Psychiatry Investig.  2024 Jun;21(6):618-628. 10.30773/pi.2024.0011.

Establishment of a Mitochondrial Metabolism-Related Diagnostic Model in Schizophrenia Based on LASSO Algorithm

• Liu Y
• Lin H
• Liu M
• Lin L
• Wen Y

• KMID: 2556617
• DOI: http://doi.org/10.30773/pi.2024.0011

Abstract

Objective
Schizophrenia is a common mental disorder, and mitochondrial function represents a potential therapeutic target for psychiatric diseases. The role of mitochondrial metabolism-related genes (MRGs) in the diagnosis of schizophrenia remains unknown. This study aimed to identify candidate genes that may influence the diagnosis and treatment of schizophrenia based on MRGs.
Methods
Three schizophrenia datasets were obtained from the Gene Expression Omnibus database. MRGs were collected from relevant literature. The differentially expressed genes between normal samples and schizophrenia samples were screened using the limma package. Venn analysis was performed to identify differentially expressed MRGs (DEMRGs) in schizophrenia. Based on the STRING database, hub genes in DEMRGs were identified using the MCODE algorithm in Cytoscape. A diagnostic model containing hub genes was constructed using LASSO regression and logistic regression analysis. The relationship between hub genes and drug sensitivity was explored using the DSigDB database. An interaction network between miRNA-transcription factor (TF)-hub genes was created using the Network-Analyst website.
Results
A total of 1,234 MRGs, 172 DEMRGs, and 6 hub genes with good diagnostic performance were identified. Ten potential candidate drugs (rifampicin, fulvestrant, pentadecafluorooctanoic acid, etc.) were selected. Thirty-four miRNAs targeting genes in the diagnostic model (ANGPTL4, CPT2, GLUD1, MED1, and MED20), as well as 137 TFs, were identified.
Conclusion
Six potential candidate genes showed promising diagnostic significance. rifampicin, fulvestrant, and pentadecafluorooctanoic acid were potential drugs for future research in the treatment of schizophrenia. These findings provided valuable evidence for the understanding of schizophrenia pathogenesis, diagnosis, and drug treatment.

Keyword

Schizophrenia; Mitochondrial metabolism; LASSO algorithm; Diagnostic model; miRNA-TF-hub gene network