left anterior corona radiata and sagittal striatum compared with controls. Compared with boys with ASD, boys with 47,XXY show reduced Da in the right inferior fronto-occipital fasciculus. Although this study is preliminary considering the small sample size, reduced white matter integrity in the corpus callosum may be a contributing factor in the cognitive and behavioral problems associated with 47,XXY. In addition, the differences in white matter microstructure between 47,XXY and ASD may be important for our understanding of the mechanisms that are fundamental to behavioral outcome in social dysfunction, and may be targeted through intervention.
authors.affiliation: Faculty of Social and Behavioural Sciences, Department of Clinical Child and Adolescent Studies, Leiden University, Wassenaarseweg 52, 2333 AK, Leiden, The Netherlands. m.n.goddard@fsw.leidenuniv.nl.|Leiden Institute for Brain and Cognition, Leiden, The Netherlands. m.n.goddard@fsw.leidenuniv.nl.
authors.forename: Marcia N
authors.initials: MN
authors.lastname: Goddard
authors.affiliation: Faculty of Social and Behavioural Sciences, Department of Clinical Child and Adolescent Studies, Leiden University, Wassenaarseweg 52, 2333 AK, Leiden, The Netherlands.|Leiden Institute for Brain and Cognition, Leiden, The Netherlands.
authors.forename: Sophie
authors.initials: S
authors.lastname: van Rijn
authors.affiliation: Institute of Psychology, Leiden University, Leiden, The Netherlands.|Leiden Institute for Brain and Cognition, Leiden, The Netherlands.|Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Serge A R B
authors.initials: SA
authors.lastname: Rombouts
authors.affiliation: Faculty of Social and Behavioural Sciences, Department of Clinical Child and Adolescent Studies, Leiden University, Wassenaarseweg 52, 2333 AK, Leiden, The Netherlands.|Leiden Institute for Brain and Cognition, Leiden, The Netherlands.
authors.forename: Hanna
authors.initials: H
authors.lastname: Swaab
mesh_terms: D000293:Adolescent; D000704:Analysis of Variance; D001321:Autistic Disorder / Q000000981:diagnostic imaging* / Q000235:genetics*; D002648:Child; D056324:Diffusion Tensor Imaging; D020022:Genetic Predisposition to Disease; D006801:Humans; D007360:Intelligence; D007361:Intelligence Tests; D007713:Klinefelter Syndrome / Q000000981:diagnostic imaging* / Q000235:genetics* / Q000523:psychology; D008279:Magnetic Resonance Imaging; D008297:Male; D011569:Psychiatric Status Rating Scales; D066127:White Matter / Q000000981:diagnostic imaging*
keywords: Autism; Diffusion tensor imaging; Genetics; Klinefelter syndrome; Structural connectivity; White matter