6.3 DOES TOBACCO SMOKING CAUSE PSYCHOSIS?

Abstract

Background: Although the association between psychotic illness and cigarette smoking is well known, it is not clear why people with psychosis are more likely to smoke than are the general population. First, we carried out a systematic review and meta-analysis aimed to test the hypothesis that a) daily tobacco use is associated with an increased risk of psychotic illness in both case-control and prospective studies, and b) smoking is associated with an earlier age at onset of psychotic illness. Secondly, we carried out two case-control studies aimed to derive an estimate of the prevalence of smoking in patients presenting with their first episode of psychosis. The first was the GAP study carried out in South London, the second was the EU-GEI multi-site study carried out across 16 sites in Europe and Brazil. Method(s): First, we searched Embase, Medline, and PsycINFO and selected observational studies in which rates of smoking were reported in people with psychotic disorders, compared with controls. We calculated the weighted mean difference for age at onset of psychosis and age at initiation of smoking. For categorical outcomes, we calculated odds ratios from cross-sectional studies and risk ratios from prospective studies. Secondly, in the GAP study, we interviewed 596 people with their first episode of psychosis and 333 healthy controls representative of the local population. In the EU-GEI study, we interviewed 1,150 patients with first episode psychosis and 1,350 healthy controls. In both all subjects were interviewed in detail about their recreational drug use including tobacco use. In the EU-GEI study approximately one half of the cases and controls also underwent an EWAS examination of epigenetics in peripheral blood. Result(s): 61 studies met inclusion criteria for the systematic review, and the overall sample included 14,555 tobacco users and 273,162 non-users. The prevalence of smoking in patients presenting with their first episode of psychosis was 0 57 (95% CI 0 52-0 62; p<0 0001). Daily smokers developed psychotic illness at an earlier age than did non-smokers (weighted mean difference -1 04 years, 95% CI -1 82 to -0 26). In the GAP study, 70.4% of the patients and 47.6% of the controls had ever used tobacco, a significant difference (p < 0.001). In the EU-GEI study, tobacco smoking was again significantly commoner in the patient group, a difference which remained significant after correcting for age, gender and cannabis use. EWAS also showed a significant difference in the tobacco signature between cases and controls thus validating the interview data. Conclusion(s): Daily tobacco use is associated with increased risk of psychosis and an earlier age at onset of psychotic illness. Epigenetics was shown to provide an accurate biological measure of lifetime smoking and may be an alternative to interview. In view of the evidence that administering nicotine to juvenile rats results in a persistent state of hyperactive dopamine activity in the ventral tegmental area (VTA), it seems likely that smoking tobacco is a component cause of psychosis.