title: Whole-brain functional hypoconnectivity as an endophenotype of autism in adolescents.
abstract: Endophenotypes are heritable and quantifiable markers that may assist in the identification of the complex genetic underpinnings of psychiatric conditions. Here we examined global hypoconnectivity as an endophenotype of autism spectrum conditions (ASCs). We studied well-matched groups of adolescent males with autism, genetically-related siblings of individuals with autism, and typically-developing control participants. We parcellated the brain into 258 regions and used complex-network analysis to detect a robust hypoconnectivity endophenotype in our participant group. We observed that whole-brain functional connectivity was highest in controls, intermediate in siblings, and lowest in ASC, in task and rest conditions. We identified additional, local endophenotype effects in specific networks including the visual processing and default mode networks. Our analyses are the first to show that whole-brain functional hypoconnectivity is an endophenotype of autism in adolescence, and may thus underlie the heritable similarities seen in adolescents with ASC and their relatives.
authors.affiliation: Department of Psychiatry, Brain Mapping Unit, University of Cambridge, Cambridge, UK.
authors.forename: R L
authors.initials: RL
authors.lastname: Moseley
authors.affiliation: Department of Psychiatry, Brain Mapping Unit, University of Cambridge, Cambridge, UK ; University of Cambridge, Hughes Hall, Cambridge, UK.
authors.forename: R J F
authors.initials: RJ
authors.lastname: Ypma
authors.affiliation: Autism Research Centre, Department of Psychiatry, University of Cambridge, Cambridge, UK.
authors.forename: R J
authors.initials: RJ
authors.lastname: Holt
authors.affiliation: Autism Research Centre, Department of Psychiatry, University of Cambridge, Cambridge, UK.
authors.forename: D
authors.initials: D
authors.lastname: Floris
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: Autism Research Centre, Department of Psychiatry, University of Cambridge, Cambridge, UK.
authors.forename: M D
authors.initials: MD
authors.lastname: Spencer
authors.affiliation: Autism Research Centre, Department of Psychiatry, University of Cambridge, Cambridge, UK ; Cambridge Lifespan Asperger Syndrome Service (CLASS) Clinic, Cambridgeshire and Peterborough National Health Service Foundation Trust, Cambridge, UK.
authors.forename: S
authors.initials: S
authors.lastname: Baron-Cohen
authors.affiliation: Department of Psychiatry, Brain Mapping Unit, University of Cambridge, Cambridge, UK ; Department of Experimental Psychology, Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, UK ; Cambridgeshire & Peterborough National Health Service Foundation Trust, Cambridge, UK.
authors.forename: J
authors.initials: J
authors.lastname: Suckling
authors.affiliation: Department of Psychiatry, Brain Mapping Unit, University of Cambridge, Cambridge, UK ; Department of Experimental Psychology, Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, UK ; Cambridgeshire & Peterborough National Health Service Foundation Trust, Cambridge, UK ; ImmunoPsychiatry, Alternative Discovery & Development, GlaxoSmithKline, Stevenage, UK.
authors.forename: E
authors.initials: E
authors.lastname: Bullmore
authors.affiliation: Department of Psychiatry, Brain Mapping Unit, University of Cambridge, Cambridge, UK ; Churchill College, University of Cambridge, Cambridge, UK.
authors.forename: M
authors.initials: M
authors.lastname: Rubinov
mesh_terms: D000293:Adolescent; D000067877:Autism Spectrum Disorder / Q000473:pathology* / Q000503:physiopathology*; D001921:Brain / Q000473:pathology* / Q000503:physiopathology*; D001931:Brain Mapping; D058068:Endophenotypes; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D035781:Siblings