Glymphatic system and psychiatric disorders

Need for a new paradigm

Bibliographic Data

ID15519199
AuthorsTommaso Barlattani (University of L'Aquila, corresponding author), Alessandro Cavatassi (University of L'Aquila), Antony Bologna (University of L'Aquila), Valentina Socci (0000-0002-4797-6911, University of L'Aquila), Edoardo Trebbi (0000-0002-6553-5917), Maurizio Malavolta (University of L'Aquila), Alessandro Rossi (0000-0001-8723-7622, University of L'Aquila), Vassilis Martiadis (0000-0002-3344-1000), Carmine Tomasetti (0000-0002-3130-6569), Domenico De Berardis (0000-0003-4415-5058), Giorgio Di Lorenzo (0000-0002-0576-4064, University of Rome Tor Vergata), Francesca Pacitti (0000-0002-1634-5332, University of L'Aquila)
Year2025
Volume16
Pages1642605-1642605
Publication date2025-12-04
Peer ReviewedYes
Open AccessYes
TypeARTICLE
VenueFrontiers in Psychiatry (JOURNAL)
Journal identifiersISSN: 1664-0640 • E-ISSN: 1664-0640
PublisherFrontiers Media (PUBLISHER • CH)
DOI10.3389/fpsyt.2025.1642605
PMID41425825
OpenAlexW4416976899
LanguageEN
Citations received4
References cited3

Psychiatric disorders like depression, bipolar disorder, schizophrenia, and post-traumatic stress Disorder have conventionally theorized on alterations in neurotransmitters, receptor pharmacodynamics, and neural connectivity. However, recent research points to a complementary framework involving the glymphatic system, a specialized glial lymphatic pathway that removes metabolic waste products, particularly during deep sleep, through the coordinated action of cerebrospinal fluid, interstitial fluid, and the aquaporin 4 channels of astrocytes. When the glymphatic network is compromised, neurotoxic proteins, such as beta-amyloid and tau, and inflammatory mediators can accumulate, potentially exacerbating insomnia, inflammation, and circadian disturbances. These same processes often occur in psychiatric disorders, fueling oxidative stress, neuroinflammation, and cognitive decline. New neuroimaging methods, such as diffusion tensor imaging and the analysis Along the Perivascular Space, ALPS, index, allow clinicians and researchers to quantify perivascular flow deficits in vivo . Preliminary evidence suggests that enhancing glymphatic function by improving sleep architecture, supporting astrocyte health, or scheduling drug delivery based on circadian fluctuations may offer clinical benefits. Here, we present an overview of glymphatic biology, examine its relevance to psychiatric pathophysiology, highlight findings from emerging neuroimaging studies, and consider ways modulating glymphatic flow may improve psychiatric pharmacotherapy

Aquaporin 4 · Cerebrospinal fluid · Cognition · Default mode network · Diffusion MRI · Glymphatic system · Neuroimaging · Cerebrospinal fluid and hydrocephalus · Intracerebral and Subarachnoid Hemorrhage Research · Spinal Dysraphism and Malformations

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