| Summary: | Abstract Objective It has been identified that the smoking rate is higher in schizophrenic patients than general population. This study aimed to explore the association between schizophrenia and tobacco use, and provide rational recommendations for clinical care of schizophrenia. Methods We recruited 244 patients with schizophrenia and 225 healthy controls. Of schizophrenia patients, 54 patients were untreated with any antipsychotics over the previous 6 months or first‐episode and drug‐naïve. These patients (nonmedication subgroup) were followed up for 8 weeks. The associations between tobacco use and susceptibility to schizophrenia and psychotic symptoms were analyzed. Results Although there was no significant difference between schizophrenia patients and healthy controls in the entire sample, stratification analysis showed the rate of smoking was higher in male patients versus healthy controls and that male smokers exhibited higher odds ratios for schizophrenia than nonsmokers. Next, when we repeated analyses in first‐episode patients and healthy controls, significant differences were not observed, indicating tobacco use is an outcome rather than a cause of schizophrenia. Furthermore, among nonmedication subgroup, smokers presented with more severe psychotic symptoms at baseline, and better improvement after medication than nonsmokers, suggesting patients with worse symptoms tend to smoke to relieve symptoms. Conclusion This study supports the self‐medication hypothesis. Nonetheless, considering the serious health hazard associated with tobacco use, we should encourage patients to stop smoking. Further investigations are warranted to determine the tobacco constituents that are beneficial or harmful to schizophrenia.
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