Abstract
OBJECTIVE: The relationship between tobacco smoke exposure (TSE) and depression is controversial. This study combined observational research and Mendelian randomization (MR) to explore the relationship of depression with both smoking status and cotinine levels. METHOD: We collected relevant data from the National Health and Nutrition Examination Survey (NHANES) database from 2005 to 2018, and used weighted multifactorial logistic regression modelling to assess the correlation between TSE and depression, and assessed the causal relationship of depression with both smoking status and cotinine levels by MR. RESULT: Current smokers had the highest risk of depression (OR 1.94; P < 0.01); there was a positive trend for correlation between daily smoking and depression (OR 1.66; P for trend < 0.01). Serum ketamine levels above 3.00 ng/ml had a higher risk of depression (OR 2.13; P < 0.001). MR results showed that current smoking (OR = 4.66; P < 0.001) and previous smoking (OR 2.09; P < 0.01) were risk factors for the onset of depression, and that there was no causal association between cotinine levels and depression. CONCLUSION: Smoking is significantly associated with depression and plays a potential causal role in the development of depression. Cotinine was significantly associated with depression, however MR results showed no causal relationship between cotinine and depression.