Reduced fronto-striatal volume in attention-deficit/hyperactivity disorder in two cohorts across the lifespan

Abstract

Attention-Deficit/Hyperactivity Disorder (ADHD) has been associated with altered brain anatomy in neuroimaging studies. However, small and heterogeneous study samples, and the use of region-of-interest and tissue-specific analyses have limited the consistency and replicability of these effects. We used a data-driven multivariate approach to investigate neuroanatomical features associated with ADHD in two independent cohorts: the Dutch NeuroIMAGE cohort (n = 890, 17.2 years) and the Brazilian IMpACT cohort (n = 180, 44.2 years). Using independent component analysis of whole-brain morphometry images, 375 neuroanatomical components were assessed for association with ADHD. In both discovery (corrected-p = 0.0085) and replication (p = 0.032) cohorts, ADHD was associated with reduced volume in frontal lobes, striatum, and their interconnecting white-matter. Current results provide further evidence for the role of the fronto-striatal circuit in ADHD in children, and for the first time show its relevance to ADHD in adults. The fact that the cohorts are from different continents and comprise different age ranges highlights the robustness of the findings.

Keywords: ADHD; Fronto-striatal; Independent component analysis; Tensor-based morphometry; White matter.

Fig. 1

ICA component associated with ADHD. A. ADHD patients demonstrated reduced loading of a component capturing volume of prefrontal white-matter together with orbitofrontal, striatal, and insular grey-matter (IC z-score > 3.6). The focal area of highest component probability (IC z-score > 8) is depicted on the right, showing orbitofrontal white-matter volume reduction bilaterally. B. Residualized ICA component loading in individuals with and without ADHD in both cohorts. Error bar indicates standard error.

Fig. 2

Age-by-diagnosis interaction A. ICA component with strongest nominal age-by-diagnosis interaction effect. B. Plots of the age-by-diagnosis interaction on ICA component 17 in both cohorts.