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Athanasios Gogos,1,* Maria Skokou,2,* Eleni Ferentinou,1 Philippos Gourzis2 1School of Medicine, University of Patras, Rion, Patras, Greece; 2Department of Psychiatry, University Hospital of Patras, Rion, Patras, Greece*These authors contributed equally to this workCorrespondence: Philippos GourzisDepartment of Psychiatry, General University Hospital of Patras, School of Medicine, University of Patras, University Campus, Rio 26504, GreeceTel +30 2610 990559Fax +30 261 099 4534Email pgourzis@upatras.grAbstract: Recent research has fueled a debate concerning the role of nicotine in the emergence of schizophrenia. The three main hypotheses are: (a) the self-medication effect, (b) the causal relationship hypothesis, or (c) the shared diathesis hypothesis. To explore this role, the study of nicotine consumption during the initial prodromal phase of schizophrenia offers important opportunities. In the present work, 10 relevant studies are reviewed, out of 727 retrieved citations, in order to address questions regarding the prevalence of smoking in the prodromal period, the time of smoking initiation, existing patterns of tobacco use in relation with the escalation of prodromal symptoms into first psychotic episode, and potential differences in symptomatology between smokers and nonsmokers. Even though there was considerable heterogeneity among studies, relevant findings are discussed. Prevalence of nicotine use during the prodromal period was reported to be 16.6–46%. Tobacco use was found to be taken up most often before or during the prodromal period of schizophrenia. Even though a protective role of smoking has been reported by one study, other studies report an increased risk for psychosis, with hazard ratios 2.77 (95% CI: 2.34–3.43) and 2.21 (95% CI: 1.11–4.42) for female and male heavy smokers (11–20 and >20 cigarettes/day), respectively. In a different study, the risk of onset was associated with the progressive use of cannabis and tobacco prior to onset, particularly with rapid escalation to the highest levels of use. Also, nicotine use in ultra high risk (UHR) for developing psychosis subjects is associated with elevated cognitive performance, namely better processing speed, visual learning, and spatial working memory. As a conclusion, it appears that evidence accumulates supporting a possible etiologic role of smoking, in the emergence of schizophrenia along with diverse effects on patients’ symptomatology, already demonstrable at the prodromal phase. Future research employing better-defined criteria should further explore the patterns of use and effects of nicotine during the schizophrenia prodrome.Keywords: tobacco, smoking, psychosis, ultra high risk, conversion, clinical high risk