Assessing glymphatic-associated fluid dynamics in psychiatric disorders: evidence from neuroimaging - a review

Abstract

Although the glymphatic system has been extensively investigated in neurodegenerative diseases, its potential role in psychiatric disorders is only beginning to be recognized. Conditions such as major depressive disorder, schizophrenia, and bipolar disorder frequently exhibit physiological disturbances, including disrupted sleep, neuroinflammation, vascular impairment, and altered astrocytic function, that may modulate glymphatic transport. Recent neuroimaging studies have started to explore these associations. Structural magnetic resonance imaging (MRI) has been used to quantify perivascular space enlargement in depression and schizophrenia. Diffusion-based approaches, including low-b-value diffusion and the diffusion tensor image analysis along the perivascular space (DTI-ALPS) index, have been used to estimate perivascular diffusivity, with some studies linking these measures to symptom severity. Functional MRI metrics such as blood oxygen level-dependent-cerebrospinal fluid (BOLD-CSF) coupling have provided indirect markers of CSF pulsatility, revealing associations with sleep quality and cognition. Positron emission tomography (PET) has been investigated for assessing CSF tracer dynamics and targeting neuroinflammation. While these imaging results are promising, they are often indirect, methodologically heterogeneous, and derived from small samples. This review examines current evidence on glymphatic alterations in psychiatric conditions, describes shared and disorder-specific mechanisms, and assesses how complementary MRI and PET approaches can provide a more integrated understanding of glymphatic function. It also addresses methodological challenges, identifies research gaps, and discusses opportunities to incorporate glymphatic imaging into psychiatric diagnostics, prognosis, and treatment monitoring. The article is intended for researchers and clinicians in psychiatry, neurology, and neuroimaging who are interested in the translational potential of glymphatic research.

Keywords

glymphatic system / psychiatric disorders / neuroimaging / cerebrospinal fluid clearance

Author contributions

Xinlan Zhang (Conceptualization, Data curation, Methodology, Visualization, Writing - original draft, Writing - review & editing), Liana Hatoum (Data curation, Writing - original draft, Writing - review & editing), Jia Ying (Investigation, Visualization, Writing - original draft, Writing - review & editing), Chuan Huang (Conceptualization, Formal Analysis, Investigation, Resources, Supervision, Writing - original draft, Writing - review & editing).

Conflict of Interest Statement

None declared.

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