MicroRNAs as biomarkers and molecular mediators of cognitive dysfunction in schizophrenia

Abstract

Schizophrenia is a chronic psychiatric disorder characterized by positive, negative, and cognitive symptoms that impair daily functioning. Among these, cognitive dysfunction, affecting memory, attention, and executive function, is a core feature that lacks effective treatment. The clinical diagnosis of schizophrenia is contingent upon the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), which is based on symptom assessment. However, DSM-5 criteria are subjective and lack biological specificity, leading to diagnostic delays and heterogeneity in patient classification. Emerging evidence implies that microRNAs (miRNAs), small non-coding RNAs that regulate gene expression post-transcriptionally, are integral to the molecular pathways contributing to cognitive dysfunction in schizophrenia. Dysregulated miRNAs impact neurodevelopment, synaptic plasticity, and neurotransmitter signaling, key processes implicated in cognitive impairment. Notably, miRNAs can be found in peripheral biofluids, making them promising non-invasive biomarkers for schizophrenia. Their potential diagnostic utility could enhance early detection and classification, overcoming the limitations of symptom-based clinical assessment. This review discusses the function of dysregulated miRNAs in schizophrenia-associated cognitive deficits, their molecular mechanisms, and their implications as biomarkers. Understanding miRNA-mediated regulation of cognitive function could open the door for innovative diagnostic tools and personalized interventions, ultimately improving patient outcomes.

Keywords: Biomarkers; Clinical diagnosis; Cognitive dysfunction; MiRNA; Schizophrenia; Synaptic plasticity.