Cortical Predictors of Symptom Severity and Treatment Response in Adults with Attention-Deficit/Hyperactivity Disorder

Attention-Deficit/Hyperactivity Disorder (ADHD) in adulthood presents itself with substantial heterogeneity in clinical presentation and treatment response, a complexity that constrains coherent delineation of its neurobiological mechanisms. In response to these considerations, this dissertation sought to identify cortical predictors of symptom severity and treatment variability in adults with ADHD. Surface-based morphometric analyses were performed on neuroimaging data from the Comparison of Methylphenidate and Psychotherapy in Adult ADHD Study, employing the threshold-free cluster enhancement approach within the Computational Anatomy Toolbox, as implemented in Statistical Parametric Mapping in the MATLAB environment. The first study demonstrated that greater inattention severity was associated with reduced cortical gyrification alongside increased cortical thickness and -complexity within regions subserving attentional regulation and self-related processing. The second study linked greater pre-treatment cortical gyrification in the left prefrontal cortex to global symptom improvement, suggesting prefrontal folding complexity as a structural correlate of neuroplastic capacity and therapeutic responsiveness. The third study complemented the preceding findings by showing that greater pre-treatment sulcal depth in temporo-parietal regions also predicted enhanced treatment response, with some associations further moderated by genetic susceptibility for ADHD and shared psychiatric risk. Taken together, the findings presented in this dissertation converge on a multidimensional account of ADHD in adulthood, wherein enduring symptoms and differential treatment outcomes reflect a complex interplay between neurodevelopmental organisation and genetic susceptibility expressed in distinct clinical symptom profiles with variable treatment outcomes.