The structural and fuctional changes of glymphatic system in children with attention-deficit/hyperactivity disorder

Abstract

Abstract Background The enlarged perivascular Virchow-Robin space (VRS), which indicates a glymphatic system alternation, is very common in patients with neurodegenerative diseases. However, assessing those morphological changes in this region by using conventional techniques may be challenging. In this study, we investigated structural and functional changes in the glymphatic system in the treatment-naïve attention-deficit/hyperactivity disorder (ADHD) children by quantitatively measuring the VRS volume using a Diffusion Tensor Image-Analysis Along the Perivascular Space (DTI-ALPS). Methods A total of 47 pediatric ADHD patients and 52 age- and gender-matched typically developing (TD) children were recruited in this prospective study. The VRS volume was calculated using a semi-automated approach in axial T2WI images. Diffusivities along the x, y, and z-axis in the projection, association, and subcortical neural fiber areas on the diffusivity maps were measured. The ALPS-index, a ratio that accentuated water diffusion along the perivascular space, was calculated with: ALPS-index = mean (Dxproj, Dxassoc)/mean (Dyproj, Dzassoc). The Mann-Whitney U test was used to compare the quantitative parameters; Pearson correlation was used to analyze the correlation with clinical symptoms. Results The cerebral VRS volume (mean, 15.514 mL vs.11.702mL) and the VRS volume ratio in the ADHD group were larger than in the TD group (all P < 0.001). The Dxassoc and ALPS-index were significantly smaller in the ADHD group vs. TD group (mean, 1.40 vs.1.59, P < 0.05 after FDR adjustment). Besides, the ALPS-index was related to inattention symptoms of ADHD (r= -0.323, P < 0.05). Conclusions Our study suggests that the glymphatic system alternation may participate in the pathogenesis of ADHD. Moreover, the VRS volume and ALPS index could be used as the metrics for diagnosing ADHD. The study of glymphatic system change may be a new research direction for exploring the mechanisms of psycho-behavioral developmental disorders. Trial registration: This prospective study has been registered online (https://clinicaltrials.gov/ [Identifier: ChiCTR2100048109]).