Risk for incident schizophrenia is doubled in patients who actively smoke tobacco, while prenatal exposure to cigarette smoke is associated with a higher risk of offspring developing schizophrenia later in life, according to a study published in Nicotine & Tobacco Research.

This systematic review and meta-analysis sought to explore the effect of tobacco smoking and prenatal smoke exposure on the risk for incident schizophrenia.

Researchers searched international databases, including Medline, EMBASE, PsychInfo, Maternity and Infant Care, and Web of Science, and identified 12 comparative observational studies relating the risk for schizophrenia to smoking status. Two investigators independently extracted relevant data and scored the articles for quality. Outcome measures were drawn from odds ratios and hazard ratios with 95% confidence intervals and were pooled together to estimate relative risks. These estimates were further used in a meta-analysis assuming constant risk over time.

Of the 12 eligible studies, 9 were cohort and 3 were case-control studies. Five articles were concerned with active tobacco smoking, while 7 were focused on prenatal tobacco smoke exposure. The overall quality of the studies used in the systematic review was good, with a median score of 7.5.

A pooled analysis of active smoking studies showed that tobacco smoking was significantly associated with an increased risk for schizophrenia vs never smoking; the combined effect demonstrated a relative risk of 1.99 (95% CI, 1.10-3.61; I²=97%, 5 studies). For the studies relating to prenatal exposure, a pooled analysis found that offspring who were exposed to maternal cigarette smoke as fetuses had an increased risk of developing schizophrenia by 29% (95% CI, 1.10-1.51; I²=71%, 7 studies). Sensitivity analyses determined there was no significant difference between the results from studies reporting outcome measures as odds ratios or hazard ratios.

A limitation of the meta-analysis was the pooling of odds ratios and hazard ratios, in which the odds ratios slightly overestimated the true relative risk. Potential confounding factors, such as ethnicity, substance abuse, cannabis use, or maternal adverse life events, were not adjusted for, potentially limiting the review. A final limitation was the observational nature of the studies, which prevented the ability of the authors to infer causation.

The relationship between active smokers and schizophrenia may be explained by patients who smoke to relieve psychotic symptoms. However, the prevalence of patients with schizophrenia who smoked prior to disease onset—as well as the likelihood of schizophrenia developing in offspring exposed to prenatal smoke—suggests that smoking may be an independent risk factor for schizophrenia. Further studies are needed to investigate the possibility of a causal link between smoking and schizophrenia.

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This study was supported by the Medical Research Council, the UK Centre for Tobacco and Alcohol Studies, the British Heart Foundation, Cancer Research UK, the Economic and Social Research Council, and the National Institute of Health Research.


Hunter A, Murray R, Asher L, Leonardi-Bee J. The effects of tobacco smoking, and prenatal tobacco smoke exposure, on risk of schizophrenia: a systematic review and meta-analysis [published online August 9, 2018]. Nicotine Tob Res. doi: 10.1093/ntr/nty160/5068276