Examining the effect of smoking on suicidal ideation and attempts: Triangulation of epidemiological approaches

Background: Previous literature has demonstrated a strong association between cigarette smoking, suicidal ideation and suicide attempts. This association has not previously been examined in a causal inference framework and could have important implications for suicide prevention strategies. 

Aims: We aimed to examine the evidence for an association between smoking behaviours (initiation, smoking status, heaviness, lifetime smoking) and suicidal thoughts or attempts by triangulating across observational and Mendelian randomisation analyses. 

Method: First, in the UK Biobank, we calculated observed associations between smoking behaviours and suicidal thoughts or attempts. Second, we used Mendelian randomisation to explore the relationship between smoking and suicide attempts and ideation, using genetic variants as instruments to reduce bias from residual confounding and reverse causation. 

Results: Our observational analysis showed a relationship between smoking behaviour, suicidal ideation and attempts, particularly between smoking initiation and suicide attempts (odds ratio, 2.07; 95% CI 1.91-2.26; P < 0.001). The Mendelian randomisation analysis and single-nucleotide polymorphism analysis, however, did not support this (odds ratio for lifetime smoking on suicidal ideation, 0.050; 95% CI -0.027 to 0.127; odds ratio on suicide attempts, 0.053; 95% CI, -0.003 to 0.110). Despite past literature showing a positive dose-response relationship, our results showed no clear evidence for a causal effect of smoking on suicidal ideation or attempts. 

Conclusions: This was the first Mendelian randomisation study to explore the effect of smoking on suicidal ideation and attempts. Our results suggest that, despite observed associations, there is no clear evidence for a causal effect.