Specific frontostriatal structural alterations underlie emotional instability but not inattention in ADHD and healthy individuals

Background: ADHD is characterized by emotional dysregulation, such as emotional instability, and by non-emotional symptoms, including inattention. These symptom domains are dimensionally distributed in the general population and are hypothesized to reflect both overlapping and distinct structural and functional features of cortical and subcortical brain networks. Methods: We applied a dimensional symptom approach in a sample of adults with ADHD (n=71) and healthy controls (n=59) to investigate structural brain correlates of inattention and emotional instability, as measured by the Brown Attention-Deficit Disorder Scales. Structural MRI data were analysed to examine cortical and subcortical associations with these symptom dimensions. Performance in an emotional Stroop task was assessed in conjunction with MRI acquisition in a subsample to explore neural correlates of emotion-related cognitive control. Data were collected between 2012 and 2017. Results: Emotional instability was negatively associated with nucleus accumbens volume, independent of inattention symptoms and ADHD diagnosis (β = -0.29, p = 0.016). Additionally, while controlling for inattention symptoms, a negative correlation between emotional instability and cortical surface area was found in a cluster comprising the left dorsolateral prefrontal cortex and right medial/superior frontal cortex. Moreover, cortical thickness in the lateral orbitofrontal cortex was positively associated with performance in the Stroop task in ADHD (r = 0.44, p = 0.027) while being negatively associated in healthy controls (r = -0.40 p = 0.028). Limitations: Medication use within the ADHD group might influence brain-symptom-associations. The cross-sectional design of the study precludes conclusions about causality. Conclusions: These findings suggest that structural alterations in the nucleus accumbens are more strongly related to emotional, rather than attentional symptoms after accounting for their shared variance. Furthermore, altered prefrontal and orbitofrontal morphology may underlie impairments in emotional regulation, supporting the role of frontostriatal circuits in the dimensional expression of emotional instability across clinical and non-clinical populations.