Abstract
The prevalence of tobacco use in people with schizophrenia is much higher than in general population, which indicates a close relationship between nicotine addiction and schizophrenia. However, the molecular mechanism underlying the high comorbidity of tobacco smoking and schizophrenia remains largely unclear. In this study, we conducted a pathway and network analysis on the genes potentially associated with nicotine addiction or schizophrenia to reveal the functional feature of these genes and their interactions. Of the 276 genes associated with nicotine addiction and 331 genes associated with schizophrenia, 52 genes were shared. From these genes, 12 significantly enriched pathways associated with both diseases were identified. These pathways included those related to synapse function and signaling transduction, and drug addiction. Further, we constructed a nicotine addiction-specific and schizophrenia-specific sub-network, identifying 11 novel candidate genes potentially associated with the two diseases. Finally, we built a schematic molecular network for nicotine addiction and schizophrenia based on the results of pathway and network analysis, providing a systematic view to understand the relationship between these two disorders. Our results illustrated that the biological processes underlying the comorbidity of nicotine addiction and schizophrenia was complex, and was likely induced by the dysfunction of multiple molecules and pathways.
Highlights
Schizophrenia is a severe psychiatric disorder with 1% of the life-time prevalence in the general population[1,2]
According to the enrichment results exported by DAVID, 160 biological processes (BP) Gene Ontology (GO) terms were significantly enriched in NAgenes and 167 BP GO terms were enriched in SCZgenes (Supplemental Tables S4 and S5)
The phenotype or disease status is rarely a straight-forward dysfunction in a specific gene or pathway, but rather is an interplay between multiple genes that collectively induces the dysfunctional effects on multiple biological pathways and causes the clinic outcome eventually[45,46]. Both nicotine addiction and schizophrenia are complex diseases with numerous genes involved in their aetiology and development; the high prevalence of cigarette smoking in schizophrenia patients implicates a close connection between the two disorders
Summary
Schizophrenia is a severe psychiatric disorder with 1% of the life-time prevalence in the general population[1,2]. Exploring the neurobiological mechanisms that contribute to comorbid nicotine use in schizophrenics is necessary to understand the aetiology and pathogenesis of schizophrenia, and will be helpful for developing more effective therapeutic strategies to prevent and treat the two diseases From another prospective, the prevalence of smoking among patients with schizophrenia implicates that some shared neurobiological processes may be responsible for the co-occurrence of the two disorders. A recent study raised an objection with self-medication hypothesis as the authors found that cigarette smoking is not associated with cognitive functioning in first-episode psychosis[18] Both genetic and environmental factors play roles in the aetiology and development of schizophrenia and nicotine addiction. A recent GWAS analysis demonstrates that there is a significant genetic correlation between schizophrenia and smoking behaviors[33]
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