Katarzyna Chawarska1, Frederick Shic2, Suzanne Macari2, Daniel J Campbell3, Jessica Brian4, Rebecca Landa5, Ted Hutman6, Charles A Nelson7, Sally Ozonoff8, Helen Tager-Flusberg9, Gregory S Young8, Lonnie Zwaigenbaum10, Ira L Cohen11, Tony Charman12, Daniel S Messinger13, Ami Klin14, Scott Johnson6, Susan Bryson15. 1. Yale University School of Medicine, New Haven, CT. Electronic address: Katarzyna.chawarska@yale.edu. 2. Yale University School of Medicine, New Haven, CT. 3. Amgen Inc., Thousand Oaks, CA. 4. University of Toronto. 5. Kennedy Krieger Institute and Johns Hopkins School of Medicine, Baltimore. 6. University of California, Los Angeles. 7. Harvard Medical School and Boston Children's Hospital. 8. Medical Investigation of Neurodevelopmental Disorders (MIND) Institute at the University of California, Davis. 9. Boston University. 10. University of Alberta, Edmonton, Alberta, Canada. 11. New York State Institute for Basic Research in Developmental Disabilities, Albany, NY. 12. Institute of Psychiatry, King's College London. 13. University of Miami. 14. Marcus Autism Center, Children's Healthcare of Atlanta, and Emory University, Atlanta. 15. Dalhousie University, Halifax, Canada.
Abstract
OBJECTIVE: Younger siblings of children with autism spectrum disorder (ASD) are at high risk (HR) for developing ASD as well as features of the broader autism phenotype. Although this complicates early diagnostic considerations in this cohort, it also provides an opportunity to examine patterns of behavior associated specifically with ASD compared to other developmental outcomes. METHOD: We applied Classification and Regression Trees (CART) analysis to individual items of the Autism Diagnostic Observation Schedule (ADOS) in 719 HR siblings to identify behavioral features at 18 months that were predictive of diagnostic outcomes (ASD, atypical development, and typical development) at 36 months. RESULTS: Three distinct combinations of features at 18 months were predictive of ASD outcome: poor eye contact combined with lack of communicative gestures and giving; poor eye contact combined with a lack of imaginative play; and lack of giving and presence of repetitive behaviors, but with intact eye contact. These 18-month behavioral profiles predicted ASD versus non-ASD status at 36 months with 82.7% accuracy in an initial test sample and 77.3% accuracy in a validation sample. Clinical features at age 3 years among children with ASD varied as a function of their 18-month symptom profiles. Children with ASD who were misclassified at 18 months were higher functioning, and their autism symptoms increased between 18 and 36 months. CONCLUSION: These findings suggest the presence of different developmental pathways to ASD in HR siblings. Understanding such pathways will provide clearer targets for neural and genetic research and identification of developmentally specific treatments for ASD.
OBJECTIVE: Younger siblings of children with autism spectrum disorder (ASD) are at high risk (HR) for developing ASD as well as features of the broader autism phenotype. Although this complicates early diagnostic considerations in this cohort, it also provides an opportunity to examine patterns of behavior associated specifically with ASD compared to other developmental outcomes. METHOD: We applied Classification and Regression Trees (CART) analysis to individual items of the Autism Diagnostic Observation Schedule (ADOS) in 719 HR siblings to identify behavioral features at 18 months that were predictive of diagnostic outcomes (ASD, atypical development, and typical development) at 36 months. RESULTS: Three distinct combinations of features at 18 months were predictive of ASD outcome: poor eye contact combined with lack of communicative gestures and giving; poor eye contact combined with a lack of imaginative play; and lack of giving and presence of repetitive behaviors, but with intact eye contact. These 18-month behavioral profiles predicted ASD versus non-ASD status at 36 months with 82.7% accuracy in an initial test sample and 77.3% accuracy in a validation sample. Clinical features at age 3 years among children with ASD varied as a function of their 18-month symptom profiles. Children with ASD who were misclassified at 18 months were higher functioning, and their autism symptoms increased between 18 and 36 months. CONCLUSION: These findings suggest the presence of different developmental pathways to ASD in HR siblings. Understanding such pathways will provide clearer targets for neural and genetic research and identification of developmentally specific treatments for ASD.
Authors: Suzanne L Macari; Grace C Wu; Kelly K Powell; Scuddy Fontenelle; Deanna M Macris; Katarzyna Chawarska Journal: J Autism Dev Disord Date: 2018-04
Authors: Amy S Weitlauf; Alison C Vehorn; Wendy L Stone; Deborah Fein; Zachary E Warren Journal: J Dev Behav Pediatr Date: 2015-09 Impact factor: 2.225
Authors: Robert W Emerson; Chloe Adams; Tomoyuki Nishino; Heather Cody Hazlett; Jason J Wolff; Lonnie Zwaigenbaum; John N Constantino; Mark D Shen; Meghan R Swanson; Jed T Elison; Sridhar Kandala; Annette M Estes; Kelly N Botteron; Louis Collins; Stephen R Dager; Alan C Evans; Guido Gerig; Hongbin Gu; Robert C McKinstry; Sarah Paterson; Robert T Schultz; Martin Styner; Bradley L Schlaggar; John R Pruett; Joseph Piven Journal: Sci Transl Med Date: 2017-06-07 Impact factor: 17.956