title: White matter microstructure and the variable adult outcome of childhood attention deficit hyperactivity disorder.
abstract: Changes in cerebral cortical anatomy have been tied to the clinical course of attention deficit hyperactivity disorder (ADHD). We now ask if alterations in white matter tract microstructure are likewise linked with the adult outcome of childhood ADHD. Seventy-five young adults, 32 with ADHD persisting from childhood and 43 with symptom remission were contrasted against 74 never-affected comparison subjects. Using diffusion tensor imaging, we defined fractional anisotropy, a metric related to white matter microstructure, along with measures of diffusion perpendicular (radial) and parallel (axial) to the axon. Analyses were adjusted for head motion, age and sex, and controlled for multiple comparisons and medication history. Tract-based analyses showed that greater adult inattention, but not hyperactivity-impulsivity, was associated with significantly lower fractional anisotropy in the left uncinate (standardized β=-0.37, t=3.28, p=0.002) and inferior fronto-occipital fasciculi (standardized β=-0.37, t=3.29, p=0.002). The ADHD group with symptoms persisting into adulthood had significantly lower fractional anisotropy than the never-affected controls in these tracts, differences associated with medium to large effect sizes. By contrast, the ADHD group that remitted by adulthood did not differ significantly from controls. The anomalies were found in tracts that connect components of neural systems pertinent to ADHD, such as attention control (inferior fronto-occipital fasciculus) and emotion regulation and the processing of reward (the uncinate fasciculus). Change in radial rather than axial diffusivity was the primary driver of this effect, suggesting pathophysiological processes including altered myelination as future targets for pharmacological and behavioral interventions.
authors.affiliation: 1] Section on Neurobehavioral Clinical Research, Social and Behavioral Research Branch, National Human Genome Research Institute, Bethesda, MD, USA [2] Intramural Program of the National Institute of Mental Health, Bethesda, MD, USA.
authors.forename: Philip
authors.initials: P
authors.lastname: Shaw
authors.affiliation: Section on Neurobehavioral Clinical Research, Social and Behavioral Research Branch, National Human Genome Research Institute, Bethesda, MD, USA.
authors.forename: Gustavo
authors.initials: G
authors.lastname: Sudre
authors.affiliation: Section on Neurobehavioral Clinical Research, Social and Behavioral Research Branch, National Human Genome Research Institute, Bethesda, MD, USA.
authors.forename: Amy
authors.initials: A
authors.lastname: Wharton
authors.affiliation: Section on Neurobehavioral Clinical Research, Social and Behavioral Research Branch, National Human Genome Research Institute, Bethesda, MD, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Weingart
authors.affiliation: Intramural Program of the National Institute of Mental Health, Bethesda, MD, USA.
authors.forename: Wendy
authors.initials: W
authors.lastname: Sharp
authors.affiliation: NIH MRI Research Facility/National Institute of Neurological Diseases and Stroke/National Institutes of Health, Bethesda, MD, USA.
authors.forename: Joelle
authors.initials: J
authors.lastname: Sarlls
mesh_terms: D016880:Anisotropy; D001288:Attention; D001289:Attention Deficit Disorder with Hyperactivity / Q000175:diagnosis / Q000473:pathology*; D016022:Case-Control Studies; D056324:Diffusion Tensor Imaging; D005260:Female; D006801:Humans; D007175:Impulsive Behavior; D008297:Male; D066127:White Matter / Q000473:pathology*; D055815:Young Adult