Autism spectrum disorder shares many symptoms with other mental health disorders, and comorbid disorders such as mood and anxiety disorders are common, making the diagnostic process challenging. We aimed to explore the diagnostic accuracy of two standard autism spectrum disorder diagnostic instruments and to identify those behavioral items that best differentiate between autism spectrum disorder and mood and anxiety disorder in a naturalistic sample of patients utilizing autism spectrum disorder specialist services. The study included data of 847 participants (5–65 years of age, n = 586 with autism spectrum disorder, n = 261 with mood and anxiety disorder) all evaluated with the Autism Diagnostic Observation Schedule in the context of the diagnostic process. Data of the Autism Diagnostic Interview–Revised were available for 428 participants (5–51 years of age, n = 367 with autism spectrum disorder, n = 61 with mood and anxiety disorder). By means of binominal logistic regressions and an ensemble feature selection, we identified a subset of items that best differentiated between autism spectrum disorder and mood and anxiety disorder. Overall, the results indicate that a combination of communicational deficits and unusual and/or inappropriate social overtures differentiates autism spectrum disorder and mood and anxiety disorder. Aspects of social cognition are also relevant. Limitations of the current study and implications for research and practice are discussed. Lay abstract Symptoms of mood and anxiety disorders overlap with symptoms of autism spectrum disorder, making the diagnostic process challenging. This study found that a combination of communicational deficits and unusual and/or inappropriate social overtures facilitates differentiation between autism spectrum disorder and mood and anxiety disorders. Furthermore, the results confirm the essential need of a behavioral observation with the Autism Diagnostic Observation Schedule in combination with a full Autism Diagnostic Interview–Revised to support diagnostic decisions.

Autism spectrum disorder (ASD) might be conceptualized as an essentially dimensional, categorical, or hybrid model. Yet, current empirical studies are inconclusive and the latent structure of ASD has explicitly been examined only in a few studies. The aim of our study was to identify and discuss the latent model structure of behavioral symptoms related to ASD and to address the question of whether categories and/or dimensions best represent ASD symptoms. We included data of 2920 participants (1–72 years of age), evaluated with the Autism Diagnostic Observation Schedule (Modules 1–4). We applied latent class analysis, confirmatory factor analysis, and factor mixture modeling and evaluated the model fit by a combination of criteria. Based on the model selection criteria, the model fits, the interpretability as well as the clinical utility we conclude that the hybrid model serves best for conceptualization and assessment of ASD symptoms. It is both grounded in empirical evidence and in clinical usefulness, is in line with the current classification system (DSM-5) and has the potential of being more specific than the dimensional approach (decreasing false positive diagnoses).