Wendy Stone - US grants

The primary objective of this study is to identify the diagnostic features of autism that are present in children under 36 months of age. Although many authors have alluded to developmental changes in symptom expression, empirical study of the early manifestations of autism has been scant. The study of early symptoms has important clinical and theoretical implications. At a clinical level, children identified at young ages can accrue the benefits of early participation in specialized intervention programs. Moreover, identification of early patterns of symptom expression can contribute to our understanding of the primary deficits of autism. This study will employ a prospective, longitudinal research design. Fifty children under 36 months of age who demonstrate behavioral characteristics within the "autism spectrum" will be followed through the age of 4 years, at which time they will receive a definitive clinical diagnosis. Clinical and diagnostic assessments will occur at the ages of 2, 3, and 4 years, and will include measures of developmental/cognitive functioning, receptive and expressive language skills, adaptive behavior, and severity of autism. Diagnostic assessment will be performed independently by two experienced clinicians. Home and classroom observations will be conducted at the ages of 2 and 3 years to evaluate the influence of environmental factors on the early developmental course of this disorder. The design and methodology of this study will enable us to determine: 1) the reliability of the diagnosis of autism made below the age of 36 months; 2) the early symptoms that are predictive of a definitive diagnosis of autism at 4 years; and 3) the factors that are associated with changes in symptomatology over the two-year period. This project represents an improvement over previous studies in its inclusion of a larger sample, use of prospective rather tan retrospective methodology, evaluation of interobserver agreement for clinical diagnosis, and consideration of environmental influences on changes in symptomatology.

DESCRIPTION (provided by applicant): Most of the treatment literature for young children with autism consists of either full-scale, comprehensive intervention programs evaluated on broad outcomes, or highly specialized interventions evaluated on narrowly focused outcomes. Neither approach has succeeded in describing for whom, and under what conditions, a given intervention should be used. The present project will describe a sequential approach for identifying and testing potential predictors of responsiveness to interventions for specific skill deficits. Motor imitation is the core skill addressed in this project, because it not only plays a pivotal role in the social and cognitive development of children with typical development, but also has been described as a core deficit for young children with autism. Three studies will be conducted with 2- and 3-year-old children with autism. Study 1 will identify which organismic factors (i.e., developmental precursors of the target skill) and environmental factors (e.g., family risks and opportunities) are predictors of motor imitation development, using a longitudinal correlational design. Study 2 will evaluate the effectiveness of a novel imitation intervention that combines both contingent imitation and embedded trials, on children who are high on the predictors identified in Study 1. Study 3 will determine whether the intervention is differentially effective in increasing generalized imitation in children who score high and low on the predictor skills. The results of this research will have implications for the design of interventions for other core deficits of autism.

DESCRIPTION (provided by applicant): Although siblings of children with autism have been found to be at elevated risk for social and communication impairments, research has not yet focused on the very early development of these children. The primary advantage of studying young siblings of children with autism is the opportunity it affords for the identification and remediation of early deficits that could have adverse effects on subsequent development. Deficits in social-communicative behaviors are the most prominent early symptoms in children with autism, and have recently been hypothesized to indicate the presence of a fundamental, autism-specific "social orienting" impairment. The proposed project will study the early development of four dimensions of social orienting (i.e., initiating affect, initiating attention, responding to affect, responding to attention). In typically developing infants, these classes of behavior appear quite early and set the stage for the emergence of important developmental accomplishments such as establishing social-emotional reciprocity and using referential language. Social orienting behaviors will be examined longitudinally in two sibling groups: younger siblings of children with autism spectrum disorders (SIB-ASD) and younger siblings of typically-developing children (SIB-TD) who are CA-matched. Children in both groups will enter the study between 12 and 18 months of age and will be followed for two years (i.e., through ages 36-42 months). Social orienting behaviors will be measured at six time points over the 2-year period, and social and language outcomes will be measured at the end point. Additionally, two age-matched comparison samples will be recruited to provide end-point references for social orienting behavior: children with ASD and children with nonautistic developmental delays (DD). The inclusion of these samples will enable us to compare social orienting at age 3 in siblings of children with ASD with that of: a) children with typical development; b) children with ASD; and c) children with DD. This project represents a unique contribution to the autism literature in its focus on very young siblings of children with autism; its systematic examination of different components of social orienting; its longitudinal design; and its use of ASD and DD cross-sectional samples at age 3 to provide benchmarks for delay and deviance in social orienting skills.

DESCRIPTION (provided by applicant): Although siblings of children with autism have been found to be at elevated risk for social and communication impairments, research has not yet focused on the very early development of these children. The primary advantage of studying young siblings of children with autism is the opportunity it affords for the identification and remediation of early deficits that could have adverse effects on subsequent development. Deficits in social-communicative behaviors are the most prominent early symptoms in children with autism, and have recently been hypothesized to indicate the presence of a fundamental, autism-specific "social orienting" impairment. The proposed project will study the early development of four dimensions of social orienting (i.e., initiating affect, initiating attention, responding to affect, responding to attention). In typically developing infants, these classes of behavior appear quite early and set the stage for the emergence of important developmental accomplishments such as establishing social-emotional reciprocity and using referential language. Social orienting behaviors will be examined longitudinally in two sibling groups: younger siblings of children with autism spectrum disorders (SIB-ASD) and younger siblings of typically-developing children (SIB-TD) who are CA-matched. Children in both groups will enter the study between 12 and 18 months of age and will be followed for two years (i.e., through ages 36-42 months). Social orienting behaviors will be measured at six time points over the 2-year period, and social and language outcomes will be measured at the end point. Additionally, two age-matched comparison samples will be recruited to provide end-point references for social orienting behavior: children with ASD and children with nonautistic developmental delays (DD). The inclusion of these samples will enable us to compare social orienting at age 3 in siblings of children with ASD with that of: a) children with typical development; b) children with ASD; and c) children with DD. This project represents a unique contribution to the autism literature in its focus on very young siblings of children with autism; its systematic examination of different components of social orienting; its longitudinal design; and its use of ASD and DD cross-sectional samples at age 3 to provide benchmarks for delay and deviance in social orienting skills.

[unreadable] DESCRIPTION (provided by applicant): Infant siblings of children with ASD exhibit substantial variability in their social-communicative outcomes: some manifest behaviors consistent with an autism spectrum diagnosis, others exhibit less severe symptoms such as language delay, and others evidence no detectable disorder. This cross-site, Vanderbilt- Miami project will examine the extent to which early impairments in specific attentional and affective mechanisms - both of which are putative core deficits of autism - explain the behavioral heterogeneity that is observed in these high-risk children. We focus specifically on the domains of attention coordination and positive affective competencies, and examine their development across the first two years of postnatal life (i.e., from 6 to 18 months) and their relation to later social and communicative outcomes at age 24 and 36 months. The overarching hypotheses are that there will be developmental continuity in these domains across the first two years, that early differences in these domains will be evident between groups at high- and low-risk for ASD, and that early impairments will predict individual differences in social and communicative outcomes observed in later-born ASD siblings. Specific areas of investigation include the relation between positive affective competencies in dyadic and triadic contexts across the first year of life, the contributions of early positive affective competencies and attention coordination to the emergence of positive joint attention competencies in the second year of life, and the extent to which individual differences in early positive affective competencies and attention coordination contribute to later autism symptomatology. This prospective longitudinal project will compare developmental trajectories and outcomes in 200 infant siblings of children diagnosed with ASD (Sib-ASD) and 100 infant siblings of typically developing children (Sib-TD). A split panel longitudinal design will allow us to examine development both within- and across- age-group cohorts from 6 months to 36 months of age. This project employs novel methods and measurement of infant behavior including electrophysiological and eye tracking measures, measures of positive affect communication and representation, and longitudinal measures of sharing positive emotion about objects with others. Longitudinal structural equation modeling and mixed modeling procedures are utilized to assess differences in the development of typically developing and at- risk siblings and to predict heterogeneity in the outcomes of the at-risk siblings of children with ASD. The project employs a developmental psychopathology perspective to shed light on normative and disturbed longitudinal pathways toward heterogenous outcomes. PUBLIC HEALTH RELEVANCE: The prospective study of younger siblings of children with ASD offers an ideal opportunity to learn about the earliest signs of autism as well as the development, manifestation, and boundaries of the broader autism phenotype. This information is critical for understanding the causes of autism and for developing more effective and targeted treatments. [unreadable] [unreadable] [unreadable]

DESCRIPTION (provided by applicant): Although caregivers often become concerned about their child by 17-19 months of age, children do not typically receive a diagnosis of autism spectrum disorder (ASD) until they are 41/2 years old, or older for Hispanic families. It is now well documented that early participation in ASD-specialized intervention can lead to significant improvements in skills and behavior for toddlers with ASD. However, despite the availability of publicly funded Part C early intervention (EI) services, long waits for a formal ASD diagnosis can prevent toddlers from receiving appropriately specialized intervention during the critical birth-to-three years. In addition, caregivers concerned about ASD experience high levels of uncertainty and stress during this waiting period. This project will implement and evaluate an innovative healthcare service delivery model designed to promote earlier access to specialized intervention for toddlers with ASD. The Screen-Refer-Treat (SRT) model provides a coordinated and cost-effective approach to early identification and intervention by involving both medical and EI providers, and represents a practical and sustainable strategy for bridging the gap between ASD concerns and ASD intervention. The SRT model, which builds on the availability of validated ASD screening tools and low-cost behaviorally-based ASD interventions, will be implemented in four diverse communities across Washington State to evaluate changes in service delivery practices for toddlers with Hispanic as well as Non- Hispanic backgrounds. The SRT model comprises three components: (1) universal ASD screening at 16-20 months and prompt referral to EI programs by primary care physicians (PCPs); (2) expedited ASD assessments within EI programs; and (3) use of an inexpensive, evidence-based ASD-specialized intervention by EI providers. An electronic version of the Modified Checklist for Autism (M-CHAT) with automated scoring that incorporates relevant follow-up questions will be provided to PCP practices, and distance coaching via telemedicine will be available to EI providers to support their ASD assessment and intervention activities. A stepped wedge cluster RCT design will be used to evaluate implementation and outcomes of the SRT model. Data on screening, referral, assessment, and intervention practices will be collected from 40 PCPs and 80 EI providers across the state prior to and following SRT implementation to identify practice changes. In addition, separate samples of caregivers of toddlers with ASD concerns (n=245) will be recruited from communities before and after SRT implementation and followed prospectively to measure differences and changes over time in caregiver well- being, parenting efficacy, satisfaction with healthcare systems, and toddler's social-communicative behaviors. We predict that implementation of the SRT model will be associated with higher rates of ASD screening by PCPs, earlier referral to EI programs, earlier initiation of ASD-specialized intervention, reduced time between ASD concerns and diagnosis, and improved caregiver and child outcomes.

PROJECT SUMMARY Despite strong consensus that early, specialized intervention for children with Autism Spectrum Disorder (ASD) can have a dramatic impact on outcomes, the U.S. health system?s capacity to provide such services is severely challenged by the rapid rise in ASD prevalence. The long-term goal is to improve outcomes for children with early signs of ASD by increasing the capacity to provide appropriately specialized treatment within an existing infrastructure: the Part C Early Intervention (EI) service delivery system. Part C is publicly funded, available in all areas, and serves children under age 3 who have developmental delays or disabilities. Currently, the effectiveness of EI services is limited by high practice variation and infrequent use of evidence- based interventions. The study objective is to improve services and outcomes for children with early signs of ASD by conducting a randomized controlled trial (RCT) testing the effectiveness of training EI providers to deliver Reciprocal Imitation Training (RIT). RIT is a naturalistic developmental behavioral intervention (NDBI) that is ideally suited for EI settings because it is low intensity, play-based, easy to learn and implement, and can be taught to families for their independent use, thus increasing intervention dosage. This RCT will employ a hybrid type 1 effectiveness/implementation design, and will use a unique mixed methods approach to gather evidence that will be essential for implementing RIT at scale, pending positive trial results. The sample includes 20 EI agencies across 4 U.S. States and comprises a total of 160 EI providers and 440 families of children with early symptoms of ASD, which not only provides a robust sample size, but also affords the opportunity to assess generalizability of this approach across regions that vary in their implementation of Part C services. EI providers will be randomly assigned to the RIT training group (n=80) or treatment as usual (TAU; n=80). Providers in both groups will identify 2-5 children in their caseload who are 16-30 months old with early symptoms of ASD (n=220 children per group). Intensive, state-of-the art, multi- method assessment technology will be used to measure the impact of the intervention on children?s language and social communication, as well as parents? self-efficacy and well-being. Importantly, this study will examine putative mechanisms (i.e., child gains in imitation and joint attention; parent contingent responsiveness) through which the intervention improves clinically-relevant outcomes. Data regarding provider-initiated modifications to the intervention and delivery will be analyzed to identify fidelity-consistent vs. fidelity- inconsistent changes, which will inform refinement of future RIT training and quality assurance procedures. In sum, this study will generate the evidence necessary to implement RIT at scale, thereby increasing the capacity of the existing EI system to deliver effective, evidence-based intervention to the rapidly growing population of children who show early signs of ASD.