A twin study of depression and nicotine dependence: shared liability or causal relationship?

Background: The nature of the relationship between major depression (MD) and phenotypes related to smoking behavior, including nicotine dependence (ND), is complicated. We present results from analyses comparing models wherein MD and ND are influenced by a shared latent factor to one in which causal pathways between phenotypes are examined.

Method: Data were collected for 2906 adult male twins from a population-based sample. Structural equation modeling was used to derive path estimates for shared liability and causal models. MD was assessed according to DSM-III-R diagnostic criteria; ND was assessed using the Fagerstrom Test for Nicotine Dependence (FTND).

Results: The best fitting shared liability model included genetic, but not environmental, influences shared between MD and FTND; a small proportion of these shared influences were also common to smoking initiation. The best fitting causal model included a unidirectional causal path from FTND to MD, with no direct genetic correlation between MD and smoking initiation. Model fit statistics indicated that these models provided nearly identical fits to the data, with the causal model providing a slightly superior AIC value.

Conclusions: The phenotypic association between MD and FTND is likely due to both a causal relationship, wherein increasing levels of nicotine dependence increase one's risk for depression, and to a shared genetic liability between the two.

Limitations: This sample consists of Caucasian males born in Virginia, and findings might not be generalizable to others. Statistical power was less than ideal.