Impaired glymphatic clearance in schizophrenia

According to the model of the glymphatic system, the clearance of waste products from the brain is dependent on the directed flow of fluid across different compartments in the brain and associated lymphatic vessels. The coupling between the coherent global grey matter activity (gGM-activity) and cerebrospinal fluid movement (gGM-CSF-coupling) is thought to drive glymphatic fluid movement in humans. Since gGM-coherence is severely impaired in patients with schizophrenia, the glymphatic system might be impaired in the disorder. Therefore, we hypothesized aberrant glymphatic function in schizophrenia.Twenty-six patients with schizophrenia and 24 healthy controls were assessed by both cognitive testing and simultaneous PET-MRI, including 18F-DOPA-PET, resting-state fMRI, and FLAIR-MRI. As proxies for glymphatic function, we used global GM-CSF-coupling assessed by Pearson’s correlation between the fMRI signal time courses from gGM and CSF of the fourth ventricle, clearance rate of the 18F-DOPA-tracer from the lateral ventricles and the volumes of perisinusoidal meningeal lymphatic vessels (MLVs) from FLAIR scans, based on deep-neural-network segmentations.Compared to healthy controls, patients showed lower gGM-CSF-coupling, lower clearance rate of PET-tracer from the lateral ventricles, and larger MLVs in the anterior part of the superior sagittal sinus. Moreover, we found a correlation between these measures in patients. Importantly, reduced cognitive speed and executive functioning were linked with PET-based tracer clearance and gGM-CSF-coupling.Results demonstrate an impairment of glymphatic clearance in patients with schizophrenia, which is associated with cognitive symptoms.