Analyzing the genes related to nicotine addiction or schizophrenia via a pathway and network based approach

Ying Hu, Zhonghai Fang, Yichen Yang, Dekai Rohlsen-Neal, Feng Cheng, Ju Wang
2018 Scientific Reports  
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
more » ... 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. Schizophrenia is a severe psychiatric disorder with 1% of the life-time prevalence in the general population 1,2 . Patients suffering from schizophrenia may show protean manifestations including auditory hallucinations, weird delusions, significant social withdrawal, difficulty in learning/memory retention, and disorganized speech 3 . Currently, there is still no effective treatment for schizophrenia, and those available largely consist in the using of antipsychotic drugs combined with psychological therapies and other approaches. Thus, developing better approaches for schizophrenia treatment remains a pressing task for public health 1 . Epidemiological studies have shown that individuals with schizophrenia have a higher incidence of substance use as compared to the general population 4-7 . Especially, there is a high prevalence of tobacco smoking among those suffering from the disorder. It has been found that more than 80% of individuals with schizophrenia smoke and are nicotine dependent, compared to the smoking rate of about 25% in the normal individuals 8 . Also, patients suffering from the disorder often smoke high-tar cigarettes and extract more nicotine per cigarette than the common smokers 9 . Moreover, compared to smokers without mental illness, people with schizophrenia face additional challenges, making it more difficult for them to quit smoking 10,11 . Thus, 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. One hypothesis is that the use of tobacco in schizophrenic is mainly driven by self-medication since some psychiatric symptoms of schizophrenia can be relieved by smoking [12] [13] [14] . There are two main arguments for this hypothesis, one is Published: xx xx xxxx OPEN www.nature.com/scientificreports/
doi:10.1038/s41598-018-21297-x pmid:29440730 pmcid:PMC5811491 fatcat:gcb6kwvtgrbc3dlmghfhja3pma