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. 2021 Mar 1;89(5):443-450.
doi: 10.1016/j.biopsych.2020.06.007. Epub 2020 Jun 13.

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

Gustavo Sudre  1 , Marine Bouyssi-Kobar  1 , Luke Norman  1 , Wendy Sharp  2 , Saadia Choudhury  1 , Philip Shaw  3
Affiliations

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

Gustavo Sudre et al. Biol Psychiatry. .

Abstract

Background: Twin 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.

Methods: The 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).

Results: Significant 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.

Conclusions: The relatively small number of heritable, ADHD-associated developmental neural phenotypes can serve as phenotypes for future gene discovery and understanding.

Keywords: ADHD; Connectome; DTI; Developmental; Heritability; Longitudinal; Resting-state fMRI.

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Conflict of interest statement

The authors report no biomedical financial interests or potential conflicts of interest.

Figures

Figure 1.
Figure 1.
Participants. (A) Each child is shown as a line, connecting the two ages of their assessment. Each family is shown in the same color. (B) The data from one family with 4 siblings is shown.
Figure 2.
Figure 2.
Heritability of white matter tracts. Heritability of age-related change in axial diffusivity (AD) and radial diffusivity (RD) of white matter tracts is shown (all significant at false discovery rate q = .05).
Figure 3.
Figure 3.
Heritability of functional connectivity. Heritability of rate of change of connectivity within and between all networks is shown.
Figure 4.
Figure 4.
Associations between change in hyperactive-impulsive symptoms with age. (A) Association with change in axial diffusivity (AD) of the forceps minor; (B) association with change in connectivity between the cognitive control network and ventral attention network (VAN).
See this image and copyright information in PMC

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