SOME SMOKERS USE NICOTINE TO "SELF-MEDICATE FOR DEPRESSION"
by Caryn Lerman, Ph.D., Neil Caporaso, M.D., David Main, MS, Janet Audrain, Ph.D. Neal R. Boyd, Ph.D., Elise D. Bowman, MS, and Peter G. Shields, M.D.
Behavioral research has established that cigarette smoking by people with depression can be a form of self- medication, using the mood-altering properties of nicotine to relieve -- at least temporarily -- depressive symptoms. Dr. Lerman suggests that depressed people --and nondepressed people -- who smoke to improve their mood may do so because of differences in their genetic make-up. Such differences that may be important to the effectiveness of future treatments for depression and nicotine dependency.
In their article "Depression and Self-Medication with Nicotine: The Modifying Influence of the Dopamine D4 Receptor Gene," psychologist Caryn Lerman, Ph.D., of the Georgetown University Medical Center, and her co-authors note that previous research has shown that people with a history of depression are significantly more likely to be smokers and be diagnosed as nicotine-dependent. Additionally, smokers are more likely than nonsmokers to report depressive symptoms and such symptoms predict relapse following attempts to quit smoking. "In fact," they point out, "the likelihood of quitting smoking is about 40 percent lower among depressed smokers compared with the likelihood among nondepressed smokers." The researchers' study was designed to determine if genes involved in the brain's reward mechanisms play a role in this phenomenon.
The researchers recruited 231 smokers who donated blood for genetic analysis and who were assessed for depressive symptoms, their level of nicotine dependence and the degree to which they smoked for stimulation or to counter negative affect (feeling down in the dumps). This has been referred to as "self-medication" smoking. A majority of the smokers (63 percent) were classified as nondepressed and 37 percent were classified as depressed.
The investigators were interested in one particular gene, the dopamine receptor D4 gene (DRD4) which is highly expressed in the areas of the brain involved in emotion and reward-seeking behaviors. The DRD4 gene comes in two forms: short and long. A given individual can have one form (S/S, L/L) or both (S/L). Among the study participants, 76 percent had S/S genotypes, 19 percent has S/L genotypes and only five percent had L/L genotypes.
After analyzing their data, the researchers found relationships among genotype, the presence or absence of depression and smoking behaviors: among depressed smokers, those with S/S genotypes were more likely to smoke for self-medicating purposes than those with either S/L or L/L genotypes.
Since depressed people appear to be predisposed to initiate smoking and to become highly nicotine-dependent, the authors suggest that smokers who report depression may, therefore, "derive significant benefit from nicotine replacement therapies and psychotropic medications." With additional research, they add, "genotyping may become a useful strategy for designing and targeting pharmacologic therapies to subgroups of depressed smokers most likely to benefit from them."
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