Transdiagnostic Reductions in Glymphatic-Related Perivascular Diffusion Across Psychiatric Disorders: A Systematic Review and Meta-analysis

BackgroundImpaired glymphatic clearance, the perivascular system supporting cerebrospinal and interstitial fluid exchange, 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. MethodsFollowing 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. ResultsThirty-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 (I{superscript 2} = 86.3%), and there was evidence of small-study effects. ConclusionsBilateral DTI-ALPS index showed a robust but heterogeneous reduction across psychiatric disorders. Together, these results suggest that impairments of perivascular diffusion, as indexed by DTI-ALPS, may reflect a shared transdiagnostic vulnerability across psychiatric conditions. Harmonised imaging pipelines and multimodal validation are needed to clarify the biological and clinical significance of these findings. SIGNIFICANCE STATEMENTThe search for reliable transdiagnostic biomarkers remains a central challenge in contemporary psychiatry, where heterogeneous symptom profiles often obscure shared biological pathways. The glymphatic system, a glia-dependent network regulating cerebrospinal and interstitial fluid exchange, has recently been proposed as a key mechanism linking vascular, immune, and metabolic pathways to mental illness. Diffusion tensor imaging along the perivascular space (DTI-ALPS) offers a non-invasive proxy for glymphatic function, yet its specificity and clinical relevance remain debated. This systematic review and meta-analysis provide, to our knowledge, the first quantitative synthesis of DTI-ALPS findings across psychiatric disorders, critically evaluating methodological assumptions and evidence for shared pathophysiological mechanisms. By clarifying the strengths and limitations of diffusion-based glymphatic imaging, this work establishes a mechanistic framework for future translational, interventional, and biomarker research in psychiatry.