White Matter Microstructural Alterations in Children with ADHD: Categorical and Dimensional Perspectives.
Studies of brain alterations in children with attention-deficit/hyperactivity disorder (ADHD) have shown heterogeneous results. The aims of the current study were to investigate white matter microstructure in children using both categorical and dimensional definitions of ADHD and to determine the functional consequences of observed alterations. In a large single-site sample of children (aged 8-15 years) with ADHD (n=83) and healthy controls (n=122), we used tract-based spatial statistics on diffusion tensor imaging data to investigate whole-skeleton differences of fractional anisotropy (FA), mean, axial, and radial diffusivity (MD, AD, RD), and mode of anisotropy related to ADHD status (categorical) and symptom severity (dimensional). For categorical differences observed, we analyzed their association with cognitive functioning in working memory and inhibition. Compared with healthy controls, children with ADHD showed decreased FA and increased RD in widespread, overlapping brain regions, mainly in corpus callosum (CC) and major tracts in the left hemisphere. Decreased FA was associated with inhibition performance in the participants with ADHD. Using dimensional definitions, greater hyperactivity/impulsivity symptom severity was associated with higher FA also in widespread regions, mainly in CC and major tracts in the right hemisphere. Our study showed white matter alterations to be related to ADHD status and symptom severity in patients. The coexistence of decreased FA and increased RD in the absence of alterations in MD or AD might indicate altered myelination as a pathophysiological factor in ADHD.
Institute of Mental Health, National Clinical Research Center for Mental Disorders, Peking University Sixth Hospital, Beijing, China.|Key Laboratory of Mental Health, Ministry of Health, Peking University, Beijing, China.|Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands.|Donders Institute for Brain, Cognition and Behavior, Nijmegen, The Netherlands.
Zhao-Min
ZM
Wu
Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands.|Donders Institute for Brain, Cognition and Behavior, Nijmegen, The Netherlands.
Janita
J
Bralten
Institute of Mental Health, National Clinical Research Center for Mental Disorders, Peking University Sixth Hospital, Beijing, China.|Key Laboratory of Mental Health, Ministry of Health, Peking University, Beijing, China.
Qing-Jiu
QJ
Cao
Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands.|Donders Institute for Brain, Cognition and Behavior, Nijmegen, The Netherlands.
Martine
M
Hoogman
Donders Institute for Brain, Cognition and Behavior, Nijmegen, The Netherlands.
Marcel P
MP
Zwiers
Institute of Mental Health, National Clinical Research Center for Mental Disorders, Peking University Sixth Hospital, Beijing, China.|Key Laboratory of Mental Health, Ministry of Health, Peking University, Beijing, China.
Li
L
An
Institute of Mental Health, National Clinical Research Center for Mental Disorders, Peking University Sixth Hospital, Beijing, China.|Key Laboratory of Mental Health, Ministry of Health, Peking University, Beijing, China.
Li
L
Sun
Institute of Mental Health, National Clinical Research Center for Mental Disorders, Peking University Sixth Hospital, Beijing, China.|Key Laboratory of Mental Health, Ministry of Health, Peking University, Beijing, China.
Li
L
Yang
Center for Cognition and Brain Disorders, Hangzhou Normal University; Zhejiang Key Laboratory for Research in Assessment of Cognitive Impairments, Hangzhou, China.
Yu-Feng
YF
Zang
Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands.|Donders Institute for Brain, Cognition and Behavior, Nijmegen, The Netherlands.|Department of Psychiatry, Donders Institute for Brain, Cognition and Behavior, Radboud University Medical Center, Nijmegen, The Netherlands.
Barbara
0000-0003-4375-6572
B
Franke
Institute of Mental Health, National Clinical Research Center for Mental Disorders, Peking University Sixth Hospital, Beijing, China.|Key Laboratory of Mental Health, Ministry of Health, Peking University, Beijing, China.
Yu-Feng
YF
Wang
D000293:Adolescent; D001289:Attention Deficit Disorder with Hyperactivity / Q000473:pathology* / Q000523:psychology*; D001921:Brain / Q000473:pathology* / Q000502:physiology; D002648:Child; D056324:Diffusion Tensor Imaging; D005260:Female; D006801:Humans; D007266:Inhibition, Psychological; D008297:Male; D008570:Memory, Short-Term; D012720:Severity of Illness Index; D066127:White Matter / Q000473:pathology*
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