The Role of Microglial Exosomes in Clozapine Treatment: Effect on Cognition in Schizophrenia

Schizophrenia is a complex neuropsychiatric disorder characterized by a spectrum of symptoms including cognitive impairments and psychotic episodes. Clozapine, an atypical antipsychotic drug, is a widely recognised treatment option for patients with drug-resistant schizophrenia, due to it having the highest efficacy out of all the antipsychotic drugs. Despite its efficacy, clozapine's impact on cognition and brain structure in schizophrenia patients remains a subject of ongoing research and debate, with accumulating evidence indicating negative impacts on cognitive performance and changes in brain volume. Changes in the immune system are linked to variations in cognitive functioning in schizophrenia. Previous research has indicated that microglia, the primary innate immune cells of the brain, have been associated with decreased cognitive performance when dysfunctional. Evidence suggests that brain structure may mediate the observed relationship between microglia and cognition. Microglial exosomes, integral to neuroinflammation and cellular communication, could provide insight into the neurobiological mechanisms underpinning the effects of clozapine treatment. This review focuses on the proposition that alterations in microglial exosome composition, particularly miRNAs, are involved in mediating clozapine's diverse effects on cognition by influencing brain macrostructure. This review aims to highlight new directions for future research that could lead to more effective and targeted therapeutic approaches in the management of schizophrenia.