Cerebral glymphatic system disruptions in methadone maintenance treatment: A multimodal MRI study

Methadone maintenance treatment (MMT) individuals often suffer from multiple complications involving depression, anxiety, and sleep disruption. However, whether cerebral glymphatic system (GS) participates in these neuropsychological aberrances is unknown. This study aims to explore the GS functions using multimodal magnetic resonance imaging (MRI) and to investigate their latent associations with neuropsychological performance.

In this study, a total of 36 MMT patients and 43 healthy controls (HC) were ultimately included. The global blood‑oxygen-level-dependent signals and cerebrospinal fluid (gBOLD-CSF) coupling, diffusion tensor imaging analysis along the perivascular space (DTI-ALPS), white matter free water (WM-FW), and choroid plexus volumes (CPV) were calculated to assess GS function. Fifteen questionnaire scales evaluated depression, anxiety, insomnia, cognition, impulsivity, and craving manifestations. Pearson correlation analyses and multivariate general linear model (GLM) were used to discover GS indices-neuropsychology relationships.

Compared to HC, MMT group showed significantly higher scores in Hamilton Anxiety Scale (HAMA), Hamilton Depression Scale (HAMD), Pittsburgh Sleep Quality Index (PSQI), Barratt-total/attention/no-planning, and Insomnia Severity Index (ISI). The MMT group exhibited significantly lower gBOLD-CSF coupling and higher DTI-ALPS in the right hemisphere (DTI-ALPS(R)) than HC, possibly due to homeostasis imbalance in GS. Lower gBOLD-CSF coupling correlated with higher risk of depression, anxiety, and insomnia symptoms. Moreover, DTI-ALPS(R) was positively related to cognitive function.

Our findings shed light on the pathophysiology of MMT-related complications, demonstrating that deficits in brain waste clearance system are associated with neuropsychological abnormalities.