Monoamine Oxidase A Binding in the Prefrontal and Anterior Cingulate Cortices During Acute Withdrawal From Heavy Cigarette Smoking

Context: 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. Objectives: 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. Design: Study via positron emission tomography of healthy control and cigarette-smoking individuals. Patients: 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). Setting: Tertiary care psychiatric hospital. Main Outcome Measure: An index of MAO-A density, MAO-A V-T, was measured in the prefrontal and anterior cingulate cortices. Results: 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,F-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,F-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,F-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,F-10=11.91, P=.006). Conclusions: 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 long-standing 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.