An analysis of data from five large-scale studies found somewhat lower white matter fractional anisotropy in certain regions of the brain in persons diagnosed with attention deficit hyperactivity disorder (ADHD). Fractional anisotropy is generally considered an indicator of connectivity in the brain. Similar microstructural anomalies were not present for anxiety, mood, or externalizing problems. The study was published in Biological Psychiatry.
Attention deficit hyperactivity disorder or ADHD is one of the most common neurodevelopmental disorders of childhood. Children with ADHD may be prone to acting without thinking about what the results may be, have trouble paying attention, and are generally overactive.
Recently, researchers started seeing ADHD as a disorder of brain connectivity where specific “white matter tracts that form structural connections in the brain underlie disruptions in large-scale brain systems that are tied to symptoms.” The evidence for this concept mostly comes from studies demonstrating differences in markers of brain white matter microstructure associated with ADHD. However, there is little consensus on the exact regions of the brain these differences are located in.
To try to overcome these issues, Gustavo Sudre and his colleagues from the National Human Genome Research Institute and the National Institute of Mental Health in Bethesda analyzed data from five large-scale studies – the Healthy Brain Network (HBN), Adolescent Brain and Cognitive Development (ABCD), Neurobehavioral Clinical Research (NCR), National Consortium on Alcohol and Neurodevelopment in Adolescence (NCANDA), and Human Connectome Project – Developmental (HCP-D).
Altogether, datasets from these studies included data from 6,993 individuals aged between 6 and 18 years and of normal intelligence (IQs over 70). The researchers considered the presence of ADHD traits assessed by a parent/caregiver (Child Behavior Check List, CBCL) and the diagnosis of ADHD as established through diagnostic interviews. Researchers also included results of psychological scales that assess attention problems.
As the primary outcome measure, they used fractional anisotropy “calculated for the brain’s 42 major white matter tracts as defined by the IIT Human Brain Atlas version 5.0.”
“This measure was chosen as it is the most widely used index of microstructure, and it has been the focus of the four meta-analyses of DTI studies in ADHD,” the researchers said.
Results showed that white matter tracts studied differ in their associations with ADHD traits and diagnosis. This means that differences in white matter tracts between participants with and without ADHD were restricted to certain brain regions and not existing in all parts of the brain equally. White matter tracts are bundles of nerve fibers connecting nuclei of the central nervous system and enabling the exchange of nerve impulses between them.
Further analysis showed that both the level of ADHD traits and ADHD diagnosis were associated with “altered microstructure of the inferior longitudinal fasciculi and the left uncinate fasciculus”. The overall size of these differences was small. “White matter tract microstructural anomalies were not as prominently associated with problems related to mood, anxiety or other externalizing problems,” the study authors conclude.
This study used data from multiple groups of people and used a harmonized procedure for taking brain images. In that way, it overcame problems from previous small-scale studies that led to inflated effect sizes and false positive reports. However, authors note that an important limitation is that “the small effect sizes observed limit the clinical utility of this imaging modality in isolation, as such differences cannot reliably distinguish individuals with and without ADHD”.
The study, “A mega-analytic study of white matter microstructural differences across five cohorts of youth with attention deficit hyperactivity disorder”, was authored by Gustavo Sudre, Luke Norman, Marine Bouyssi-Kobar, Jolie Price, Gauri Shastri, and Philip Shaw.
