Brain alterations in adult ADHD: effects of gender, treatment and comorbid depression

Children with attention-deficit/hyperactivity disorder (ADHD) have smaller volumes of total brain matter and subcortical regions, but it is unclear whether these represent delayed maturation or persist into adulthood. We performed a structural MRI study in 119 adult ADHD patients and 107 controls and investigated total gray and white matter and volumes of accumbens, caudate, globus pallidus, putamen, thalamus, amygdala and hippocampus. Additionally, we investigated effects of gender, stimulant treatment and history of major depression (MDD). There was no main effect of ADHD on the volumetric measures, nor was any effect observed in a secondary voxel-based morphometry (VBM) analysis of the entire brain. However, in the volumetric analysis a significant gender by diagnosis interaction was found for caudate volume. Male patients showed reduced right caudate volume compared to male controls, and caudate volume correlated with hyperactive/impulsive symptoms. Furthermore, patients using stimulant treatment had a smaller right hippocampus volume compared to medication-naïve patients and controls. ADHD patients with previous MDD showed smaller hippocampus volume compared to ADHD patients with no MDD. While these data were obtained in a cross-sectional sample and need to be replicated in a longitudinal study, the findings suggest that developmental brain differences in ADHD largely normalize in adulthood. Reduced caudate volume in male patients may point to distinct neurobiological deficits underlying ADHD in the two genders. Smaller hippocampus volume in ADHD patients with previous MDD is consistent with neurobiological alterations observed in MDD.