UC San Diego

Abstract Background: The purpose of this study was to evaluate the role of tobacco use in the development of psychosis in individuals at clinical high risk. Methods: The North American Prodrome Longitudinal Study is a 2-year multisite prospective case–control study of persons at clinical high risk that aims to better understand predictors and mechanisms for the development of psychosis. The cohort consisted of 764 clinical high risk and 279 healthy comparison subjects. Clinical assessments included tobacco and substance use and several risk factors associated with smoking. Results: Clinical high risk subjects were more likely to smoke cigarettes than unaffected subjects (Light Smoking OR = 3.0, 95%CI = 1.9–5; Heavy Smoking OR = 4.8, 95%CI = 1.7–13.7). In both groups, smoking was associated with substance use, stressful life events, and perceived discrimination and in clinical high risk subjects with childhood emotional neglect and adaption to school. Clinical high risk subjects reported higher rates of several factors previously associated with smoking. After controlling for these factors, the relationship between clinical high risk state and smoking became non-significant (Light Smoking OR = 1.9, 95%CI = 0.7–5.2; Heavy Smoking OR = 0.9, 95%CI = 0.1–7.2). Moreover, baseline smoking status (HR = 1.16, 95%CI = 0.82–1.65) and categorization as ever smoked (HR = 1.3, 95%CI = 0.8–2.1) did not predict time to conversion. Conclusion: Persons at high risk for psychosis are more likely to smoke compared to unaffected persons. Factors associated with smoking in both groups were more common in the clinical high risk cohort, and smoking status in clinical high risk subjects did not predict conversion risk. These findings did not support a causal relationship between smoking and psychosis. Funding: This study was supported by the National Institute of Mental Health (NIMH) [grant U01 MH081984 to J.A.; grants U01 MH081928; P50 MH080272; Commonwealth of Massachusetts SCDMH82101008006 to L.J.S.; grants R01 MH60720, U01 MH082022 and K24 MH76191 to K.S.C.; grant U01 MH081902 to T.D.C.; P50 MH066286 (Prodromal Core) to C.E.B.; grant U01 MH082004 to D.O.P.; grant U01 MH081988 to E.F.W.; grant U01 MH082022 to S.W.W.; and U01 MH081857-05 grant to B.A.C.] and the National Institute of Environmental Health Sciences (NIEHS) grant T32ES007018 to M.T.W. The NIMH and NIEHS had no further role in study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication.