Dataset Information

Estimating the Heritability of Structural and Functional Brain Connectivity in Families Affected by Attention-Deficit/Hyperactivity Disorder.

ABSTRACT: Importance:Despite its high heritability, few risk genes have been identified for attention-deficit/hyperactivity disorder (ADHD). Brain-based phenotypes could aid gene discovery. There is a myriad of structural and functional connections that support cognition. Disruption of such connectivity is a key pathophysiologic mechanism for ADHD, and identifying heritable phenotypes within these connections could provide candidates for genomic studies. Objective:To identify the structural and functional connections that are heritable and pertinent to ADHD. Design, Setting, and Participants:Members of extended multigenerational families enriched for ADHD were evaluated. Structural connectivity was defined by diffusion tensor imaging (DTI) of white matter tract microstructure and functional connectivity through resting-state functional magnetic resonance imaging (rsfMRI). Heritability and association with ADHD symptoms were estimated in 24 extended multigenerational families enriched for ADHD (305 members with clinical phenotyping, 213 with DTI, and 193 with rsfMRI data). Findings were confirmed in 52 nuclear families (132 members with clinical phenotypes, 119 with DTI, and 84 with rsfMRI). The study and data analysis were conducted from April 1, 2010, to September 1, 2016. Results:In the 52 nuclear families, 86 individuals (65.2%) were male and the mean (SD) age at imaging was 20.9 (15.0) years; in the 24 multigenerational extended families, 145 individuals (47.5%) were male and mean age at imaging was 30.4 (19.7) years. Microstructural properties of white matter tracts connecting ipsilateral cortical regions and the corpus callosum were significantly heritable, ranging from total additive genetic heritability (h2)?=?0.69 (SE, 0.13; P?=?.0000002) for radial diffusivity of the right superior longitudinal fasciculus to h2?=?0.46 (SE, 0.15; P?=?.0009) for fractional anisotropy of the right inferior fronto-occipital fasciculus. Association with ADHD symptoms was found in several tracts, most strongly for the right superior longitudinal fasciculus (t?=?-3.05; P?=?.003). Heritable patterns of functional connectivity were detected within the default mode (h2?=?0.36; SE, 0.16; cluster level significance, P?

SUBMITTER: Sudre G

PROVIDER: S-EPMC7418037 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature

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Estimating the Heritability of Structural and Functional Brain Connectivity in Families Affected by Attention-Deficit/Hyperactivity Disorder.

Sudre Gustavo G Choudhuri Saadia S Szekely Eszter E Bonner Teighlor T Goduni Elanda E Sharp Wendy W Shaw Philip P

JAMA psychiatry 20170101 1

<h4>Importance</h4>Despite its high heritability, few risk genes have been identified for attention-deficit/hyperactivity disorder (ADHD). Brain-based phenotypes could aid gene discovery. There is a myriad of structural and functional connections that support cognition. Disruption of such connectivity is a key pathophysiologic mechanism for ADHD, and identifying heritable phenotypes within these connections could provide candidates for genomic studies.<h4>Objective</h4>To identify the structural ...[more]

PMID: 27851842

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Project description:Intra-subject variability (ISV) is the most consistent behavioral deficit in Attention Deficit Hyperactivity Disorder (ADHD). ISV may be associated with networks involved in sustaining task control (cingulo-opercular network: CON) and self-reflective lapses of attention (default mode network: DMN). The current study examined whether connectivity supporting attentional control is atypical in children with ADHD. Group differences in full-brain connection strength and brain-behavior associations with attentional control measures were examined for the late-developing CON and DMN in 50 children with ADHD and 50 typically-developing (TD) controls (ages 8-12 years). Children with ADHD had hyper-connectivity both within the CON and within the DMN. Full-brain behavioral associations were found for a number of between-network connections. Across both groups, more anti-correlation between DMN and occipital cortex supported better attentional control. However, in the TD group, this brain-behavior association was stronger and occurred for a more extensive set of DMN-occipital connections. Differential support for attentional control between the two groups occurred with a number of CON-DMN connections. For all CON-DMN connections identified, increased between-network anti-correlation was associated with better attentional control for the ADHD group, but worse attentional control in the TD group. A number of between-network connections with the medial frontal cortex, in particular, showed this relationship. Follow-up analyses revealed that these associations were specific to attentional control and were not due to individual differences in working memory, IQ, motor control, age, or scan motion. While CON-DMN anti-correlation is associated with improved attention in ADHD, other circuitry supports improved attention in TD children. Greater CON-DMN anti-correlation supported better attentional control in children with ADHD, but worse attentional control in TD children. On the other hand, greater DMN-occipital anti-correlation supported better attentional control in TD children.

Dataset Information

Estimating the Heritability of Structural and Functional Brain Connectivity in Families Affected by Attention-Deficit/Hyperactivity Disorder.

Publications

Estimating the Heritability of Structural and Functional Brain Connectivity in Families Affected by Attention-Deficit/Hyperactivity Disorder.

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