Yun et al. BMC Public Health 2012, 12:724 http://www.biomedcentral.com/1471-2458/12/724 Page 5 of 7 Table 5 Odds ratio for depression according to duration of smoking cessation among former smokers in men Men Unadjusted Multivariate-adjusted* Duration of smoking cessation < 5 years (n = 636) 5-9 years (n = 436) 10-19 years (n = 640) ≧ 20 years (n = 760) 1.00 (Reference) 1.00 (Reference) 0.92 (0.52-1.64) 0.71 (0.37-1.34) 1.48 (0.74-2.94) 1.32 (0.60-2.88) 1.83 (0.96-3.50) 0.92 (0.39-2.14) Data are presented as mean (standard error) or odds ratio (95% confidence interval). *Adjusted for age, income status, education status, marital status, job status, drinking status, pack-years, BMI, physical activity, Hypertension, Diabetes mellitus, and Cerebrovascular disease. The CES-D is an adequate screening instrument for depressive disorder in the population [25-28]. We used a CES-D cutoff score of 21 as the definition of depression. Although the CES-D has low sensitivity and specificity for minor depression, it is excellent for use as a screen- ing instrument for major depression, and the optimum cutoff point for the CES-D was found to be 21 [25]. Cho et al. also reported that a CES-D score of 21 most effect- ively detected a range of depressive symptoms during screening. They suggested that the higher cutoff point in Korea than in Western countries might be due to differ- ences in the expression of affect, especially the suppres- sion of positive affect, in cultures based on Confucian ethics [20]. Previous reports have proposed mechanisms for the association of smoking with depression. One pharmaco- logical explanation for the influence of smoking on de- pression is that a reduction in monoamine oxidase B (MAO B) activity might synergize with nicotine to pro- duce the diverse behavioral and epidemiological effects of smoking. The brains of smokers showed a 40% de- crease in MAO B level relative to nonsmokers or former-smokers [29]. Another explanation is that vulner- ability to depression is related to certain factors. Nico- tine is known to affect the neurotransmitters involved in major depression [30]. Nicotine use might increase vul- nerability to depression [31], and dysregulation of the dopaminergic system in an addictive state is a plausible mechanistic pathway to depressive vulnerability [32]. A further explanation is that smoking generates free radi- cals, causing lipid peroxidation, oxidation of proteins, and other tissue damage in smokers [33]. Depression has been associated with elevated reactive oxidative species such as anti-oxidative enzyme activities and lipid peroxi- dation [34]. Our data suggest that associations between smoking status and depression were more likely in females. Some studies reported a strong relationship between smoking and depression in females, rather than in males. Others reported a gender-specific effect, and that females showed a much greater smoking-depression relationship than males in both adolescents [14,35] and adults [15,16]. However, some studies have reported conflicting results. Nakata et al. reported that gender did not modify the effects of smoking on depression [36], and in some studies, an increased risk of depression was observed in male, but not female, smokers [37-39]. One possible ex- planation for this gender difference is that female smo- kers may have a lower threshold for depression than male smokers. McKee et al. reported that stressful life events were more strongly related to smoking in females than in males [40]. However, gender-specific effects in the smoking–depression relationship remain incom- pletely understood. In this study, current-smokers had a higher risk of de- pression than never-smokers among both males and females. Although no statistically significant association was seen in males, former-smokers had a lower risk of depression than current-smokers. Wisebeck et al. reported that former-smokers carried a risk of depres- sion that was significantly lower than that of current- smokers, but higher than in never-smokers [41]. They suggested that their results are in accordance with the hypothesis that smoking cessation was an effective way to reduce the risk of depression, and if so, depression should be less frequent in former-smokers who stopped smoking a long time ago compared to those who stopped recently [41]. However, in their study, the differ- ence between the association of distant (first 3 years) smoking cessation and recent (within 1 year) smoking cessation with depression was not significant [41]. Mykletun et al. also reported no associations between depression and time since cessation in former-smokers [38]. They explained that although a trend toward a lower prevalence of depression with time since cessation was detected, it was not statistically significant [38]. Our results are similar; the risk of depression did not signifi- cantly decrease with increasing duration of smoking ces- sation in both males and females. We also evaluated the relationship between the age of starting smoking and de- pression, and no significant increased risk of depression was observed according to decreasing age of starting smoking. Some studies have reported that smoking dur- ing adolescence predicted depression later in life com- pared with never-smokers [14,42,43]. However, to our knowledge, no study had evaluated the relationship