Inattention and Reaction time Variability are Linked to Ventromedial Prefrontal Volume in Adolescents

Abstract Background Neuroimaging studies of attention-deficit/hyperactivity disorder (ADHD) have most commonly reported volumetric abnormalities in the basal ganglia, cerebellum, and prefrontal cortices. Few studies have examined the relationship between ADHD symptomatology and brain structure in population-based samples. Herein, we investigate the relationship between dimensional measures of ADHD symptomatology, brain structure, and reaction time variability—an index of lapses in attention. We also test for associations between brain structural correlates of ADHD symptomatology and maps of dopaminergic gene expression. Methods Psychopathology and imaging data were available for 1,538 youths. Parent ratings of ADHD symptoms were obtained using the Development and Well-Being Assessment (DAWBA) and the Strengths and Difficulties Questionnaire (SDQ). Self-reports of ADHD symptomatology were assessed using the youth version of the SDQ. Reaction time variability was available in a subset of participants. For each measure, whole brain voxel-wise regressions with gray matter volume (GMV) were calculated. Results Parent ratings of ADHD symptoms (DAWBA and SDQ), adolescent self-reports of ADHD symptoms on the SDQ, and reaction time variability were each negatively associated with GMV in an overlapping region of the ventromedial prefrontal cortex (vmPFC). Maps of DRD1 and DRD2 gene expression were associated with brain structural correlates of ADHD symptomatology. Conclusions This is the first study to reveal relations between vmPFC structure and multi-informant measures of ADHD symptomatology in a large population-based sample of adolescents. Our results indicate that vmPFC structure is a biomarker for ADHD symptomatology. These findings extend previous research implicating the default mode network and dopaminergic dysfunction in ADHD.