Biological basis for the co-morbidity between smoking and mood disorders

Abstract

Nicotine dependence is still the major preventable cause of death in the developed world, and has strong comorbity with mood disorders including major depression. Depressed patients are more likely to smoke cigarettes, and quitting can precipitate an episode of depression in some subjects. Interestingly, antidepressants, particularly the atypical antidepressant buproprion, are therapeutics that can help smokers quit. Despite these observations, the underlying biological factors of the relationship between smoking and depression remain unclear. Results from clinical and pre-clinical studies have seemed somewhat paradoxical because heightened cholinergic activity can induce depression while both nicotine and nicotinic antagonists can be antidepressant-like. These observations can be reconciled by considering that high affinity nicotinic receptors in the brain can be desensitized by chronic nicotine use, leading to blunted cholinergic activity. Based on this hypothesis, nicotinic antagonists have recently been tested as treatments for depression in human subjects, particularly as adjunct therapy along with classical antidepressants. These data suggest that the relationship between smoking and depression may be partially explained by the fact that depressed patients smoke in an effort to self-medicate depressive symptoms by desensitizing their nicotinic receptors. This possibility suggests new avenues for treatment of both nicotine dependence and depressive disorders.

Figure 1. Simplified representation of the relationship between genetic factors, depressive symptoms, and smoking behavior

Genetic factors contribute to susceptibility to smoking and depression and twin studies show that some of these genetic factors are shared (Kendler et al., 1993, Mccaffery et al., 2003). Depression leads to an increased susceptibility to smoking. Inversely, smoking behavior improves mood and decreases depressive symptoms probably through nicotinic receptor desensitization. Concomitantly, nicotine withdrawal can precipitate depression-like symptoms. Several classes of antidepressants, particularly the atypical antidepressant bupropion, can decrease smoking and help smokers to quit in addition to their ability to improve mood and decrease depressive symptoms.