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Brain connectivity associated with ADHD is inheritable

Recent findings identified significant inheritable structural and functional connectivity features associated with ADHD and indicated that shared genetic factors may contribute to phenotypic associations between functional and structural connections.

“There has been limited progress in identifying the specific genes contributing to the established high heritability of attention-deficit/hyperactivity disorder (ADHD). The use of heritable, brain-based phenotypes pertinent to the disorder might accelerate progress in part because they lie closer to genes than the more distal clinical phenotype,” Gustavo Sudre, PhD, of the National Human Genome Research Institute, Bethesda, Md., and colleagues wrote.

To assess structural and functional connections that are heritable and associated with ADHD, researchers evaluated 24 extended multigenerational families with ADHD. Structural connectivity was determined via diffusion tensor imaging of white matter tract microstructure. Functional connectivity was measured with resting-state functional MRI. Findings were confirmed in 52 nuclear families, who had a mean age of 20.9 years at imaging. Multigenerational extended families had a mean age of 30.4 years at imaging.

Microstructural properties of white matter tracts that connected ipsilateral cortical regions and the corpus callosum were significantly heritable, ranging from total additive genetic heritability (P = .0000002) for radial diffusivity of the right superior longitudinal fasciculus to fractional anisotropy of the right inferior fronto-occipital fasciculus (P = .0009).

The right superior longitudinal fasciculus was most strongly associated with ADHD symptoms (P = .003).

Researchers found genetic patterns of functional connectivity in the default mode (P < .002), cognitive control (P < .002) and ventral attention networks (P < .002). Subregions within each network exhibited significant heritable functional connectivity with the rest of that network, according to researchers.

Decreased functional connectivity in the default mode network was associated with more symptoms of hyperactivity/impulsivity (P = .008) and inattention (P = .02).

“Several facets of structural and functional connectivity emerged as significantly heritable within extended families affected by ADHD. A separate cohort of nuclear families confirmed this heritability. For white matter tracts, heritability was found for microstructural features of the association (superior longitudinal fasciculi, inferior fronto-occipital, and uncinate fasciculi) and commissural (corpus callosum), but not for projection tracts (corticospinal tract),” the researchers wrote. “Heritable patterns of functional connectivity were also noted within the default mode, cognitive control, and attention networks. Association with ADHD symptom severity emerged primarily for the heritable facets of the right superior longitudinal fasciculus and the [default mode network]. Finally, cross-modal phenotypic and genetic correlations were found. A white matter tract (inferior fronto-occipital fasciculus) was phenotypically correlated and shared common genetic determinants with the ventral attention network.” – by Amanda Oldt

Disclosure: The researchers report no relevant financial disclosures.