Effect of variation in BDNF Val(66)Met polymorphism, smoking, and nicotine dependence on symptom severity of depressive and anxiety disorders.

BACKGROUND: Smoking, especially nicotine dependence is associated with more severe symptoms of depression and anxiety disorders. However, the mechanisms underlying this association are unclear. We investigated the effect of brain-derived neurotrophic factor (BDNF) Val(66)Met polymorphism on the severity of depressive and anxiety symptoms in never-smokers, former smokers, non-dependent, and nicotine-dependent smokers with a current diagnosis of depression and/or anxiety.

METHODS: Patients with depressive or anxiety disorders and with available BDNF Val(66)Met polymorphism data (N=1271) were selected from Netherlands Study of Depression and Anxiety (NESDA). Dependent variables were severity of symptoms. Independent variables were smoking status and BDNF genotype. Age, sex, education, recent negative life events, alcohol use, body mass index, and physical activity were treated as covariates.

RESULTS: After controlling for covariates, nicotine-dependent smokers had more severe depressive symptoms than non-dependent smokers, former and never-smokers. The latter three groups did not differ in severity of depression. In Val(66)Val carriers, nicotine-dependent smokers had more severe symptoms of depression and anxiety than the other three groups, which were comparable in symptom severity. In Met(66) carriers, there were no group differences on severity of depression and anxiety. Nicotine dependence was the strongest predictor of severity of symptoms only in Val(66)Val carriers.

CONCLUSIONS: In patients with a current diagnosis of depression or anxiety, the relationship between nicotine dependence and symptom severity may be moderated by BDNF Val(66)Met. These results suggest that inherent genetic differences may be crucial for the worse behavioral outcome of nicotine, and that Val(66)Val carriers may benefit most in mental health from smoking cessation.