Aberrant expression of BDNF might serve as a candidate target for cocaine-induced psychosis: insights from
Youwei Zhu1, Yan Zhao1, Xiaomin Xu1
1Shanghai Drug Abuse Treatment Center, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Background:
Cocaine use disorder (CUD) and associated psychosis are major public health issues worldwide, along with high relapse outcome and limited treatment options. Exploring the molecular mechanisms underlying cocaine-induced psychosis (CIP) could supply integrated insights for understanding the pathogenic mechanism and potential novel therapeutic targets.
Aims:
The aim of the study was to explore common alterations of CUD-schizophrenia-target genes and identify core risk genes contributing to CIP through data mining and network pharmacology approach.
Methods:
Target genes of CUD were obtained from GeneCards, Comparative Toxicogenomics Database, Swiss Target Prediction platform and PubChem. Schizophrenia-related target genes were derived from DisGeNET, GeneCards, MalaCards and Online Mendelian Inheritance in Man databases. Then, the overlap genes of these two sets were regarded as risk genes contributing to CIP. Based on these CUD-schizophrenia-target genes, functional annotation and pathway analysis were performed using the clusterProfiler package in R. Protein-protein interaction network construction and module detection were performed based on the Search Tool for the Retrieval of Interacting Genes (STRING) database and Cytoscape software. Gene expression datasets GSE54839 and GSE93577 were applied for data validation and diagnostic capacity evaluation of interested hub genes.
Results:
A total of 165 CUD-schizophrenia-target genes were obtained. These genes were mainly contributing to chemical synaptic transmission, neuropeptide hormone activity, postsynaptic membrane and neuroactive ligand-receptor interaction pathway. Network analysis and validation analysis indicated that BDNF might serve as an important risk gene in mediating CIP.
Conclusions:
This study generates a holistic view of CIP and provides a basis for the identification of potential CUD-schizophrenia-target genes involved in the development of CIP. The abnormal expression of BDNF would be a candidate therapeutic target underlying the pathogenesis of CUD and associated CIP.
Insights
Cocaine use disorder (CUD) and associated psychosis (CIP) impact public health. This study identified 165 CUD-schizophrenia genes, highlighting BDNF as a key risk gene for CIP, offering potential therapeutic targets.
Area of Science:
- Neuroscience
- Genetics
- Pharmacology
Background:
- Cocaine use disorder (CUD) and associated psychosis (CIP) present significant global health challenges with limited treatment options.
- Understanding the molecular underpinnings of CIP is crucial for developing effective interventions and novel therapeutic targets.
Purpose of the Study:
- To identify common genetic alterations between CUD and schizophrenia.
- To pinpoint core risk genes contributing to CIP using a data mining and network pharmacology approach.
Main Methods:
- Integrated gene data from multiple databases for CUD and schizophrenia.
- Performed functional annotation, pathway analysis, and protein-protein interaction network construction.
- Validated key genes using gene expression datasets (GSE54839, GSE93577).
Main Results:
- Identified 165 overlapping CUD-schizophrenia target genes.
- These genes are primarily involved in synaptic transmission and neuroactive ligand-receptor interactions.
- BDNF was identified as a significant risk gene mediating CIP.
Conclusions:
- This research provides a comprehensive overview of CIP-related genes.
- Abnormal BDNF expression is a potential therapeutic target for CUD and associated psychosis.
