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This page is an AI-assisted Turkish summary of the study presented at the 26th World Congress of Psychiatry. The study belongs to the presenting authors; please refer to the original source when citing it.

EV1258

The impact of sleep and glymphatic function on the neurobiology of major depression: a narrative review

THE INFLUENCE OF SLEEP AND GLYMPHATIC FUNCTION ON THE NEUROBIOLOGY OF MAJOR DEPRESSION: A NARRATIVE REVIEW

Glymphatic system dysfunction is proposed as an integrative link connecting sleep disturbances, neuroinflammation, oxidative stress, and HPA axis dysregulation in major depressive disorder.

The aim of this study is to examine the interplay between the glymphatic system (GS), sleep, and the neurobiology of major depressive disorder (MDD). A narrative review was conducted, organized under the headings of conceptual foundations, neurobiology, the role of sleep in glymphatic function, and evidence of glymphatic alterations in depression. MDD affects approximately 5.2% of adults worldwide; according to the DSM-5, diagnosis requires at least five symptoms over a two-week period, including depressed mood or anhedonia. Its pathogenesis involves monoaminergic dysfunction, alterations in the hypothalamic–pituitary–adrenal (HPA) axis, neuroinflammation, and cerebral remodeling. Neuroinflammation and oxidative stress contribute to neuronal damage through reactive oxygen species (ROS) and proinflammatory cytokines (TNF-alpha, IL-1 beta, IFN-gamma); cerebral remodeling includes reduced glial density in the prefrontal cortex, hippocampus, and amygdala. Sleep consists of NREM (stages N1 to N3) and REM stages in cycles lasting approximately 90 to 110 minutes. The GS facilitates cerebrospinal fluid (CSF) influx through periarterial spaces, AQP4-mediated exchange via astrocytes, and metabolite clearance through perivenous pathways, with glymphatic flow increasing markedly during NREM sleep. In MDD, chronic neuroinflammation is reported to impair astrocyte function and AQP4 polarization, reducing glymphatic efficiency. Postmortem studies have identified altered AQP4 expression and reactive astrogliosis, while magnetic resonance imaging findings reveal increased free water in white matter and a reduced ALPS index strongly associated with elevated cortisol and insomnia. Astroglial dysfunction, alterations in circadian clock genes, and HPA axis dysregulation are proposed to form a vicious cycle with sleep disturbances. In conclusion, treatment strategies focusing on sleep regulation, stress modulation, and enhancement of glymphatic function are proposed as integrated approaches, while further studies are needed to validate biomarkers and interventions.

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