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Early Brain Development in Infants at High Risk for Autism Spectrum Disorder

Department of Psychiatry, University of North Carolina, Chapel Hill, NC, USA.
Nature Publishing Group
Publication Date:
Volume Number:
Issue Number:
Nature. 2017 Feb 15;542(7641):348-51.
PubMed ID:
autism, brain, neuroimaging, development
Appears in Collections:
R01 MH093510/MH/NIMH NIH HHS/United States
U54 EB005149/EB/NIBIB NIH HHS/United States
U54 HD087011/HD/NICHD NIH HHS/United States
R01 MH086633/MH/NIMH NIH HHS/United States
P30 HD003110/HD/NICHD NIH HHS/United States
AS6020/Autism Speaks/United States
R01 HD055741/HD/NICHD NIH HHS/United States
Generated Citation:
Hazlett H.C., Gu H., Munsell B.C., Kim S.H., Styner M., Wolff J.J., Elison J.T., Swanson M.R., Zhu H., Botteron K.N., Collins D.L., Constantino J.N., Dager S.R., Estes A.M., Evans A.C., Fonov V.S., Gerig G., Kostopoulos P., McKinstry R.C., Pandey J., Paterson S., Pruett J.R., Schultz R.T., Shaw D.W., Zwaigenbaum L., Piven J. Early Brain Development in Infants at High Risk for Autism Spectrum Disorder. Nature. 2017 Feb 15;542(7641):348-51. PMID: 28202961. PMCID: PMC5336143.
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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.

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