Toward a Revised Nosology for Attention-Deficit/Hyperactivity Disorder Heterogeneity

Attention-deficit/hyperactivity disorder (ADHD) is among the many syndromes in the psychiatric nosology for which etiological signal and clinical prediction are weak. Reducing phenotypic and mechanistic heterogeneity should be useful to arrive at stronger etiological and clinical prediction signals. We discuss key conceptual and methodological issues, highlighting the role of dimensional features aligned with Research Domain Criteria and cognitive, personality, and temperament theory as well as neurobiology. We describe several avenues of work in this area, utilizing different statistical, computational, and machine learning approaches to resolve heterogeneity in ADHD. We offer methodological and conceptual recommendations. Methodologically, we propose that an integrated approach utilizing theory and advanced computational logic to address targeted questions, with consideration of developmental context, can render the heterogeneity problem tractable for ADHD. Conceptually, we conclude that the field is on the cusp of justifying an emotionally dysregulated subprofile in ADHD that may be useful for clinical prediction and treatment testing. Cognitive profiles, while more nascent, may be useful for clinical prediction and treatment assignment in different ways depending on developmental stage. Targeting these psychological profiles for neurobiological and etiological study to capture different pathophysiological routes remains a near-term opportunity. Subtypes are likely to be multifactorial, cut across multiple dimensions, and depend on the research or clinical outcomes of interest for their ultimate selection. In this context parallel profiles based on cognition, emotion, and specific neural signatures appear to be on the horizon, each with somewhat different utilities. Efforts to integrate such cross-cutting profiles within a conceptual dysregulation framework are well underway.