Neuroimaging Findings in ADHD and the Role of Genetics

Abstract

ADHD is frequently diagnosed in children and adults. The disorder is highly heritable. However, the genetic architecture of ADHD is complex, with multiple genetic variants of individually small effect size contributing to disease in most patients.

In our own studies as well as in the large mega-analyses of the ENIGMA ADHD Working Group, we have investigated the brain substrates of ADHD. We find the disorder to be characterized by delayed sub–cortical and cortical growth of gray matter in childhood, which gradually normalizes in adulthood: sub–cortical volumes as well as cortical thickness and surface area are smaller in children with ADHD, but become indistinguishable from healthy individuals in adulthood. The situation looks different for white matter connectivity: both in childhood and adulthood, widespread differences in the major white matter tracts are found. The pattern of findings suggests that alterations in myelination might lie at the basis of such case-control differences. Since the disorder and many brain structural measures affected in ADHD are highly heritable, we investigated the overlap of genetic risk factors for ADHD with genetic factors involved in brain volume. This resulted in the identification of several genetic variants contributing to disease risk as well as ADHD-related brain phenotype.

In conclusion, we find ADHD to be a disorder of delayed brain maturation in terms of gray matter, but of persistently altered white matter connectivity across the lifespan. Genetic factors influencing both disease risk and brain measures might improve our understanding of disease etiology and persistence.

Disclosure of interest

The author declares that he has no competing interest.