Chawarska Katarzyna, Shic Frederick, Macari Suzanne, Campbell Daniel J, Brian Jessica, Landa Rebecca, Hutman Ted, Nelson Charles A, Ozonoff Sally, Tager-Flusberg Helen, Young Gregory S, Zwaigenbaum Lonnie, Cohen Ira L, Charman Tony, Messinger Daniel S, Klin Ami, Johnson Scott, Bryson Susan
Yale University School of Medicine, New Haven, CT.
Yale University School of Medicine, New Haven, CT.
J Am Acad Child Adolesc Psychiatry. 2014 Dec;53(12):1317-1327.e1. doi: 10.1016/j.jaac.2014.09.015. Epub 2014 Oct 2.
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.
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.
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.
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.
自闭症谱系障碍(ASD)患儿的弟弟妹妹患ASD以及具有更广泛自闭症表型特征的风险很高。尽管这使该队列的早期诊断考虑变得复杂,但它也提供了一个机会,来检查与其他发育结果相比,与ASD特异性相关的行为模式。
我们对719名高风险兄弟姐妹的自闭症诊断观察量表(ADOS)的各个项目应用分类与回归树(CART)分析,以确定18个月时可预测36个月诊断结果(ASD、非典型发育和典型发育)的行为特征。
18个月时三种不同的特征组合可预测ASD结果:眼神接触不良并伴有缺乏交流手势和给予行为;眼神接触不良并伴有缺乏想象性游戏;缺乏给予行为且存在重复行为,但眼神接触正常。这些18个月时的行为特征在初始测试样本中预测36个月时ASD与非ASD状态的准确率为82.7%,在验证样本中的准确率为77.3%。ASD患儿3岁时的临床特征因18个月时的症状特征而异。18个月时被误分类的ASD患儿功能较高,且其自闭症症状在18至36个月之间有所增加。
这些发现表明高风险兄弟姐妹中存在通往ASD的不同发育途径。了解这些途径将为神经和基因研究以及确定针对ASD的发育特异性治疗提供更明确的目标。