MicroRNAs in Neural-Derived Extracellular Vesicles as Biomarkers in First Episode Schizophrenia

Schizophrenia is a significant psychiatric illness characterized by psychosis, social withdrawal, and cognitive difficulties leading to impaired daily functioning. Diagnosis and treatment assessment remain heavily reliant on clinical interviews, which are subjective and lack objective biological indicators. Previous research has established evidence of miRNA dysregulation in schizophrenia through genome-wide association studies, post-mortem brain tissue analysis, and biological fluid studies. A more recent and promising approach involves measuring miRNAs specifically contained within neural-derived extracellular vesicles (NDEs) isolated from plasma. These NDEs carry brain-specific miRNA cargo and can be identified in peripheral blood, offering a less invasive approach compared to cerebrospinal fluid or brain tissue.

This study addresses the identified knowledge gap by investigating plasma NDE miRNAs as novel diagnostic and treatment response biomarkers specifically in first-episode schizophrenia (FES). The focus on FES participants minimizes confounding effects associated with long-term medication use and extended illness duration. The study employs a 12-week mechanistic clinical trial design with clinical assessments, neurocognitive testing (MATRICS), and blood collection for NDE miRNA sequencing at baseline and 12 weeks. MiRNA sequencing will be performed using Illumina NovaSeq6000 following NDE isolation via L1/NCAM antibody immunoprecipitation. Statistical analysis includes differential expression analysis using DESeq, Binary Elastic Net Regression for feature selection, and machine learning models (random forests, gradient boosting, SVM) for predictive performance assessment.