Transdiagnostic Reductions in Glymphatic-Related Perivascular Diffusion Across Psychiatric Disorders: A Systematic Review and Meta-analysis.
Abstract
Background
The glymphatic system, a perivascular pathway supporting cerebrospinal and interstitial fluid exchange and clearance, has been implicated in neurodegenerative and psychiatric disorders. Diffusion tensor imaging along the perivascular space (DTI-ALPS) provides a non-invasive proxy for glymphatic-related processes, yet its role in psychiatric conditions remains uncertain.
Methods
Following PRISMA guidelines, we systematically searched PubMed, PsycNET, and Embase for articles published up to September 25th, 2025. The protocol was pre-registered in PROSPERO (CRD420251155430). Studies reporting diffusion-based indices of glymphatic function in psychiatric populations were included. Standardised mean differences (Hedges' g) were calculated for patient-control comparisons and pooled using random-effects models. Heterogeneity, methodological moderators, and risk of bias were assessed.
Results
Thirty-two studies met inclusion criteria for the systematic review, covering major psychiatric groups including mood disorders, autism spectrum disorder, ADHD, psychosis, sleep disorders, and substance-related conditions. Twenty-four studies (n = 2,855; 1,503 patients, 1,352 controls) reporting bilateral DTI-ALPS measures were included in the meta-analysis. The pooled random-effects model revealed a significant transdiagnostic reduction in DTI-ALPS index in psychiatric populations compared with healthy controls (Hedges' g = -0.78, 95% CI -1.01 to -0.55, p < 0.0001). Between-study heterogeneity was substantial (I² = 86.3%), and there was evidence of small-study effects.
Conclusions
Bilateral DTI-ALPS index showed a robust but heterogeneous reduction across psychiatric disorders. These results suggest that impairments of perivascular diffusion, as indexed by DTI-ALPS, may reflect a shared transdiagnostic pattern across psychiatric conditions. Harmonised imaging pipelines and multimodal validation are needed to clarify the biological and clinical significance of these findings.