White matter microstructure is associated with hyperactive/inattentive symptomatology and polygenic risk for attention-deficit/hyperactivity disorder in a population-based sample of adolescents.
Adolescent
Anisotropy
Attention
Attention Deficit Disorder with Hyperactivity
/ diagnostic imaging
Brain
/ diagnostic imaging
Cerebral Cortex
/ diagnostic imaging
Child
Female
Humans
Male
Multifactorial Inheritance
Neural Pathways
/ diagnostic imaging
Organ Size
Prefrontal Cortex
/ diagnostic imaging
Risk Assessment
White Matter
/ diagnostic imaging
White People
/ genetics
Journal
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
ISSN: 1740-634X
Titre abrégé: Neuropsychopharmacology
Pays: England
ID NLM: 8904907
Informations de publication
Date de publication:
08 2019
08 2019
Historique:
received:
23
12
2018
accepted:
30
03
2019
revised:
24
02
2019
pubmed:
6
4
2019
medline:
18
3
2020
entrez:
6
4
2019
Statut:
ppublish
Résumé
Few studies have investigated the link between putative biomarkers of attention-deficit/hyperactivity disorder (ADHD) symptomatology and genetic risk for ADHD. To address this, we investigate the degree to which ADHD symptomatology is associated with white matter microstructure and cerebral cortical thickness in a large population-based sample of adolescents. Critically, we then test the extent to which multimodal correlates of ADHD symptomatology are related to ADHD polygenic risk score (PRS). Neuroimaging, genetic, and behavioral data were obtained from the IMAGEN study. A dimensional ADHD composite score was derived from multi-informant ratings of ADHD symptomatology. Using tract-based spatial statistics, whole brain voxel-wise regressions between fractional anisotropy (FA) and ADHD composite score were calculated. Local cortical thickness was regressed on ADHD composite score. ADHD PRS was based on a very recent genome-wide association study, and calculated using PRSice. ADHD composite score was negatively associated with FA in several white matter pathways, including bilateral superior and inferior longitudinal fasciculi (p < 0.05, corrected). ADHD composite score was negatively associated with orbitofrontal cortical thickness (p < 0.05, corrected). The ADHD composite score was correlated with ADHD PRS (p < 0.001). FA correlates of ADHD symptomatology were significantly associated with ADHD PRS, whereas cortical thickness correlates of ADHD symptomatology were unrelated to ADHD PRS. Variation in hyperactive/inattentive symptomatology was associated with white matter microstructure, which, in turn, was related to ADHD PRS. Results suggest that genetic risk for ADHD symptomatology may be tied to biological processes affecting white matter microstructure.
Identifiants
pubmed: 30952157
doi: 10.1038/s41386-019-0383-y
pii: 10.1038/s41386-019-0383-y
pmc: PMC6784993
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1597-1603Subventions
Organisme : NIMH NIH HHS
ID : L40 MH108486
Pays : United States
Organisme : Medical Research Council
ID : MR/R00465X/1
Pays : United Kingdom
Organisme : MRF
ID : MRF_MRF-058-0004-RG-DESRI
Pays : United Kingdom
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