Brain monoamine oxidase A inhibition in cigarette smokers

Several studies have documented a strong association between smoking and depression. Because cigarette smoke has been reported to inhibit monoamine oxidase (MAO) A in vitro and in animals and because MAO A inhibitors are effective antidepressants, we tested the hypothesis that MAO A would be reduced in the brain of cigarette smokers. We compared brain MAO A in 15 nonsmokers and 16 current smokers with [(11)C]clorgyline and positron emission tomography (PET). Four of the nonsmokers were also treated with the antidepressant MAO inhibitor drug, tranylcypromine (10 mg/day for 3 days) after the baseline PET scan and then rescanned to assess the sensitivity of [(11)C]clorgyline binding to MAO inhibition. MAO A levels were quantified by using the model term λk(3)which is a function of brain MAO A concentration. Smokers had significantly lower brain MAO A than nonsmokers in all brain regions examined (average reduction, 28%). The mean λk(3) values for the whole brain were 0.18 ± 0.04 and 0.13 ± 0.03 cc(brain) (ml(plasma))(−1) min(−1) for nonsmokers and smokers, respectively; P < 0.0003). Tranylcypromine treatment reduced λk(3) by an average of 58% for the different brain regions. Our results show that tobacco smoke exposure is associated with a marked reduction in brain MAO A, and this reduction is about half of that produced by a brief treatment with tranylcypromine. This suggests that MAO A inhibition needs to be considered as a potential contributing variable in the high rate of smoking in depression and in the development of more effective strategies for smoking cessation.

多项研究已证实吸烟与抑郁症之间存在显著关联。鉴于有报道称香烟烟雾可在体外及动物体内抑制单胺氧化酶（MAO）A，且MAO A抑制剂是一类有效的抗抑郁药物，本研究验证了“吸烟者大脑中的MAO A水平会降低”这一假说。我们采用[¹¹C]氯吉兰（[(11)C]clorgyline）与正电子发射断层扫描（positron emission tomography，PET）技术，对比了15名非吸烟者与16名当前吸烟者的大脑MAO A水平。其中4名非吸烟者在基线PET扫描后，接受了抗抑郁MAO抑制剂反苯环丙胺（tranylcypromine，10mg/天，连续3天）治疗，随后再次进行扫描，以评估[¹¹C]氯吉兰结合对MAO抑制的敏感性。MAO A水平以模型参数λk(3)进行量化，该参数是大脑MAO A浓度的函数。结果显示，在所有检测的脑区中，吸烟者的大脑MAO A水平均显著低于非吸烟者，平均降幅达28%。非吸烟者与吸烟者的全脑平均λk(3)值分别为0.18 ± 0.04 cc(脑)(ml(血浆))⁻¹·min⁻¹与0.13 ± 0.03 cc(脑)(ml(血浆))⁻¹·min⁻¹（P < 0.0003）。反苯环丙胺治疗可使各脑区的λk(3)值平均降低58%。本研究结果表明，烟草烟雾暴露可显著降低大脑MAO A水平，其降幅约为短期反苯环丙胺治疗所致降幅的一半。这一发现提示，在抑郁症患者的高吸烟率现象中，MAO A抑制作用可能是一个潜在的相关影响因素，同时也可为开发更有效的戒烟策略提供新思路。