Mineur Yann S, Picciotto Marina R
Yale School of Medicine, Department of Psychiatry, 34 Park Street, 3 Floor Research, New Haven, CT 06508, USA.
J Dual Diagn. 2009;5(2):122-130. doi: 10.1080/15504260902869964.
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.
在发达国家，尼古丁依赖仍是主要的可预防死因，且与包括重度抑郁症在内的情绪障碍有很强的共病性。抑郁症患者更有可能吸烟，而戒烟在某些人身上可能会引发抑郁发作。有趣的是，抗抑郁药，尤其是非典型抗抑郁药安非他酮，是有助于吸烟者戒烟的治疗药物。尽管有这些观察结果，但吸烟与抑郁症之间关系的潜在生物学因素仍不清楚。临床和临床前研究的结果似乎有些矛盾，因为胆碱能活性增强可诱发抑郁症，而尼古丁和烟碱拮抗剂都可能具有类抗抑郁作用。考虑到大脑中的高亲和力烟碱受体可因长期使用尼古丁而脱敏，导致胆碱能活性减弱，这些观察结果可以得到解释。基于这一假设，烟碱拮抗剂最近已在人体中作为抑郁症的治疗方法进行测试，尤其是作为与经典抗抑郁药联合使用的辅助疗法。这些数据表明，吸烟与抑郁症之间的关系可能部分是由于抑郁症患者吸烟是为了通过使烟碱受体脱敏来自我治疗抑郁症状。这种可能性为尼古丁依赖和抑郁症的治疗开辟了新途径。
