The neurobehavioral, environmental and genetic factors impacting ADHD.

National Human Genome Research Institute

Investigators

Linked publications & trials

Abstract

Our research continues to focus on how attention deficit hyperactivity disorder (ADHD) may impact on brain development. In 2023-2024, we continued its efforts to integrate findings from our NHGRI-based cohort on how brain differences are tied to ADHD with data from other, similar childhood cohorts. Over the past year we completed a large study that using brain imaging data to test a major model of ADHD, as being tied to altered connections between deep brain regions and the cortex. Specifically, we used functional MRI data acquired while the subject is at rest, to examine if ADHD is associated with differences in functional connections between the deep striatum and fronto-cortical regions. We conducted a mega-analysis of six neuroimaging data sets, testing for associations both with ADHD considered as a diagnosis and as a behavioral trait. The main study included 1,696 youths )mean age 10.8 years) with ADHD diagnoses who were compared to 6,737 unaffected individuals. We found youths with ADHD showed greater connectivity between deep striatal regions and temporal, fronto-insular, and supplementary motor regions, as well as between the amygdala and dorsal anterior cingulate cortex, compared with those who did not have ADHD. Similar findings emerged when ADHD traits were considered. The most striking associations centered on the connectivity of the caudate (part of the striatum). Findings were not driven by in-scanner motion and were not shared with commonly comorbid internalizing and externalizing problems. Effect sizes were small (largest peak d, 0.15). The findings from this large-scale mega-analysis support established links with subcortico-cortical circuits, which were robust to potential confounders. However, effect sizes were small, and it seems likely that resting-state subcortico-cortical connectivity can capture only a fraction of the complex pathophysiology of ADHD. These findings add to the emerging consensus that the cross-sectional neural changes detectable by current neuroimaging modalities in a complex phenotype such as ADHD are associated with small effect sizes, making large imaging sample sizes and replication paramount. Publications. PMID 38476041 PMID 38822588.