Chronic nicotine exposure has direct downstream effects on dopaminergic and glutamatergic neurotransmitter systems with roles in impulsivity and decision-making (Durazzo et al. 2016) that are implicated in the etiology of suicide (Kirch et al. 1987; Oquendo et al. 2014) and which could have both independent effects and additive effects with other static and acute suicide risk factors, consistent with these data. Impulsivity increases with nicotine exposure, normalizes with abstinence, and recurs with re-challenge after abstinence (Kayir et al. 2014; Kolokotroni et al. 2014). In psychiatric samples, smokers have greater impulsivity, aggression, suicidal ideation and suicide attempts and, among those with depression, lower indices of serotonin function (Malone et al. 2003). Nicotine exposure moderates the effect of dopamine receptor gene polymorphisms on major depressive disorder incidence (Korhonen et al. 2014). Additionally, tobacco smoke contains multiple other compounds which may contribute, whose effect on central nervous system function in humans is poorly known (US Department of Health and Human Services, 2014). Finally, hypoxia has been postulated as the underlying mechanism for the association between both living at high altitude and suicide (Kim et al. 2011) and smoking and suicide (Aubin et al. 2011).
