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Individualized DTI-ALPS Identifies Phase-Specific Glymphatic Dysfunction in Early-Stage Bipolar Disorder.

Xiaoxi Zhao1,2, Mingli Li3, Qiang Wang3

  • 1Affiliated Mental Health Center & Hangzhou Seventh People's Hospital, Zhejiang University School of Medicine, Hangzhou 310013, China.

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|March 28, 2026
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Summary
This summary is machine-generated.

Glymphatic system function may be impaired in bipolar disorder (BD) during depressive episodes, particularly in young adults. An individualized analysis pipeline (iALPS) shows promise for detecting these subtle, state-specific brain changes.

Keywords:
DTI-ALPSbipolar disorderglymphatic systemindividualized ALPS pipeline

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Area of Science:

  • Neuroimaging
  • Neuroscience
  • Psychiatry

Background:

  • The glymphatic system is crucial for brain waste clearance and neuroimmune regulation.
  • Its role in young adults with bipolar disorder (BD) is understudied.
  • Glymphatic dysfunction may contribute to the pathophysiology of psychiatric disorders.

Purpose of the Study:

  • To compare two analytical pipelines for glymphatic system assessment using diffusion tensor image analysis along the perivascular space (DTI-ALPS).
  • To investigate glymphatic function alterations in young adults with BD, differentiating between illness states.
  • To evaluate the sensitivity of individualized versus conventional analysis methods.

Main Methods:

  • Employed diffusion tensor image analysis along the perivascular space (DTI-ALPS) in 77 young adults with BD and 289 healthy controls.
  • Compared the conventional FSL-based (cFSL) pipeline with an individualized ALPS (iALPS) pipeline for calculating ALPS indices.
  • Assessed methodological consistency and identified disorder-specific glymphatic alterations.

Main Results:

  • The cFSL and iALPS pipelines exhibited moderate agreement, highlighting the impact of ROI placement on ALPS estimation.
  • The iALPS pipeline revealed a trend towards reduced ALPS index in BD patients during depressive episodes, especially in the right hemisphere (p=0.036).
  • No significant glymphatic changes were found in early-stage BD or with the cFSL pipeline.

Conclusions:

  • Glymphatic dysfunction in psychiatric disorders appears to be illness-phase specific.
  • The iALPS pipeline offers enhanced sensitivity for detecting subtle, state-related brain changes compared to conventional methods.
  • This methodological advancement supports future research into glymphatic function in psychiatric disorder pathophysiology.