We have yielded some new findings by including a broader range of psychiatric correlates, using a lifetime diagnosis and specifying subtypes of smokeless tobacco use. Unlike cigarette smoking, which is associated with a broad range of psychiatric disorders, lifetime smokeless tobacco use is associated with a subset of lifetime diagnoses of psychiatric disorders. The profile of lifetime psychiatric correlates is different depending on the type of smokeless tobacco used. For example, panic disorder and specific phobia were associated with a greater likelihood of exclusive chewing tobacco in our study, consistent with a positive association between smokeless tobacco use and specific phobia was reported among people with nicotine dependence previously [10]. A positive association between lifetime cannabis use disorder and lifetime exclusive snuff use was found in this study, inconsistent with the previous study which concluded that smokeless tobacco use was not associated with cannabis use disorder [11]. We demonstrated a strong positive association between inhalant or solvent use disorder and exclusive chewing tobacco, which had not been reported previously. Alcohol use disorder is associated with all types of smokeless tobacco use. Furthermore, compared to dual use of snuff and chewing tobacco, exclusive use of either type of smokeless tobacco product is uniquely associated with different lifetime diagnoses of psychiatric disorders.

The present study is different from the previous studies [10], [11] in several important ways. First, in the previous studies, smokeless tobacco use was treated as an independent variable and psychiatric disorders were dependent variables. In the present study, smokeless tobacco use was treated as a dependent variable and psychiatric disorders were independent variables. This analytical approach facilitates detection of whether each psychiatric disorder is independently associated with smokeless tobacco use. Second, unlike previous studies that combined snuff use and chewing tobacco together and focused on comparisons between smoked and smoked plus smokeless tobacco use, the present study exclusively focused on smokeless tobacco use. As such, we were able to examine the effect of specific types of smokeless tobacco use. Third, to maximize the sample size of smokeless tobacco use, lifetime smokeless tobacco users were included in the analysis. In contrast, Goodwin et al. [10] study included only past-year smokeless tobacco users. Agrawal and Lynskey's [11] study divided smokeless tobacco users into exclusive smokeless tobacco users and smoke plus smokeless tobacco use. As a result, the sample size of smokeless tobacco users is significantly reduced. In the present study, it was recognized that many smokeless tobacco users were also smokers. We controlled the smoking effects by including quantities of cigarettes smoked as a covariate. Finally, the relation of smokeless tobacco use with cannabis use and cannabis use disorder was the central focus in a previous study [11], while the present study examined a broad spectrum of psychiatric disorders in relation to each specific type of smokeless tobacco use.

Exclusive smokeless tobacco use has been linked to alcohol use disorder [11]. Our study extends the previous finding by demonstrating that alcohol use disorder is associated with all types of smokeless tobacco use. Moreover, the association between dual use and alcohol use disorder is much stronger than that between exclusive use of either type of smokeless tobacco and alcohol use disorder. This strong association cannot be explained by cigarette smoking, sociodemographics and other psychiatric disorders. The biological mechanism of the association between smokeless tobacco use and alcohol use disorder is not clear. Little research has elucidated the biological link between smokeless tobacco and alcohol dependence. Alcohol dependence and cigarette smoking are associated with low platelet monoamine oxidase (MAO) activity levels. Cigarette smoking leads to the binding of an inhibitor contained in cigarette smoke to platelet MAO-B at the catalytic site of MAO. However, a recent Swedish study compared the MAO activity of three groups of tobacco use among alcohol dependent subjects: non-tobacco users (n = 46), snuff users (n = 14), and cigarette users (n = 33) [24]. The MAO activity levels were significantly lower in cigarette smokers, but not in snuff users, compared to non-tobacco users. This finding suggests that snuff use may not have an inhibitory effect on MAO activities among alcohol dependence users. It is unknown if this phenomenon can be observed in people without alcohol dependence. Low aldehyde dehydrogenase (ALDH) activity is a marker of alcohol dependence. The mean whole blood ALDH activity of the smokers was found to be reduced significantly in smokers, but not in snuff users [25], even though cigarette smokers and snuff users had similar plasma nicotine and cotinine levels. The investigators speculated that the reduced blood ALDH activity in smokers was not caused by nicotine or any of its metabolites, but more likely, by components formed during the combustion of tobacco. In combination, these studies suggest that the biological mechanism underlying the association between cigarette use and alcohol use disorder cannot be automatically extrapolated to the relationship between smokeless tobacco use and alcohol use disorder. More research is needed to uncover the underlying mechanism.

The present study did not identify a significant relationship between possession of any mood disorder and smokeless tobacco use, consistent with a previous report in the USA[10], but inconsistent with a Finnish adolescent longitudinal study that found that early onset depressive disorders predicted two times the risk for smokeless tobacco use three years later [26]. These inconsistent findings could be attributable to study design (i.e. longitudinal vs. cross-sectional), difference in controlling for confounding effects, and different cultural factors that exist between Finland and USA.

The finding of an association between inhalant/solvent use disorder and exclusive chewing tobacco is quite novel. People who had a lifetime diagnosis of inhalant or solvent use disorder are three times more likely to chew tobacco than those without inhalant/solvent use disorder. Previous studies have shown that inhalant abuse is usually initiated during preadolescence [27] and chewing tobacco often begins in adulthood [28]. Therefore, people with a history of inhalant abuse may be at high risk for chewing tobacco at some point in their life. Our novel finding may inform the primary prevention effort for chewing tobacco use. Future research that uses a prospective design is needed to confirm our hypothesized pathway.

Dual use of snuff and chewing tobacco versus exclusive use of one of the two types of smokeless tobacco has not been investigated previously. The present study found that both panic disorder and specific phobia were associated with greater odds of exclusive chewing tobacco rather than exclusive snuff use and dual use of both smokeless tobacco products. These findings suggest that chewing tobacco is specifically linked to panic disorder and specific phobia. In addition, schizoid and antisocial personality disorder is less likely to be associated with exclusive use of snuff and chewing tobacco, respectively, than dual use. These results may inform secondary prevention of smokeless tobacco use. Depending on different types of smokeless tobacco used, one or two particular psychiatric comorbidities should be taken into account during the treatment.

The present study's results should be interpreted within the context of several limitations. Because present findings were derived from a cross-sectional study, causal relations between smokeless tobacco and psychiatric disorders cannot be determined. Lifetime diagnoses of psychiatric disorders and lifetime smokeless tobacco use used in this study may obscure some true relationships between smokeless tobacco use and psychiatric disorders. It is also possible that the observed associations are due to a common cause that was not measured in this study. Future studies employing prospective design are needed to unravel the mechanism that underlies the identified associations. The present study's findings were derived based on interviews with adults 18 years or older included in the NESARC dataset and the vast majority of smokeless users were men. Thus, results may not apply equally well to the adolescent population. Future research in that special population is needed to confirm current findings. Finally, we could not examine the subtypes of smokeless tobacco use in relation to heroin use disorder due to a small proportion of smokeless tobacco users who met the lifetime DSM-IV diagnostic criteria for heroin use disorder.

Despite those limitations, this is the first epidemiologic study of its kind to systematically examine the associations between each specific type of lifetime smokeless tobacco use and lifetime diagnoses of psychiatric disorders. As such, these findings provide new insights into the link of psychiatric disorders with snuff use and chewing tobacco. These links are understudied yet given the public health significance of smokeless tobacco product and their health consequences. Thus, elucidating the link between psychiatric and behavioral health factors is important. These results can guide treatment efforts on smokeless tobacco by targeting the treatment for alcohol use disorder among all smokeless tobacco users, the treatment for panic disorder, specific phobia, and inhalant use disorder among exclusive chewing tobacco users, as well as the treatment for cannabis use disorder among exclusive snuff users. It is helpful to realize that persons who use both snuff and chewing tobacco are different from exclusive users of snuff or chewing tobacco regarding their comorbid antisocial and schizoid personality disorders, respectively.