Extracellular Vesicle-mediated Modulation of Neuroinflammation in Autoimmune Psychosis and Schizophrenia: A Narrative Review
Aigerim Abileva
A
BSTRACT
Background:
Schizophrenia and autoimmune psychosis are heterogeneous conditions in which neuroinflammatory mechanisms, microglial activation, altered synaptic pruning, and blood–brain barrier dysfunction have been implicated. Conventional antipsychotic pharmacotherapy remains essential for symptom control, but it does not directly target putative immune-mediated or regenerative mechanisms that may contribute to illness progression in selected subgroups.
Methods:
A narrative literature search of PubMed, Web of Science, and Scopus was conducted using Boolean queries (last searched March 2026), covering publications from 2015 to 2026. The search focused on extracellular vesicles (EVs), exosomes, neuroinflammation, microglia, synaptic plasticity, schizophrenia, autoimmune psychosis, and related neuroinflammatory models. Nine key sources were selected for narrative synthesis. Because the evidence base was heterogeneous and early-stage, no meta-analysis or formal certainty grading was performed.
Results:
The reviewed literature suggests that EVs, including mesenchymal stromal cell-derived EVs (MSC-EVs), may influence neuroinflammatory and synaptic pathways relevant to psychosis. Direct schizophrenia-related evidence remains limited mainly to preclinical methylazoxymethanol acetate and phencyclidine models, whereas evidence from demyelination, methamphetamine withdrawal, and broader neuropsychiatric models should be interpreted as indirect mechanistic support. Proposed mechanisms include delivery of regulatory microRNAs, modulation of microglial activation, support of neurogenesis and synaptic plasticity, and potential protection of synaptic integrity. No completed schizophrenia-specific clinical trials of MSC-EV therapy were identified.
Conclusions:
MSC-EVs represent an early-stage and hypothesis-generating platform for studying neuroimmune modulation in schizophrenia and autoimmune psychosis. Current evidence is insufficient to support clinical use outside formal trials. Future work should prioritize standardized EV characterization, careful separation of direct psychosis evidence from indirect mechanistic models, and first-in-human safety studies in well-defined neuropsychiatric populations.