Effect of variation in BDNF Val66Met polymorphism, smoking, and nicotine dependence on symptom severity of depressive and anxiety disorders

Abstract

BackgroundSmoking, 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) Val66Met 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. MethodsPatients with depressive or anxiety disorders and with available BDNF Val66Met 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. ResultsAfter 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 Val66Val carriers, nicotine-dependent smokers had more severe symptoms of depression and anxiety than the other three groups, which were comparable in symptom severity. In Met66 carriers, there were no group differences on severity of depression and anxiety. Nicotine dependence was the strongest predictor of severity of symptoms only in Val66Val carriers. ConclusionsIn patients with a current diagnosis of depression or anxiety, the relationship between nicotine dependence and symptom severity may be moderated by BDNF Val66Met. These results suggest that inherent genetic differences may be crucial for the worse behavioral outcome of nicotine, and that Val66Val carriers may benefit most in mental health from smoking cessation.