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Front Psychiatry. 2018 Nov 20;9:607. doi: 10.3389/fpsyt.2018.00607. eCollection 2018.

Evidence of a Causal Relationship Between Smoking Tobacco and Schizophrenia Spectrum Disorders.

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Faculty of Medicine, The University of Queensland, Herston, QLD, Australia.
Queensland Centre for Mental Health Research, Wacol, QLD, Australia.
Metro North Mental Health, Royal Brisbane and Women's Hospital, Herston, QLD, Australia.
Faculty of Medicine, University of Turku, Turku, Finland.
Department of Psychiatry, South-Western Hospital District, Turku, Finland.
Center for Life Course Health Research, University of Oulu, Oulu, Finland.
Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland.


There has been emerging evidence of an association between tobacco smoking and schizophrenia spectrum disorders (SSD). Two meta-analyses have reported that people who smoke tobacco have an ~2-fold increased risk of incident schizophrenia or psychosis, even after adjusting for confounding factors. This study aimed to critically appraise the research which has examined the association between tobacco smoking and SSD against the Bradford Hill criteria for causality, to determine the strength of the evidence for a causal relationship. Eight longitudinal studies (seven cohort studies and one case control study) were identified which examined tobacco smoking as an exposure and psychosis as an outcome. All seven cohort studies were assessed as being of high quality using the Newcastle-Ottawa Scale. Six of the eight studies found a statistically significant positive association between tobacco smoking and onset of SSD. These studies reported a consistent association with a moderate to large effect size and a dose response relationship. The studies adjusted for multiple potential confounders including age, sex, socioeconomic status, shared genetic risk, prodromal symptoms, and comorbid cannabis and other substance use. The studies did not adjust for exposure to childhood trauma or prenatal tobacco. There was substantial though inconclusive evidence supporting a causal relationship between tobacco smoking and increased risk of SSD. If a causal relationship does exist, nicotine is most likely responsible for this association. This raises serious public health concerns about the increasing use of e-cigarettes and other products, particularly by adolescents whose nicotine use may increase their risk of SSD. Research is urgently needed to examine the association between e-cigarette use and incident psychosis, particularly in adolescents and young adults.


association; causal; e-cigarette; nicotine; psychosis; schizophrenia; smoking

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