Individualized DTI-ALPS Identifies Phase-Specific Glymphatic Dysfunction in Early-Stage Bipolar Disorder
PMC13024597
· 10.3390/biomedicines14030699
Gap Declaration
Recently, one investigation focusing on first-episode, drug-naïve BD patients (mean age ≈ 20 years) analyzed depressive, manic, and mixed phases separately, finding ALPS index reductions specifically in the mixed phase. Together with our findings in early BD-D, these results preliminarily indicate that glymphatic alterations are present in the early stages of BD. However, the specific mood phase in which they occur remains unclear. Although we did not include a mixed-phase subgroup, the use of the iALPS pipeline and the well-balanced BD-D and BD-M samples enabled a robust comparison between depressive and manic phases. In addition, our study extends this evidence by demonstrating that reductions in ALPS indices showed a right-hemispheric predominance.
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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