A recent meta-analysis concluded that the Val/Val genotype may be a risk factor for developing nicotine addiction (9). While some studies reported an association between the Val/Val genotype and poor response to smoking cessation treatments (11–13), other studies did not confirm these results, and some studies reported opposite findings (14, 15). Surprisingly, only a few studies have investigated the potential mechanism by which the COMT Val158Met polymorphism may modulate the risk for and treatment response to nicotine addiction. In a functional MRI study, abstinent smokers with the Val/Val genotype performed worse on the n-back test, which measures working memory (16). Furthermore, abstinent smokers with the Val/Val genotype had greater blood flow increases in brain areas associated with cigarette craving (17). These findings suggest that smoking cessation may be particularly difficult for smokers with the Val/Val genotype. However, systematic studies examining the COMT Val158Met polymorphism on withdrawal severity and nicotine responses are lacking. Such studies may provide better insight into the mechanisms of the observed COMT Val158Met effects on nicotine dependence.
