Researchers in Canada, using an advanced brain imaging method, say they may be able to explain why smokers are at high risk for clinical depression. Senior scientist Dr. Jeffrey Meyer and colleagues at the Centre for Addiction and Mental Health discovered that MAO-A levels in the brain regions that control mood rose by 25 percent 8 hours after withdrawal from heavy cigarette smoking. MAO-A "eats up" chemicals in the brain, such as serotonin, that help maintain a normal mood. When MAO-A levels are higher, as in early cigarette withdrawal, it means this removal process is overly active, making people feel sad. For this study, MAO-A was detected using a brain imaging technique called positron emission tomography. These levels were much higher than in a comparison group of non-smoking study participants. All 48 study participants filled out questionnaires and smokers with high brain MAO-A levels during withdrawal also reported greater feelings of sadness, the researchers say. "Understanding sadness during cigarette withdrawal is important because this sad mood makes it hard for people to quit, especially in the first few days. Also, heavy cigarette smoking is strongly associated with clinical depression," Meyer says in a statement. The study, published in the Archives of General Psychiatry, says a specific substance in cigarette smoke -- harman -- may be responsible for these changes.