Transdiagnostic Behavioral Phenotypes and Comorbid Gastrointestinal Symptoms in Neurodevelopmental Disorders: An...

Neurodevelopmental disorders (NDD), including autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD), have heterogeneous behavioral phenotypes and substantial symptom overlap. Identifying transdiagnostic subgroups may help clarify this heterogeneity. This study aimed to identify behavior-based subgroups of children with NDD and explore links between gastrointestinal (GI) symptoms and behavioral symptoms. Using data from the Province of Ontario Neurodevelopmental Disorders (POND) network, we applied a heterogeneous mixture model (HMM) to behavioral data from 1716 participants, including typically developing (TD, n = 210), ASD (n = 747), and ADHD (n = 759) and identified six distinct clusters. Five of the clusters included individuals with TD, ADHD, and ASD diagnoses. The remaining cluster exhibited the most severe behavior phenotype and was exclusively ADHD and ASD participants. Notably, GI symptoms were significantly more prevalent in the cluster with the most severe behavioral profile (χ² (5) = 64.4, p < 0.0001), which is comparable to previous reports linking GI symptoms to more severe clinical symptoms in NDD. These findings emphasize the importance of considering behavioral dimensions over diagnostic labels to identify NDD subgroups. Further research that focuses on signaling pathways of the gut-brain axis will help understand the biological mechanisms that contribute to individual differences in behavioral profiles in NDDs.