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Integrative Bioinformatics Analysis Reveals Pathogenesis Biomarkers for Clozapine-Induced Metabolic Syndrome
Yingyi Wang1,2, Haisu Wu3, Ruijie Geng3,4
1Department of Nutritional and Metabolic Psychiatry, The Affiliated Brain Hospital, Guangzhou Medical University, 510370 Guangzhou, Guangdong, China.
Alpha Psychiatry
|January 12, 2026
Summary
Clozapine treatment for schizophrenia can cause metabolic syndrome (MetS). This study identified key genes, including BDNF, linked to MetS development, offering insights for managing this side effect.
Area of Science:
- Genetics and Molecular Biology
- Psychiatry
- Metabolic Disorders
Background:
- Clozapine is an effective antipsychotic for schizophrenia but is associated with metabolic syndrome (MetS).
- The molecular mechanisms driving clozapine-induced MetS remain unclear, hindering effective prevention and management strategies.
- Understanding these mechanisms is crucial for optimizing schizophrenia treatment and patient outcomes.
Purpose of the Study:
- To elucidate the molecular underpinnings of clozapine-induced MetS in schizophrenia patients.
- To identify key genes and pathways involved in the development of MetS during clozapine therapy.
- To provide evidence-based insights for clinicians to manage and prevent MetS in psychiatric patients.
Main Methods:
- Recruited schizophrenia patients with MetS and matched controls.
- Performed peripheral blood RNA sequencing to identify differentially expressed genes (DEGs).
- Utilized Weighted Gene Co-expression Network Analysis (WGCNA), Protein-Protein Interaction (PPI) networks, and Mendelian Randomization (MR) to identify hub genes and validate causal relationships.
Main Results:
- Identified 1019 DEGs, with key hub genes including BDNF, MMP8, ACPL2, and TRAV12-2.
- WGCNA revealed eight mRNA modules, and PPI analysis highlighted BDNF and MMP8.
- MR analysis confirmed a causal link between serum BDNF levels and MetS risk, with enriched pathways including biological oxidation and immune response.
Conclusions:
- Significant gene expression differences exist between schizophrenia patients with and without MetS.
- Individual variations in clozapine-induced MetS may be associated with specific DEGs.
- BDNF emerges as a critical factor in the metabolic dysregulation associated with clozapine treatment.
