Alterations in the DTI-ALPS index and choroid plexus volume are associated with symptom severity in children with tic disorders

Tic disorders (TD) are common neurodevelopmental conditions characterized by motor and vocal tics. The glymphatic system, which contributes to brain fluid exchange and metabolic waste transport, has not been systematically examined in pediatric tic disorders. In this case–control study, 86 children with tic disorders (Tourette syndrome, n = 38; chronic tic disorder, n = 31; provisional tic disorder, n = 17) and 82 age- and sex-matched healthy controls underwent clinical assessments, magnetic resonance imaging, and blood sampling. Glymphatic surrogate markers were assessed using diffusion tensor imaging analysis along the perivascular space (DTI-ALPS index) and standardized choroid plexus (CP) volume. Tic severity was evaluated using the Yale Global Tic Severity Scale (YGTSS). Multivariable regression and mediation analyses were performed to examine associations among glymphatic markers, clinical features, and inflammation. Compared with healthy controls, children with tic disorders exhibited a significantly lower DTI-ALPS index and a larger choroid plexus volume (both P < 0.001). The two glymphatic surrogate markers were inversely correlated (r = − 0.48, P < 0.001). In multivariable logistic regression analyses, both markers remained independently associated with TD, including lower DTI-ALPS index (OR = 1.89, 95% CI: 1.25–2.86; P = 0.003) and higher choroid plexus volume (OR = 1.62, 95% CI: 1.10–2.40; P = 0.015). Lower DTI-ALPS index and higher choroid plexus volume were consistently associated with greater tic severity across multivariable models (all P ≤ 0.05). Mediation analyses indicated that IL-6 statistically accounted for part of the association between DTI-ALPS index and tic severity (indirect effect = − 0.13, 95% CI: −0.22 to − 0.05), accounting for 31.71% of the total effect, while anxiety symptoms demonstrated a smaller exploratory mediation effect (17.02%). Children with tic disorders exhibit alterations in functional and structural glymphatic surrogate markers associated with tic severity and multiple accompanying clinical and biological phenotypes. Further longitudinal and mechanistic studies are warranted to clarify temporal relationships and underlying biological pathways.