title: Developmental white matter microstructure in autism phenotype and corresponding endophenotype during adolescence.
abstract: During adolescence, white matter microstructure undergoes an important stage of development. It is hypothesized that the alterations of brain connectivity that have a key role in autism spectrum conditions (ASCs) may interact with the development of white matter microstructure. This interaction may be present beyond the phenotype of autism in siblings of individuals with ASC, who are 10 to 20 times more likely to develop certain forms of ASC. We use diffusion tensor imaging to examine how white matter microstructure measurements correlate with age in typically developing individuals, and how this correlation differs in n=43 adolescents with ASC and their n=38 siblings. Correlations observed in n=40 typically developing individuals match developmental changes noted in previous longitudinal studies. In comparison, individuals with ASC display weaker negative correlation between age and mean diffusivity in a broad area centred in the right superior longitudinal fasciculus. These differences may be caused either by increased heterogeneity in ASC or by temporal alterations in the group's developmental pattern. Siblings of individuals with ASC also show diminished negative correlation between age and one component of mean diffusivity-second diffusion eigenvalue-in the right superior longitudinal fasciculus. As the observed differences match for location and correlation directionality in our comparison of typically developing individuals to those with ASC and their siblings, we propose that these alterations constitute a part of the endophenotype of autism.
authors.affiliation: 1] Brain Mapping Unit, Department of Psychiatry, University of Cambridge, Cambridge, UK [2] Department of Psychiatry, Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, UK.
authors.forename: D M
authors.initials: DM
authors.lastname: Lisiecka
authors.affiliation: Autism Research Centre, Department of Psychiatry, University of Cambridge, Cambridge, UK.
authors.forename: R
authors.initials: R
authors.lastname: Holt
authors.affiliation: Department of Psychiatry, Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, UK.
authors.forename: R
authors.initials: R
authors.lastname: Tait
authors.affiliation: Department of Physics, University of Cambridge, Cambridge, UK.
authors.forename: M
authors.initials: M
authors.lastname: Ford
authors.affiliation: 1] Autism Research Centre, Department of Psychiatry, University of Cambridge, Cambridge, UK [2] Department of Psychiatry, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan.
authors.forename: M-C
authors.initials: MC
authors.lastname: Lai
authors.affiliation: Autism Research Centre, Department of Psychiatry, University of Cambridge, Cambridge, UK.
authors.forename: L R
authors.initials: LR
authors.lastname: Chura
authors.affiliation: 1] Department of Psychiatry, Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, UK [2] Autism Research Centre, Department of Psychiatry, University of Cambridge, Cambridge, UK [3] Cambridge and Peterborough NHS Foundation Trust, Cambridge, UK.
authors.forename: S
authors.initials: S
authors.lastname: Baron-Cohen
authors.affiliation: 1] Autism Research Centre, Department of Psychiatry, University of Cambridge, Cambridge, UK [2] West Suffolk Hospital NHS Trust, Bury St Edmunds, UK.
authors.forename: M D
authors.initials: MD
authors.lastname: Spencer
authors.affiliation: 1] Brain Mapping Unit, Department of Psychiatry, University of Cambridge, Cambridge, UK [2] Department of Psychiatry, Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, UK [3] Cambridge and Peterborough NHS Foundation Trust, Cambridge, UK.
authors.forename: J
authors.initials: J
authors.lastname: Suckling
mesh_terms: D000293:Adolescent; D041923:Adolescent Development / Q000502:physiology*; D000328:Adult; D000367:Age Factors; D001321:Autistic Disorder / Q000473:pathology*; D002648:Child; D056324:Diffusion Tensor Imaging; D058068:Endophenotypes; D005260:Female; D006801:Humans; D008297:Male; D010641:Phenotype; D035781:Siblings; D066127:White Matter / Q000473:pathology*; D055815:Young Adult