title: Early brain development in infants at high risk for autism spectrum disorder.
abstract: Brain enlargement has been observed in children with autism spectrum disorder (ASD), but the timing of this phenomenon, and the relationship between ASD and the appearance of behavioural symptoms, are unknown. Retrospective head circumference and longitudinal brain volume studies of two-year olds followed up at four years of age have provided evidence that increased brain volume may emerge early in development. Studies of infants at high familial risk of autism can provide insight into the early development of autism and have shown that characteristic social deficits in ASD emerge during the latter part of the first and in the second year of life. These observations suggest that prospective brain-imaging studies of infants at high familial risk of ASD might identify early postnatal changes in brain volume that occur before an ASD diagnosis. In this prospective neuroimaging study of 106 infants at high familial risk of ASD and 42 low-risk infants, we show that hyperexpansion of the cortical surface area between 6 and 12 months of age precedes brain volume overgrowth observed between 12 and 24 months in 15 high-risk infants who were diagnosed with autism at 24 months. Brain volume overgrowth was linked to the emergence and severity of autistic social deficits. A deep-learning algorithm that primarily uses surface area information from magnetic resonance imaging of the brain of 6-12-month-old individuals predicted the diagnosis of autism in individual high-risk children at 24 months (with a positive predictive value of 81% and a sensitivity of 88%). These findings demonstrate that early brain changes occur during the period in which autistic behaviours are first emerging.
authors.affiliation: Department of Psychiatry, University of North Carolina, Chapel Hill, North Carolina 27599, USA.|Carolina Institute for Developmental Disabilities, Chapel Hill, North Carolina 27599, USA.
authors.forename: Heather Cody
authors.initials: HC
authors.lastname: Hazlett
authors.affiliation: Department of Psychiatry, University of North Carolina, Chapel Hill, North Carolina 27599, USA.
authors.forename: Hongbin
authors.initials: H
authors.lastname: Gu
authors.affiliation: College of Charleston, Charleston, South Carolina 29424, USA.
authors.forename: Brent C
authors.initials: BC
authors.lastname: Munsell
authors.affiliation: Department of Psychiatry, University of North Carolina, Chapel Hill, North Carolina 27599, USA.
authors.forename: Sun Hyung
authors.initials: SH
authors.lastname: Kim
authors.affiliation: Department of Psychiatry, University of North Carolina, Chapel Hill, North Carolina 27599, USA.
authors.forename: Martin
authors.initials: M
authors.lastname: Styner
authors.affiliation: Department of Educational Psychology, University of Minnesota, Minneapolis, Minnesota 55455, USA.
authors.forename: Jason J
authors.initials: JJ
authors.lastname: Wolff
authors.affiliation: Institute of Child Development, University of Minnesota, Minneapolis, Minnesota 55455, USA.
authors.forename: Jed T
authors.initials: JT
authors.lastname: Elison
authors.affiliation: Carolina Institute for Developmental Disabilities, Chapel Hill, North Carolina 27599, USA.
authors.forename: Meghan R
authors.initials: MR
authors.lastname: Swanson
authors.affiliation: Department of Biostatistics, University of North Carolina, Chapel Hill, North Carolina 27599, USA.
authors.forename: Hongtu
authors.initials: H
authors.lastname: Zhu
authors.affiliation: Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
authors.forename: Kelly N
authors.initials: KN
authors.lastname: Botteron
authors.affiliation: Montreal Neurological Institute, McGill University, Montreal, Quebec H3A 0G4, Canada.
authors.forename: D Louis
authors.initials: DL
authors.lastname: Collins
authors.affiliation: Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
authors.forename: John N
authors.initials: JN
authors.lastname: Constantino
authors.affiliation: Department of Radiology, University of Washington, Seattle, Washington 98105, USA.|Center on Human Development and Disability, University of Washington, Seattle, Washington 98105, USA.
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Dager
authors.affiliation: Center on Human Development and Disability, University of Washington, Seattle, Washington 98105, USA.|Department of Speech and Hearing Sciences, University of Washington, Seattle, Washington 98105, USA.
authors.forename: Annette M
authors.initials: AM
authors.lastname: Estes
authors.affiliation: Montreal Neurological Institute, McGill University, Montreal, Quebec H3A 0G4, Canada.
authors.forename: Alan C
authors.initials: AC
authors.lastname: Evans
authors.affiliation: Montreal Neurological Institute, McGill University, Montreal, Quebec H3A 0G4, Canada.
authors.forename: Vladimir S
authors.initials: VS
authors.lastname: Fonov
authors.affiliation: Tandon School of Engineering, New York University, New York, New York 10003, USA.
authors.forename: Guido
authors.initials: G
authors.lastname: Gerig
authors.affiliation: Montreal Neurological Institute, McGill University, Montreal, Quebec H3A 0G4, Canada.
authors.forename: Penelope
authors.initials: P
authors.lastname: Kostopoulos
authors.affiliation: Mallinckrodt Institute of Radiology, Washington University, St. Louis, Missouri 63110, USA.
authors.forename: Robert C
authors.initials: RC
authors.lastname: McKinstry
authors.affiliation: Center for Autism Research, The Children's Hospital of Philadelphia and University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Juhi
authors.initials: J
authors.lastname: Pandey
authors.affiliation: Department of Psychology, Temple University, Philadelphia, Pennsylvania 19122, USA.
authors.forename: Sarah
authors.initials: S
authors.lastname: Paterson
authors.affiliation: Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
authors.forename: John R
authors.initials: JR
authors.lastname: Pruett
authors.affiliation: Center for Autism Research, The Children's Hospital of Philadelphia and University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Robert T
authors.initials: RT
authors.lastname: Schultz
authors.affiliation: Department of Radiology, University of Washington, Seattle, Washington 98105, USA.|Center on Human Development and Disability, University of Washington, Seattle, Washington 98105, USA.
authors.forename: Dennis W
authors.initials: DW
authors.lastname: Shaw
authors.affiliation: Department of Pediatrics, University of Alberta, Edmonton, Alberta T6G 2R3, Canada.
authors.forename: Lonnie
authors.initials: L
authors.lastname: Zwaigenbaum
authors.affiliation: Department of Psychiatry, University of North Carolina, Chapel Hill, North Carolina 27599, USA.|Carolina Institute for Developmental Disabilities, Chapel Hill, North Carolina 27599, USA.
authors.forename: Joseph
authors.initials: J
authors.lastname: Piven
mesh_terms: D000067877:Autism Spectrum Disorder / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology* / Q000523:psychology; D001921:Brain / Q000254:growth & development* / Q000473:pathology*; D002675:Child, Preschool; D005192:Family Health; D005260:Female; D006801:Humans; D007223:Infant; D008137:Longitudinal Studies; D008297:Male; D059906:Neuroimaging; D011379:Prognosis; D012306:Risk; D012919:Social Behavior