There are three non-exclusive models to explain the comorbidity between nicotine dependence and schizophrenia (Gage and Munafo, 2015a): (1) smoking may lead to the onset of schizophrenia; (2) schizophrenia may cause the development of nicotine dependence (self-medication, for example); and (3) there may be common underlying risk factors, environmental and genetic, that predispose to both schizophrenia and nicotine dependence. Recently, there has been growing evidence to suggest a causal pathway from smoking to schizophrenia. Studies have found that smoking prospectively predicts risk for schizophrenia (Gage et al., 2014; Kendler et al., 2015). Further, the observed association did not arise from smoking onset during the prodromal period of schizophrenia and demonstrated a clear dose-response relationship (Kendler et al., 2015).
