Estimating the Heritability of Developmental Change in Neural Connectivity, and Its Association With Changing Symptoms of Attention-Deficit/Hyperactivity Disorder

Abstract

BackgroundTwin studies show that age-related change in symptoms of attention-deficit/hyperactivity disorder (ADHD) is heritable. However, we do not know the heritability of the development of the neural substrates underlying the disorder. Here, we estimated the heritability of developmental change in white matter tracts and the brain’s intrinsic functional connectivity using longitudinal data. We further determined associations with change in ADHD symptoms. MethodsThe study reports on 288 children, which included 127 siblings, 19 cousins, and 142 singletons; 150 (52%) had a diagnosis of ADHD (determined by clinician interview with parent); 188 were male. All had two clinical assessments (overall baseline mean age: 9.4 ± 2.4 years; follow-up: 12.5 ± 2.6 years). Diffusion tensor imaging estimated microstructural properties of white matter tracts on 252 participants. Resting-state functional magnetic resonance imaging estimated intrinsic connectivity within and between major brain networks on 226 participants. Total additive genetic heritability (h2) of the annual rate of change in these neural phenotypes was calculated using SOLAR (Sequential Oligogenic Linkage Analysis Routines). ResultsSignificant heritability was found for the rates of change of 6 white matter tract microstructural properties and for change in the connectivity between the ventral attention network and both the cognitive control and dorsal attention networks. Change in hyperactivity-impulsivity was associated with heritable change in white matter tracts metrics and change in the connectivity between the ventral attention and cognitive networks. ConclusionsThe relatively small number of heritable, ADHD-associated developmental neural phenotypes can serve as phenotypes for future gene discovery and understanding.