Individualized DTI-ALPS Identifies Phase-Specific Glymphatic Dysfunction in Early-Stage Bipolar Disorder
PMC13024597
· 10.3390/biomedicines14030699
Gap Declaration
Taken together, the ALPS index emerges as a promising biomarker for glymphatic impairment in early-stage BD. However, methodological heterogeneity and cohort differences across existing studies preclude definitive conclusions. Furthermore, while the observed right-hemispheric reduction aligns with prior evidence of right-sided vulnerability in BD-D, it is important to emphasize that this finding emerged at a trend level and requires further confirmation. Future longitudinal and age-stratified studies are needed to delineate the developmental trajectory of glymphatic function and its phase-specific feature in early BD. A large cohort of young adults strengthens our study, however, several limitations still warrant consideration.
Abstract
Background: The glymphatic system, essential for brain waste clearance and neuroimmune regulation, remains underexplored in the context of bipolar disorder (BD) among young populations. Methods: Using diffusion tensor image analysis along the perivascular space (DTI-ALPS), we compared ALPS indices derived from the conventional FSL-based (cFSL) pipeline with those from the individualized ALPS (iALPS) pipeline. A cohort of young adults comprising 77 individuals with BD and 289 healthy controls was analyzed to evaluate methodological consistency and to identify disorder-specific alterations in glymphatic function. Results: The two pipelines showed only moderate agreement (Lin’s concordance correlation coefficient = 0.52–0.60), suggesting that differences in ROI placement strategies significan…
Conclusions / Discussion
4. Discussion The present study produced two principal findings regarding the assessment of glymphatic function in young adults with BD in different stages. First, we observed moderate concordance between the cFSL and iALPS pipelines for computing the ALPS index. Second, while the cFSL pipeline showed no group-level alterations, the iALPS pipeline revealed a trend-level reduction in the ALPS index in BD-D patients, particularly in the right hemisphere. These findings highlight the variability in methodologies for assessing glymphatic function and emphasize that the chosen analytic approach can significantly affect the detection of subtle physiological changes in psychiatric populations. The difference in methodology between the two pipelines raises an important issue in DTI-ALPS research. Manual ROI placement in the original ALPS method introduces inter-rater variability and poor reproducibility. Even slight errors in ROI placement can significantly compromise the comparability of findings across studies. Template-based approaches, such as the cFSL pipeline we used, mitigate operator bias by registering data to standardized spaces and applying predefined coordinates, with refinemen…
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Structural Hole
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Technique originates in criminal justice; functional analogues in psychology, epidemiology literature are absent.
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