Integrative profiling of glymphatic dysfunction in adolescent subthreshold depression

Area of Science:

• Neuroimaging
• Adolescent Psychiatry
• Glymphatic System Biology

Background:

• Subthreshold depression (StD) in adolescents is a significant clinical concern with unclear neurobiological underpinnings.
• Glymphatic function, crucial for brain waste clearance, is increasingly implicated in neurological disorders.

Purpose of the Study:

• To investigate multimodal magnetic resonance imaging (MRI) alterations related to glymphatic function in adolescents with StD.
• To identify specific glymphatic biomarkers and their association with clinical symptoms in adolescent StD.

Main Methods:

• Recruited 107 adolescents (71 StD, 36 healthy controls) for multimodal MRI.
• Assessed six glymphatic biomarkers: choroid plexus volume, BOLD-CSF coupling, CSF Hurst exponent, ALPS index, perivascular space volume, and basal forebrain cholinergic nucleus volume.
• Utilized ANCOVA for group comparisons and partial correlations for biomarker-clinical associations, with Mahalanobis distance quantifying multivariate glymphatic profile deviations.

Main Results:

• Adolescents with StD exhibited reduced BOLD-CSF coupling and lower left ALPS index compared to controls.
• Lower left ALPS was associated with increased insomnia severity and self-rated depressive symptoms.
• Lower CSF Hurst exponent correlated with higher PHQ-9 scores; Mahalanobis distance was elevated in StD and strongly associated with PHQ-9 severity.

Conclusions:

• Adolescents with StD display a distinct multivariate glymphatic-related MRI profile characterized by altered BOLD-CSF coupling and reduced ALPS.
• These glymphatic-related MRI alterations may represent a neurobiological feature of adolescent StD.
• Findings support integrating multimodal MRI data for a comprehensive understanding of adolescent StD, rather than relying on single indirect markers.