Affective-cognitive-behavioral heterogeneity of Attention-Deficit/Hyperactivity Disorder (ADHD): Emotional dysregulation as a sentinel symptom differentiating “ADHD-simplex” and “ADHD-complex” syndromes?

Current DSM and ICD classifications of Attention-Deficit/Hyperactivity Disorder (ADHD) exclude emotional dysregulation (ED) in their diagnostic criteria, despite ED symptoms frequently co-occurring in ADHD and likely sharing common neurobiological substrates. In this study, we examined whether consideration of ED symptoms could delineate more informative "ADHD+ED" subphenotypes.4106 children with ADHD were recruited. ED and inattentive (IA) and hyperactive/impulsive (HI) symptoms were profiled using latent class analyses (LCA). The derived latent class (LC) subphenotypes were evaluated and validated in relation to comorbidity patterns, executive functions, and functional impairments.Five LC subphenotypes with ED symptoms were identified: IA/HI + ED profile (LC1); HI + ED profile (LC2); IA + ED profile (LC3); IA/HI profile (LC4); and IA profile (LC5). Cross-validation of the LCA model using support vector machine analysis confirmed 83% accuracy. ED positive (ED+ve) subphenotypes were associated with higher rates of oppositional defiant disorder, mood disorders, anxiety disorders, as well as more severe autistic traits and sluggish cognitive tempo symptoms. Higher rates of ecological executive functioning impairments (BRIEF ratings) were found among ED+ve subphenotypes (though no differences were detected by laboratory-based measures). Functional impairments were also more severe among participants with ED+ve subphenotypes.The data for our LCA were cross-sectional and based primarily on parent ratings.Our classification model has parcellated IA, HI, and ED symptoms into novel informative subphenotypes. These classifications provide preliminary evidence that ED symptoms could serve as sentinel features to identify a potential "ADHD-complex" syndrome, which demarcates a more pervasive condition of greater severity, complexity, and impairment.