Cortical alterations associated with lower response to methylphenidate in adults with ADHD

Neurodevelopmental conditions such as attention deficit hyperactivity disorder (ADHD) vary among individuals. For instance, variation exists in clinical response to methylphenidate (MPH) treatment, especially in adults, but the biological basis of this variability is poorly understood. In this longitudinal structural imaging study, we showed that pre-treatment neuroanatomical measures were associated with response to MPH at two months in 60 adults with ADHD. We compared anatomy with that of 23 controls and examined whether differences were enriched for genes linked to MPH dynamics and brain cells. Individuals with ADHD differed from controls in cortical volume and thickness, predominantly in temporo-parietal regions. Treatment non-responders differed from responders and controls in fronto-temporo-parieto-occipital regions and such differences were associated with reduced improvement on inattentive symptoms. These novel findings suggest that variation in neuroanatomy is associated with varying treatment responses. Group differences in cortical thickness were enriched for biologically plausible genes, including those supporting noradrenaline transport, a target of MPH.