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MicroRNAs in metabolic effects with atypical antipsychotics-a scoping review
Weng Tong Wu1, Deonna Setiawan2, Stephen J Glatt3
1Discipline of Psychiatry and Mental Health, University of New South Wales Sydney, Sydney, NSW, Australia.
Background:
Metabolic side effects associated with atypical antipsychotics represent a major challenge in the clinical management of schizophrenia, contributing to poor treatment adherence and an increased risk of relapse. MicroRNAs (miRNAs) have emerged as promising diagnostic biomarkers for schizophrenia, with growing evidence indicating that their expression is modulated by antipsychotic treatment. Dysregulated miRNAs may not only reflect underlying disease mechanisms but also actively contribute to therapeutic response and the development of metabolic side effects.
Objectives:
This scoping review critically evaluates the current literature on miRNAs in schizophrenia, focusing on their role in modulating treatment response and antipsychotic-induced metabolic disturbances. Key knowledge gaps are identified to inform future translational research.
Eligibility Criteria:
We included studies involving adults or animal models with psychotic symptoms (with schizophrenia as the primary diagnosis) treated with atypical antipsychotics. Eligible studies reported associations between miRNA expression, metabolic parameters, and clinical outcomes.
Sources Of Evidence:
A rapid review was conducted using PubMed to identify relevant articles published up to December 1, 2025 and 16 articles were included for final review.
Charting Methods:
Data charting was performed by one reviewer using a pre-developed and piloted form. The review was reported according to the Preferred Reporting items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR checklist).
Results:
Atypical antipsychotics, particularly those acting on dopamine and serotonin receptors, were shown to modulate specific dysregulated miRNAs. Several of these miRNAs regulate genes involved in metabolic pathways, such as lipid and glucose metabolism, potentially contributing to the variability in cardiometabolic side effects observed across individuals.
Conclusion:
Emerging evidence suggests that miRNAs may play a dual role in mediating both therapeutic efficacy and metabolic risk in schizophrenia treatment. However, the underlying mechanisms remain incompletely understood. Robust, large-scale studies are urgently needed to validate miRNAs as clinically actionable biomarkers for guiding personalized antipsychotic therapy.
Trial Registration:
A protocol was not prospectively registered, as the aim of this scoping review was exploratory in nature.
Insights
MicroRNAs (miRNAs) influence schizophrenia treatment response and metabolic side effects from atypical antipsychotics. Further research is needed to use miRNAs as biomarkers for personalized therapy.
Area of Science:
- Neuroscience
- Genetics
- Pharmacology
Background:
- Metabolic side effects of atypical antipsychotics complicate schizophrenia management.
- MicroRNAs (miRNAs) are implicated in schizophrenia pathogenesis and treatment response.
- miRNAs may influence therapeutic efficacy and metabolic disturbances.
Purpose of the Study:
- To critically evaluate literature on miRNAs in schizophrenia treatment.
- To focus on miRNA roles in treatment response and metabolic side effects.
- To identify knowledge gaps for future translational research.
Main Methods:
- Scoping review of studies on schizophrenia, atypical antipsychotics, and miRNAs.
- Included adult and animal model studies reporting miRNA expression, metabolic parameters, and clinical outcomes.
- Literature search up to December 1, 2025, identified 16 relevant articles.
Main Results:
- Atypical antipsychotics modulate specific dysregulated miRNAs.
- These miRNAs regulate genes involved in lipid and glucose metabolism.
- This modulation may explain variable cardiometabolic side effects.
Conclusions:
- miRNAs may have a dual role in schizophrenia treatment efficacy and metabolic risk.
- Underlying mechanisms require further investigation.
- Large-scale studies are needed to validate miRNAs as biomarkers for personalized therapy.
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