Profiling clinical heterogeneity in Autism Spectrum Disorder at time of children's diagnosis: A cluster analysis from the ELENA cohort

Abstract

Background: Autism Spectrum Disorder (ASD) encompass a heterogeneous group of neurodevelopmental conditions characterized by deficits in social communication and repetitive behaviors. The rising prevalence of ASD highlights the urgent need for effective diagnostic and intervention strategies. However, the significant clinical, cognitive and etiological heterogeneity within ASD populations poses substantial challenges to these efforts.

Aims: This study aimed to identify distinct ASD subtypes at time of diagnosis within the ELENA cohort by incorporating not only DSM-5 criteria but also measures of adaptive functioning and behavioral problems.

Material and methods: Data from 458 children and adolescents with ASD were analyzed using hierarchical agglomerative clustering. Variables included autistic symptoms, intellectual quotient, adaptive behavior and behavioral problems. Clusters were identified based on these parameters, and post-hoc analyses were conducted to assess statistically significant differences in sex and age among the four clusters using Chi-square test and Student's t-tests.

Results: Four distinct clusters were identified from the analysis: (1) High Autistic Symptom Severity with Lowest Behavioral Problems, (2) High Autistic Symptom Severity with High Behavioral Problems, (3) Low Autistic Symptom Severity with Highest Behavioral Problems and (4) Low Autistic Symptom Severity with low behavioral problems, while significant age differences were observed across clusters, no significant sex differences were found.

Discussion: These clusters exhibited significant variability in adaptive functioning and behavioral problems, suggesting that DSM-5 criteria alone do not fully capture the complexity of ASD. The findings underscore the importance of incorporating measures of adaptive functioning and behavioral problems into ASD assessments and interventions. Future research should aim to validate these clusters in larger and more diverse populations and explore the integration of genetic and neuroimaging data to further refine the characterization of ASD subtypes. Additionally, longitudinal studies are needed to assess the stability and clinical relevance of these subtypes over time.

Trial registration number: NCT02625116.

Keywords: Adaptive functioning; Autism Spectrum Disorder; Behavioral problems; Clinical heterogeneity; Cluster analysis.