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Female‐specific association of NOS 1 genotype with white matter microstructure in ADHD patients and controls
Author(s) -
Ewijk Hanneke,
Bralten Janita,
Duin Esther D.A.,
Hakobjan Marina,
Buitelaar Jan K.,
Heslenfeld Dirk J.,
Hoekstra Pieter J.,
Hartman Catharina,
Hoogman Martine,
Oosterlaan Jaap,
Franke Barbara
Publication year - 2017
Publication title -
journal of child psychology and psychiatry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.652
H-Index - 211
eISSN - 1469-7610
pISSN - 0021-9630
DOI - 10.1111/jcpp.12742
Subject(s) - fractional anisotropy , impulsivity , psychology , attention deficit hyperactivity disorder , white matter , diffusion mri , genotype , allele , conduct disorder , medicine , genetics , psychiatry , magnetic resonance imaging , biology , gene , radiology
Background The nitric oxide synthase gene ( NOS 1) exon 1f (ex1f) VNTR is a known genetic risk factor for Attention‐Deficit/Hyperactivity Disorder ( ADHD ), particularly in females. NOS 1 plays an important role in neurite outgrowth and may thus influence brain development, specifically white matter ( WM ) microstructure, which is known to be altered in ADHD . The current study aimed to investigate whether NOS 1 is associated with WM microstructure in (female) individuals with and without ADHD . Methods Diffusion Tensor Imaging ( DTI ) scans were collected from 187 participants with ADHD (33% female) and 103 controls (50% female), aged 8–26 years, and NOS 1 ‐ex1f VNTR genotype was determined. Whole‐brain analyses were conducted for fractional anisotropy ( FA ) and mean diffusivity ( MD ) to examine associations between NOS 1 and WM microstructure, including possible interactions with gender and diagnosis. Results Consistent with previous literature, NOS 1 ‐ex1f was associated with total ADHD and hyperactivity‐impulsivity symptoms, but not inattention; this effect was independent of gender. NOS 1 ‐ex1f was also associated with MD values in several major WM tracts in females, but not males. In females, homozygosity for the short allele was linked to higher MD values than carriership of the long allele. MD values in these regions did not correlate with ADHD symptoms. Results were similar for participants with and without ADHD . Conclusions NOS 1 ‐ex1f VNTR is associated with WM microstructure in females in a large sample of participants with ADHD and healthy controls. Whether this association is part of a neurodevelopmental pathway from NOS 1 to ADHD symptoms should be further investigated in future studies.