Bacher Ingrid, Houle Sylvain, Xu Xin, Zawertailo Laurie, Soliman Alexandra, Wilson Alan A, Selby Peter, George Tony P, Sacher Julia, Miler Laura, Kish Stephen J, Rusjan Pablo, Meyer Jeffrey H
Vivian M. Rakoff PET Imaging Centre, Centre for Addiction and Mental Health, University of Toronto, 250 College St., Toronto, ON, Canada.
Arch Gen Psychiatry. 2011 Aug;68(8):817-26. doi: 10.1001/archgenpsychiatry.2011.82.
Greater prefrontal cortex and anterior cingulate cortex monoamine oxidase A (MAO-A) binding is associated with depressed mood. Substances in cigarette smoke, such as harman, inhibit MAO-A, and cigarette withdrawal is associated with depressed mood. Dysphoria during cigarette withdrawal predicts relapse. It is unknown whether MAO-A binding increases during early cigarette withdrawal.
To measure prefrontal and anterior cingulate cortex MAO-A binding during acute cigarette withdrawal and to assess the relationship with smoking severity, plasma levels of harman, and severity of depression.
Study via positron emission tomography of healthy control and cigarette-smoking individuals.
Twenty-four healthy nonsmoking and 24 otherwise healthy cigarette-smoking individuals underwent positron emission tomography with harmine labeled with carbon 11. Healthy nonsmoking individuals underwent scanning once. Cigarette-smoking individuals underwent scanning after acute withdrawal and after active cigarette smoking. Cigarette smoking was heavy (≥25 cigarettes per day) or moderate (15-24 cigarettes per day).
Tertiary care psychiatric hospital.
An index of MAO-A density, MAO-A V(T), was measured in the prefrontal and anterior cingulate cortices.
In heavy-smoking individuals, prefrontal and anterior cingulate cortex MAO-A V(T) was greater during withdrawal (23.7% and 33.3%, respectively; repeated-measures multivariate analysis of variance, F(1,22) = 25.58, P < .001). During withdrawal from heavy smoking, prefrontal and anterior cingulate cortex MAO-A V(T) was greater than in healthy controls (25.0% and 25.6%, respectively; multivariate analysis of variance, F(2,33) = 6.72, P = .004). The difference in MAO-A V(T) in the prefrontal cortex and anterior cingulate cortex between withdrawal and active, heavy smoking covaried with change in plasma harman levels in the prefrontal cortex and anterior cingulate cortex (multivariate analysis of covariance, F(1,10) = 9.97, P = .01). The change in MAO-A V(T) between withdrawal and active, heavy smoking also covaried with severity of depression (multivariate analysis of covariance, F(1,10) = 11.91, P = .006).
The increase in prefrontal and anterior cingulate cortex MAO-A binding and associated reduction in plasma harman level represent a novel, additional explanation for depressed mood during withdrawal from heavy cigarette smoking. This finding resolves a longstanding paradox regarding the association of cigarette smoking with depression and suicide and argues for additional clinical trials on the effects of MAO-A inhibitors on quitting heavy cigarette smoking.
前额叶皮质和前扣带回皮质单胺氧化酶A（MAO-A）结合与抑郁情绪相关。香烟烟雾中的物质，如哈尔满，可抑制MAO-A，且戒烟与抑郁情绪有关。戒烟期间的烦躁不安可预测复吸。目前尚不清楚在早期戒烟过程中MAO-A结合是否增加。
测量急性戒烟期间前额叶和前扣带回皮质MAO-A结合情况，并评估其与吸烟严重程度、血浆哈尔满水平及抑郁严重程度的关系。
对健康对照者和吸烟者进行正电子发射断层扫描研究。
24名健康非吸烟者和24名其他方面健康的吸烟者接受了用碳11标记的harmine的正电子发射断层扫描。健康非吸烟者扫描一次。吸烟者在急性戒烟后和主动吸烟后进行扫描。吸烟量为重度（≥25支/天）或中度（15 - 24支/天）。
三级护理精神病医院。
在前额叶和前扣带回皮质测量MAO-A密度指数MAO-A V(T)。
在重度吸烟者中，戒烟期间前额叶和前扣带回皮质MAO-A V(T)更高（分别为23.7%和33.3%；重复测量多变量方差分析，F(1,22) = 25.58，P <.001）。在重度吸烟戒断期间，前额叶和前扣带回皮质MAO-A V(T)高于健康对照者（分别为25.0%和25.6%；多变量方差分析，F(2,33) = 6.72，P =.004）。前额叶皮质和前扣带回皮质在戒烟与主动重度吸烟之间MAO-A V(T)的差异与前额叶皮质和前扣带回皮质血浆哈尔满水平的变化相关（多变量协方差分析，F(1,10) = 9.97，P =.01）。戒烟与主动重度吸烟之间MAO-A V(T)的变化也与抑郁严重程度相关（多变量协方差分析，F(1,10) = 11.91，P =.006）。
前额叶和前扣带回皮质MAO-A结合增加以及血浆哈尔满水平相应降低，为重度吸烟戒断期间的抑郁情绪提供了一种新的额外解释。这一发现解决了长期以来关于吸烟与抑郁和自杀关联的矛盾，并支持就MAO-A抑制剂对重度吸烟戒烟效果进行更多临床试验。
