Features that best define the heterogeneity and homogeneity of autism in preschool‐age children: A multisite case–control analysis replicated across two independent samples

Abstract

The heterogeneous nature of children with symptoms of autism spectrum disorder (ASD) makes it difficult to identify risk factors and effective treatment options. We sought to identify behavioral and developmental features that best define the heterogeneity and homogeneity in 2-5-year-old children classified with ASD and subthreshold ASD characteristics. Children were enrolled in a multisite casecontrol study of ASD. Detailed behavioral and developmental data were gathered by maternal telephone interview, parent-administered questionnaires, child cognitive evaluation, and ASD diagnostic measures. Participants with a positive ASD screen score or prior ASD diagnosis were referred for comprehensive evaluation. Children in the ASD group met study criteria based on this evaluation; children who did not meet study criteria were categorized as having subthreshold ASD characteristics. There were 1480 children classified as ASD (81.6% boys) and 594 children classified as having subthreshold ASD characteristics (70.2% boys) in the sample. Factors associated with dysregulation (e.g., aggression, anxiety/ depression, sleep problems) followed by developmental abilities (e.g., expressive and receptive language skills) most contributed to heterogeneity in both groups of children. Atypical sensory response contributed to homogeneity in children classified as ASD but not those with subthreshold characteristics. These findings suggest that dysregulation and developmental abilities are clinical features that can impact functioning in children with ASD and other DD, and that documenting these features in pediatric records may help meet the needs of the individual child. Sensory dysfunction could be considered a core feature of ASD and thus used to inform more targeted screening, evaluation, treatment, and research efforts. Lay summaryThe diverse nature of autism spectrum disorder (ASD) makes it difficult to find risk factors and treatment options. We identified the most dissimilar and most similar symptom(s) in children classified as ASD and as having subthreshold ASD characteristics. Factors associated with dysregulation and developmental abilities contributed to diversity in both groups of children. Sensory dysfunction was the most common symptom in children with ASD but not those with subthreshold characteristics. Findings can inform clinical practice and research.

Heterogeneity thwarts autism explanatory power: A proposal for endophenotypes

“…Introduction: Heterogeneity thwarts autism explanatory power: Can transdiagnostic behavioral endophenotypes help? patterns, comorbidities, and biomarkers (3)(4)(5)(6)(7). Casanova et al (8) asserted that, "The diagnostic boundaries of the behavioral phenotype that define ASD are fairly broad due to the large variability that is observed in symptom types, onset, and severity.…”

“…The efforts for reducing autism heterogeneity-creating prototypical autism, excluding moderate-to-severe autism symptoms, creating subgroups, and increasing sample sizes-have not yet been effective in reducing heterogeneity. Thus, heterogeneity remains an unresolved problem (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17). Moreover, as discussed previously, establishing the unitary DSM-5 ASD diagnosis has not reduced autism heterogeneity.…”

“…Wiggins et al ( 7 ) found that one ASD heterogeneity factor—symptoms of dysregulation including anxiety, depression, aggression, and sleep problems—was responsible for 49–65% of the variance in an ASD sample. They also reported that expressive and receptive language skills were responsible for an additional 15–30% of the variance.…”

“…Morris et al ( 1 ) stated that psychiatric diagnoses “have been reified—seen as “real entities” —when in reality they are not natural kinds” (p. 2). Autism is not a unitary biological entity or natural kind ( 2 ) because individuals diagnosed with autism have many varied and complex biological causes for their symptoms, and vary in symptom patterns, comorbidities, and biomarkers ( 3 – 7 ). Casanova et al ( 8 ) asserted that, “The diagnostic boundaries of the behavioral phenotype that define ASD are fairly broad due to the large variability that is observed in symptom types, onset, and severity.…”

Early measurement of autism risk constructs in the general population: A new factor structure of the First Years Inventory (FYIv3.1) for ages 6–16 months

“…Such findings might be underscored by a recent systematic review (Canu et al, 2021) on non‐social behavioral indicators of ASD in infant siblings, which suggested that non‐social signs appear much ahead of the full manifestation of social impairments. Moreover, these non‐social behavioral markers could be specific for ASD, rather than a general marker of global developmental delay (DD) (Canu et al, 2021; Wiggins et al, 2021). Furthermore, behaviors outside of the social‐communication domain, such as atypical sensory hyper‐and hypo‐reactivity, dysregulation, sensory‐motor repetitions, motor challenges and atypical visual attention may be important to study for their developmental precedence (Baranek et al, 2018; Robertson & Baron‐Cohen, 2017; Sacrey et al, 2014; Thye et al, 2018).…”