Emotion dysregulation and right pars orbitalis constitute a neuropsychological pathway to attention deficit hyperactivity disorder

Emotion dysregulation is common in attention deficit hyperactivity disorder (ADHD), which is known to be clinically heterogeneous. However, it remains unclear whether emotion dysregulation represents a neuropsychological pathway to ADHD. Here, using a large population-based cohort (n = 6,053), we show that emotion dysregulation was associated with ADHD symptoms (partial eta² = 0.21) and this persisted after controlling for the cognitive and motivational deficits. Emotion dysregulation mediated the association between smaller surface area of the right pars orbitalis and greater ADHD symptoms at 1-year follow-up, indicating an emotion pathway for ADHD. This pathway was associated with immune responses by both transcriptomic analyses and white blood cell markers. In an independent clinical sample for ADHD (n = 672), the emotion pathway improved the case/control classification accuracy. These findings suggest that emotion dysregulation is a core symptom and route to ADHD, which may not respond to the current pharmacological treatments for ADHD.