Retrospective evidence from a study of osteoporosis in Australian women suggests that smokers are twice as likely to develop major depression.

The study recruited 1,494 women between 1994 and 1997 who were followed up prospectively for a decade. The study authors then interviewed 835 of these women and a further 208 recruited between 2005 and 2007 using the Structured Clinical Interview for DSM-IV-TR.

There were 165 women with a history of major depressive disorder with an onset after the age of 20, of whom 73 were smokers, and 806 controls, of whom 269 were smokers.

A case-control analysis showed that smoking was associated with an age-adjusted odds ratio for major depression of 1.46 (95% CI 1.03-2.07), which was increased to 2.18 (95% CI 1.31-3.65) in women smoking more than 20 cigarettes a day.

A retrospective cohort analysis found that, of the 671 women with no history of major depression at baseline, 13 of 87 smokers and 38 of 584 non-smokers developed major depression during the 10 years of follow-up. There were 87 women smokers at baseline, who were found to be almost twice as likely to develop depression (HR 1.93, 95% CI 1.02-3.69). Adjustment for socio-economic status enhanced the risk (HR 2.01, 95% CI 1.03-3.93), whereas adjustment for alcohol consumption, physical activity and physical illness did not affect the association.

Anhedonia, the inability to experience pleasure, is one of the two core features of depression. The dopaminergic neurones of the mesolimbic system form one of the two main pathways of the brain's 'reward' system, and there is now a large body of evidence to suggest that dopamine signalling is reduced in major depression.¹ The feelings of relaxation and pleasure induced by nicotine are also thought to be mediated by the mesolimbic system.² An association between smoking and depression is therefore plausible.

This study suggests that smoking leads to depression, rather than vice versa, although it is possible that personality traits predispose patients to both depression and smoking.

Smoking may also increase the risk of suicidal behaviour.³ This has been linked to a relationship between smoking, impulsive-aggressive behaviour and impaired serotonin function.⁴

This study suggests that we should encourage our depressed patients to stop smoking once they have achieved remission. However, we need to be aware that, by emphasising the role of lifestyle factors in depression, we may unwittingly make patients feel responsible for their illness, adding to their sense of guilt.