Inhibition-directed multimodal imaging fusion patterns in adults with ADHD and its potential underlying "gene-brain-cognition" relationship.

Aims: Inhibition deficits have been suggested to be a core cognitive impairment in attention-deficit/hyperactivity disorder (ADHD). Exploring imaging patterns and the potential genetic components associated with inhibition deficits would definitely promote our understanding of the neuropathological mechanism of ADHD. This study aims to investigate the multimodal imaging fusion features related to inhibition deficits in adults with ADHD (aADHD) and to make an exploratory analysis of the role of inhibition-related gene, NOS1, on those brain alterations.

Methods: Specifically, multisite canonical correlation analysis with reference plus joint independent component analysis (MCCAR + jICA) was conducted to identify the joint co-varying gray matter volume (GMV) and the functional connectivity (FC) features related to inhibition in 69 aADHD and 44 healthy controls. Then, mediation analysis was employed to detect the relationship among inhibition-related imaging features, NOS1 ex1f-VNTR genotypes, and inhibition.

Results: Inhibition-directed multimodal imaging fusion patterns of aADHD were reduced GMV and FC in inhibition network and increased GMV and FC in default mode network. The results showed a significant indirect effect of NOS1 ex1f-VNTR on inhibition via FC component [effect size = -0.54 (SE = 0.29), 95% CI = -1.16 to -0.01]. In addition, the results indicated a significant indirect effect of GMV on the inhibition via FC component [effect size = 0.43 (SE = 0.23), 95% CI = 0.12 to 1.00].

Conclusion: The findings suggested that reduced GMV and FC in inhibition network and increased GMV and FC in default mode network were jointly responsible for inhibition deficits in aADHD. Both the NOS1 ex1f-VNTR genotypes and GMV might influence the inhibition through the mediation effect of the aforementioned FC (NOS1/GMV Inhibition).