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Related Experiment Video

Updated: Apr 17, 2026

Developing a Rat Model for Bipolar Disorder

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Published on: May 2, 2025

Glymphatic Dysfunction in bipolar disorder: A scoping review and integrative pathophysiological framework.

Zhangyan Shan¹, Qianyu Zhu¹, Shuai Wang¹

¹The Affiliated Mental Health Center of Jiangnan University, Wuxi, Jiangsu, China.

Psychiatry Research

|April 15, 2026

Summary

The brain's glymphatic system, crucial for waste clearance, may be impaired in bipolar disorder (BD). This dysfunction could link stress, immune responses, and cognitive changes in BD patients.

Keywords:

Aquaporin-4 Bipolar disorder Glymphatic dysfunction Lithium Sleep-wake cycle

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Area of Science:

Neuroscience
Neurobiology
Psychiatry

Background:

The glymphatic system clears waste from the brain and is linked to neurological disorders.
Bipolar disorder (BD) is a complex neuropsychiatric condition with unclear underlying mechanisms.

Purpose of the Study:

To review the role of the glymphatic system in bipolar disorder.
To synthesize evidence connecting glymphatic function and BD.
To propose a framework linking glymphatic disruption to BD features.

Main Methods:

Scoping review of existing literature.
Analysis of preliminary neuroimaging data in BD.
Examination of molecular, cellular, and preclinical findings.

Main Results:

Individuals with BD show altered glymphatic indices in neuroimaging.
HPA axis activation, neuroinflammation, and stress may impair glymphatic function via AQP4 pathways.
Lithium may exert therapeutic effects by modulating glymphatic pathways.

Conclusions:

Glymphatic dysfunction is a potential mechanism integrating stress, immune, and cognitive aspects of BD.
Further research is needed to develop glymphatic-informed biomarkers and treatments for BD.