Reduced fronto-striatal volume in ADHD in two cohorts across the lifespan
Renata Basso Cupertino,
Eugenio Horacio Grevet,
Cibele Edom Bandeira,
Felipe Almeida Picon,
Maria Eduarda Tavares,
Daan van Rooij,
Eduardo Schneider Vitola,
Marcel P. Zwiers,
Catharina A Hartman,
Christian F Beckmann,
Jan K. Buitelaar,
Claiton Henrique Dotto Bau,
Posted 02 Oct 2019
bioRxiv DOI: 10.1101/790204
Posted 02 Oct 2019
Neuroimaging studies have associated Attention-Deficit/Hyperactivity Disorder (ADHD) with altered brain anatomy. 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. The present study uses a fully data-driven multivariate approach to investigate alterations in both gray and white matter simultaneously, and capture neuroanatomical features associated with ADHD in two large, independent, demographically different cohorts. Methods: The study comprised two ADHD cohorts with structural magnetic resonance imaging data: the Dutch NeuroIMAGE cohort (n=890, average age 17.2 years, discovery sample) and the Brazilian IMpACT cohort (n=180, average age 44.2 years, cross validation sample). Using independent component analysis of whole-brain morphometry images in the NeuroIMAGE cohort, 375 independent components of neuroanatomical variations were extracted and assessed their association with ADHD. Afterwards, ADHD-associated components were cross validated in the Brazilian IMpACT cohort. Results: In both discovery (corrected-p=0.020) and validation (p=0.033) cohorts, ADHD diagnosis was significantly associated with reduced brain volume in a component mapping to frontal lobes, striatum, and their interconnecting white-matter tracts. The most pronounced case-control differences were localized in white matter adjacent to the orbitofrontal cortex. Conclusion: Independent component analysis is a sensitive approach to uncover neuroanatomical alterations in ADHD and avoid bias attributable to a priori region-of-interest based methods. Current results provide further evidence for the role of the fronto-striatal circuit in ADHD. The fact that the two cohorts are from different continents and comprising different age ranges highlights the robustness of the findings.
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