Studying the Molecular Basis for Sex Differences in Depression and Nicotine Addiction

Marina R. Picciotto, Ph.D.,Associate Professor of Psychiatry, Pharmacology and Neurobiology

Depression is more common in women than men, and cigarette smoking is far more prevalent in those with depression (40-60%) compared to the general population. Further, there are distinct differences in smoking behaviors for women versus men, including the fact that it is more difficult for women to quit smoking. The goal of Dr. Picciotto’s research was to begin to understand the relationship between depression and smoking as two inter-related health concerns for women.

Highlighted Study Findings

The interaction of brain chemistry and sex hormones (such as estrogen) likely play an important role in the sex differences seen both in depression and smoking behavior. Dr. Picciotto and her laboratory found that certain molecular structures in the brain implicated in depression are also responsive to the pleasant effects of nicotine, suggesting that smoking may be used to decrease depressive symptoms. Interestingly, female, but not male, mice preferred to drink a nicotine solution rather than water, perhaps indicating that female mice are more sensitive to nicotine. Further, mice who had their ovaries removed no longer preferred nicotine, suggesting that sex-specific hormones such as estrogen, may be important in maintaining smoking behavior. Taken together, these findings suggest that nicotine-responsive molecular structures in the brain affect both smoking behavior and depressive symptoms, and demonstrate that nicotinic receptors are a novel target for development of antidepressants. This development is now under way.