Homogeneous Subgroups of Autism Spectrum Disorder Based on Behavioral, Developmental, and Medical Phenotypes
Autism spectrum disorder (ASD) is a complex developmental disorder characterized by deficits in social communication and interaction skills, and the presence of restricted interests and repetitive behaviors that manifest in early childhood. Children with ASD present with remarkable heterogeneity in symptom presentation that ranges from severe impairments that require substantial supports to less noticeable impairments that require fewer supports. Defining the phenotypic complexity among those with ASD may help elucidate distinct etiologies that contribute to symptom development.
The current study explores ASD subgroups based on behavioral, developmental, and medical phenotypes along the ASD continuum.
The Study to Explore Early Development (SEED) is a case-control study designed to examine ASD phenotypes and etiologies. Children 2-5 years old were ascertained through birth certificate records and multiple sources that serve children with developmental problems. All children were screened for ASD upon enrollment. After an in-person developmental evaluation, children were classified into one of the following groups based on degree of ASD symptomology noted on the ASD screen and developmental assessments: ASD, developmental delay or disorder (DD) with ASD symptoms, DD without ASD symptoms, and population comparison.
Phenotypic characteristics and behaviors hypothesized to be associated with ASD were obtained via the Autism Diagnostic Observation Schedule, Mullen Scale of Early Learning (MSEL) and child’s birth certificate record, and parent report on the Autism Diagnostic Interview – Revised, Child Behavior Checklist, Child Sleep Characteristics Questionnaire, Early Development Questionnaire, Gastrointestinal Questionnaire (created for SEED), Social Responsiveness Scale, and a structured interview that obtained information on demographics and health conditions previously diagnosed by a healthcare provider.
Subgrouping variables were identified via a multi-stage process. Members of the author group first reviewed subgrouping variables used in previous studies and discussed aspects of the ASD phenotype that best characterized children with ASD. Twenty seven variables were selected based on the literature review, clinical and epidemiological expertise, and availability of data in SEED. Subgroups of children with ASD were identified via latent class analysis.
There were 707 children classified as ASD and 305 children classified as DD with ASD symptoms included in the analyses. The sample was 79.9% male, and 54.8% White, 22.2% Black, 12.3% Multiracial, 5.1% Asian, and 5.6% other or unreported race. Children with ASD had a mean MSEL score of 66.9 whereas children defined as DD with ASD symptoms had a mean MSEL score of 79.0 (p<.01).
Data analyses, discussion, and interpretation are underway. Preliminary results reveal a 4-class model distinguished by phenotypic characteristics beyond MSEL scores (e.g., age at first social smile, aggressive and anxious behaviors, developmental regression, diet restrictions, emotional reactivity, repetitive behaviors, restricted interests, self-injurious behaviors, and somatic complaints). Detailed results will be available at the time of presentation.
Due to its comprehensive data collection and inclusion of children with a range of ASD symptoms, SEED represents a distinct opportunity to explore ASD subgroups based on behavioral, developmental, and medical phenotypes. Consequently, the results of this study will likely inform future studies on the etiology, trajectory, and treatment of ASD.