Glymphatic-System Function Is Associated with Addiction and Relapse in Heroin Dependents Undergoing Methadone Maintenance Treatment

This study investigates the impact of methadone maintenance treatment (MMT) on the brain glymphatic system (GS) in opioid addiction in China. A total of 51 male MMT patients, 48 demographically matched healthy controls (HCs), and 20 heroin dependents (HDs) were recruited for this study. The GS functioning was assessed using diffusion-tensor-imaging analysis along perivascular spaces (DTI-ALPS index) and the bilateral ALPS divergency (DivALPS). Group differences were analyzed utilizing ANOVA and two-sample t-tests. The relationship between DivALPS and relapse rate was explored using regression analysis. The DTI-ALPS index was significantly higher for the left-side brain than the right side in all three groups. There was a significant difference for the right side (p = 0.0098) between the groups. The MMT and HD groups showed significantly higher DTI-ALPS than the HC group (p = 0.018 and 0.016, respectively). The DivALPS varied significantly among the three groups (p = 0.04), with the HD group showing the lowest and the HC group the highest values. Significant negative relationships were found between relapse count, DivALPS (p < 0.0001, Exp(B) = 0.6047), and age (p < 0.0001, Exp(B) = 0.9142). The findings suggest that MMT may contribute to promoting brain GS recovery in heroin addicts, and modulation of the GS may serve as a potential biomarker for relapse risk, providing insights into novel therapeutic strategies.