Influence of Brain Derived Neurotrophic Factor and Family History of Alcohol Dependence on Alcohol Use in Healthy Social Drinkers
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Brain-derived neurotrophic factor (BDNF) is important for neuronal survival, differentiation and consolidation of synaptic strength. Studies have found increased alcohol use and genetic risk for alcohol dependence in individuals with the Val66Met single-nucleotide polymorphism (SNP) of the BDNF gene, a genotype associated with decreased activity-dependent release of BDNF. However, the literature remains contentious with regard to this issue. The current study was designed to address this issue with two aims. Aim 1 examined the influence of the Val66Met SNP and family history of alcohol dependence (FH) on alcohol use in healthy social drinkers. It was expected that the Val66Met polymorphism would be associated with higher drinking levels compared to the Val66Val genotype, and those participants with a combination of Val66Met genotype and a positive FH would exhibit the most severe alcohol use profile. Results for Aim 1 indicated no significant effects of genotype on quantity/frequency of alcohol use; however, the Val66Met group had an earlier age at first alcohol use. FH-positive participants had an earlier age at first drunken episode. There were no interactions of BDNF genotype x FH group. Correlational analyses revealed that quantity/frequency of alcohol use was positively related to perceived stress levels in the Val66Met group, such that participants with higher stress levels tended to consume more alcohol. This relationship was not present in the Val66Val group. Aim 2 examined stress-related changes in serum BDNF levels. It was expected that Val66Met and Val66Val groups would have different stress-related changes in serum BDNF levels, and that the profile of the Val66Met group would be associated with more severe alcohol use. Results of Aim 2 indicated that, across groups, serum BDNF levels decreased in response to stress, but there were no main effects or interactions of BDNF genotype or FH group. However, in the Val66Met group, stress-related BDNF change (post- minus pre-stress) was related to age at first drink, such that earlier age of alcohol use was associated with a greater stress-related decrease in serum BDNF. This relationship was not present in the Val66Val group. Taken together, the results of these two aims suggest that in healthy young social drinkers, the association between the Val66Met SNP and alcohol use may be linked to stress vulnerability and behavioral risk factors (i.e., earlier initiation of alcohol use), which are known to be associated with the development of alcohol dependence.