Friday, February 17, 2017

Measuring brain growth in infancy may predict autism

Hazlett HC, Gu H, Munsell BC, Kim SH, Styner M, Wolff JJ, Elison JT, Swanson MR, Zhu H, Botteron KN, Collins DL, Constantino JN, Dager SR, Estes AM, Evans AC, Fonov VS, Gerig G, Kostopoulos P, McKinstry RC, Pandey J, Paterson S, Pruett JR, Schultz RT, Shaw DW, Zwaigenbaum L, Piven J; IBIS Network.; Clinical Sites.; Data Coordinating Center.; Image Processing Core.; Statistical Analysis.. Early brain development in infants at high risk for autism spectrum disorder. Nature. 2017 Feb 15;542(7641):348-351.

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.

From the article:

Studies have long shown that individuals with autism have enlarged brains compared with nonaffected individuals. But it hasn't been clear when this change in brain size occurs or how it effects the emergence of the behavioral characteristics associated with autism, explain Heather Cody Hazlett, PhD, an assistant professor at the University of North Carolina (UNC) School of Medicine in Chapel Hill, and colleagues…

In 15 high-risk infants who were diagnosed with autism at 24 months, the imaging revealed "hyperexpansion" of cortical surface area between 6 and 12 months. Then, between 12 and 24 months, they developed brain overgrowth. This overgrowth coincided with the emergence of symptoms and was linked to how severe the symptoms were.

Given the strength of this association, the researchers developed a computer algorithm to predict which high-risk children would later be diagnosed with autism. They used previously collected data on brain growth among infants between 6 and 12 months of age, including 34 who went on to develop the disorder and 145 who did not.

In cross-validation testing, the algorithm correctly predicted which children would be diagnosed with autism 81% of the time (accurately identifying 30 of 37 who were diagnosed) and had a sensitivity of 88%. It correctly predicted which children would not develop the disorder 97% of the time (138 of 142). 

"Our study shows that early brain development biomarkers could be very useful in identifying babies at the highest risk for autism before behavioral symptoms emerge," said senior author Joseph Piven, MD, director of the Carolina Institute for Developmental Disabilities at UNC, in a press release.

Already, studies have suggested that starting interventions early — shortly after behavioral symptoms emerge — tends to provide the greatest benefits. So, having a test available that could identify the disorder earlier might facilitate even earlier therapy.

"If we are able to replicate these results in further studies, these findings promise to change how we approach infant and toddler screening for autism, making it possible to identify infants who will later develop autism before the behavioral symptoms of autism become apparent," said coauthor Robert T. Schultz, PhD, director of the Center for Autism Research at the Children's Hospital of Philadelphia, Pennsylvania, in the release.

Additionally, Dr Schultz noted the imaging results show precisely where unusual brain development patterns begin in infants who later develop autism. Studying the mechanisms that underlie these very early brain changes may help scientists develop treatments that could be administered before further changes occur. 

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