Structural brain alterations and their association with cognitive function and symptoms in Attention-deficit/Hyperactivity Disorder families

Wenhao Jiang, Kuaikuai Duan, Kelly Rootes-Murdy, Pieter J. Hoekstra, Catharina A. Hartman, Jaap Oosterlaan, Dirk Heslenfeld, Barbara Franke, Jan Buitelaar, Alejandro Arias-Vasquez, Jingyu Liu, Jessica A. Turner*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


Gray matter disruptions have been found consistently in Attention-deficit/Hyperactivity Disorder (ADHD). The organization of these alterations into brain structural networks remains largely unexplored. We investigated 508 participants (281 males) with ADHD (N = 210), their unaffected siblings (N = 108), individuals with subthreshold ADHD (N = 49), and unrelated healthy controls (N = 141) with an age range from 7 to 18 years old from 336 families in the Dutch NeuroIMAGE project. Source based morphometry was used to examine structural brain network alterations and their association with symptoms and cognitive performance. Two networks showed significant reductions in individuals with ADHD compared to unrelated healthy controls after False Discovery Rate correction. Component A, mainly located in bilateral Crus I, showed a ADHD/typically developing difference with subthreshold cases being intermediate between ADHD and typically developing controls. The unaffected siblings were similar to controls. After correcting for IQ and medication status, component A showed a negative correlation with inattention symptoms across the entire sample. Component B included a maximum cluster in the bilateral insula, where unaffected siblings, similar to individuals with ADHD, showed significantly reduced loadings compared to controls; but no relationship with individual symptoms or cognitive measures was found for component B. This multivariate approach suggests that areas reflecting genetic liability within ADHD are partly separate from those areas modulating symptom severity.

Original languageEnglish
Article number102273
JournalNeuroImage: Clinical
Publication statusPublished - 2020
Externally publishedYes

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