Reason for Depression When Smokers Quit

Acute withdrawal from heavy smoking may increase levels of monoamine oxidase-A (MAO-A), consistent with observations of smoking quitdepressed mood during smoking cessation, results of a brain-imaging study suggest.

Levels of MAO-A in the prefrontal and anterior cingulate cortices increased by as much as 33% during withdrawal as compared with active smoking. Withdrawal-associated levels of MAO-A exceeded those of nonsmoking healthy controls by 25%.

The variations in MAO-A levels between smoking and withdrawal correlated with plasma levels of harman, a beta-carboline found in cigarette smoke, and also with severity of depression, investigators reported in the August issue of Archives of General Psychiatry.

“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,” Ingrid Bacher, PhD, of the University of Toronto, and coauthors wrote in conclusion.

“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.”

Biological concepts related to smoking cessation have focused in large part on nicotine modulation of dopamine-releasing neurons. As applied to therapeutic interventions, the strategy has led to six-month abstinence rates of as much as 40%, the authors noted in the background information.

Cigarette smoke also affects other potential neural targets for smoking cessation, such as MAO-A. For example, a PET imaging study showed that smoking was associated with global reductions in MAO-A binding in smokers versus a control group of nonsmokers (Proc Natl Acad Sci USA 1996; 93: 14065-14069).

MAO-A binding in the prefrontal and anterior cingulate cortices has been implicated in regulation of affect. Additionally, a theoretical basis exists for MAO-A to influence mood during smoking withdrawal, the authors continued.

Many substances in cigarette smoking have a short half-life, including harman. Conceivably, rapid disappearance of the substances from plasma could lead to rapid elevation in MAO-A binding. Whether acute smoking withdrawal increases MAO-A binding has not been investigated previously.

To examine changes in MAO-A binding during smoking withdrawal, Bacher and colleagues recruited 24 otherwise healthy individuals with a history of moderate (15 to 24 cigarettes daily) or heavy (≥25 cigarettes daily) smoking and 24 healthy, nonsmoking controls.

The smoking group consisted of 12 moderate smokers and 12 heavy smokers.

MAO-A binding in the brain was assessed by means of PET with [11C]harmine. Participants in the control group underwent a single PET imaging study. The smokers underwent one imaging study during active smoking and a second study during acute withdrawal. For the withdrawal study, smokers stopped cigarette use eight hours before PET imaging.

Before PET imaging, investigators obtained plasma samples from participants to assess levels of several MAO-A binding substances, including harman. All participants were screened to rule out Axis I or Axis II disorders. Visual analogue scales were used to assess mood, anxiety, and energy at two-hour intervals beginning eight hours before PET imaging.

The primary finding was a significant increase in MAO-A density during withdrawal in the subgroup of heavy smokers. As compared with the active smoking phase, MAO-A increased by 23.7% in the prefrontal cingulate cortex and by 33.3% in the anterior cingulate cortex (P<0.001). The changes were not observed in moderate smokers during withdrawal.

MAO-A density was significantly higher during the withdrawal phase of the 12 heavy smokers as compared with the control group (P=0.004). The magnitude of the difference was 25.0% in the prefrontal cortex (P=0.001) and 25.6% in the anterior cortex (P=0.001).

Changes in plasma harman levels mirrored the PET-detected changes in MAO-A density (P=0.01). Significant correlations were observed for the prefrontal cingulate cortex (P=0.009) and the anterior cingulate cortex (P=0.02).

The VAS scores among heavy smokers also varied with the increases in MAO-A density, exhibiting a significant shift toward depression (P=0.006). Other VAS scores did not vary with MAO-A density.

By Charles Bankhead
MedPage Today

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