Heavy smokers who try to quit are typically affected by unpleasant mood changes. A brain imaging study has showed that certain areas of the brain linked to mood regulation really are affected, providing clues to why some heavy smokers find it so hard to give up. The study, carried out by researchers from the Centre for Addiction and Mental Health, Toronto, was published in the latest issue of Archives of General Psychiatry.

The authors explained that smoking is among the top two preventable causes of death. It is also a key factor for lung disease, cancer, suicide, and coronary artery disease.

The researchers added:

“Although many people who smoke cigarettes would like to quit, the effects of withdrawal frequently lead to relapse. Relapse is particularly problematic in early withdrawal because 50 percent of people relapse within the first 3 days of quitting.”

Prior nicotine-withdrawal research concentrated mainly on nicotine’s modulation of dopamine-releasing neurons.

The authors wrote:

“However, other neural targets that may be important in cigarette withdrawal are affected by cigarette smoke.”

Cigarette smoke has been shown to affect MAO-A (monoamine oxidase A), an enzyme which metabolizes mood-enhancing chemicals. Rising MAO-A levels in the mood-regulating parts of the brain, such as the prefrontal cortex and anterior cingulate cortex have been linked to depressive episodes.

The researchers explained:

“The main hypothesis of this study, is that MAO-A binding increases during acute cigarette withdrawal in regions implicated in affect regulation, such as the prefrontal cortex and the anterior cingulate cortex.”

Ingrid Bacher, Ph.D., and team carried out a study involving 48 participants – 24 of them were not smokers, while the other 24 were smokers but otherwise healthy. Among the smokers, 12 of them smoked from 15 to 24 per day (moderate smokers), while 12 smoked at least 25 cigarettes per day (heavy smokers).

The researchers used PET (positron emission tomography) scans, once on the non-smoking participants and twice on the smoking ones (after having a cigarette, and again after acute withdrawal). All of them had undergone an assessment of their moods, energy levels, anxiety levels, and urge to smoke.

Higher MAO-A density was detected only among the heavy smokers during a cigarette – a rise of 23.7% in the prefrontal cortex, and an increase of 33.3% in the anterior cortex. No elevation was found among the moderate smokers.

In a communiqué, the authors wrote:

“A highly significant interaction between smoking severity and condition (measurement of MAO-A density during active smoking and withdrawal) was noticed among participants who smoked heavily.”

There was a significant difference in MAO-A density levels in the prefrontal and anterior cingulated cortex between the nonsmokers and heavy smokers during nicotine withdrawal. There was also a considerable difference in self-reported mood among the heavy smokers during their smoking and nonsmoking days.

The researchers wrote:

“These results have significant implications for quitting heavy smoking and for understanding what has previously appeared to be a paradoxical association of cigarette smoking with major depressive disorder and suicide. Understanding the neurobiology of heavy cigarette smoking is important because those who smoke heavily are much more likely to have major depressive disorder and to experience medical complications resulting from cigarette smoking.”

Further research, including human trials should be performed using MAO-A inhibiting medications for smokers during their initial period when giving up, the investigators added.

Written by Christian Nordqvist