Brain gray matter deficits at 33-year follow-up in adults with attention-deficit/hyperactivity disorder established in childhood

Context: Volumetric studies have reported relatively decreased cortical thickness and gray matter volumes in adults with attention-deficit/hyperactivity disorder (ADHD) whose childhood status was retrospectively recalled. We present, to our knowledge, the first prospective study combining cortical thickness and voxel-based morphometry in adults diagnosed as having ADHD in childhood. Objectives: To test whether adults with combinedtype childhood ADHD exhibit cortical thinning and decreased gray matter in regions hypothesized to be related to ADHD and to test whether anatomic differences are associated with a current ADHD diagnosis, including persistent vs remitting ADHD. Design: Cross-sectional analysis embedded in a 33-year prospective follow-up at a mean age of 41.2 years. Setting: Research outpatient center. Participants: We recruited probands with ADHD from a cohort of 207 white boys aged 6 to 12 years. Male comparison participants (n=178) were free of ADHD in childhood. Weobtained magnetic resonance images in 59 probands and 80 comparison participants (28.5% and 44.9% of the original samples, respectively). Main Outcome Measures: Whole-brain voxel-based morphometry and vertexwise cortical thickness analyses. Results: The cortex was significantly thinner in ADHD probands than in comparison participants in the dorsal attentional network and limbic areas (false discovery rate <0.05, corrected). In addition, gray matter was significantly decreased in probands in the right caudate, right thalamus, and bilateral cerebellar hemispheres. Probands with persistent ADHD (n=17) did not differ significantly from those with remitting ADHD (n=26) (false discovery rate <0.05). At uncorrected P <.05, individuals with remitting ADHD had thicker cortex relative to those with persistent ADHD in the medial occipital cortex, insula, parahippocampus, and prefrontal regions. Conclusions: Anatomic gray matter reductions are observable in adults with childhood ADHD, regardless of the current diagnosis. The most affected regions underpin top-down control of attention and regulation of emotion and motivation. Exploratory analyses suggest that diagnostic remission may result from compensatory maturation of prefrontal, cerebellar, and thalamic circuitry.