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Adolescent alcohol use demonstrates distinct developmental trajectories with dissimilar times of onset and trajectories. Given the importance of brain-derived neurotrophic factor (mature BDNF) in this development stage, the current study investigated its relationship with alcohol use. It also extends the literature by assessing the role of its precursor (pro-BDNF). Therefore, over the span of 5 years, we enrolled and followed participants to define age-related changes in BDNF levels in healthy adolescents. Then, the onset and frequency of alcohol use from ages 11 to 18 were collected to determine how the relationship between alcohol, pro-BDNF, and m-BDNF unfolds over time. With respect to development, analyses demonstrated that BDNF concentration slowly increases throughout adolescence. However, despite having similar basal BDNF levels, compared to controls, adolescents that started drinking before 15 years of age always exhibited lower BDNF levels. They also had a significant decrease in pro-BDNF levels. On the other hand, levels of mature BDNF steadily increased (974.896±275 pg/ml) in those starting alcohol use after the age of 15. Similar to the younger users, a significant drop in pro-BDNF levels was observed over the course of the study. Our results suggested that both pathways may participate in the complex processes of alcohol dependence. The findings highlight the relevance of assessing alcohol-associated changes across the different phases of this vulnerable developmental period. This is the first study evidencing that m-BDNF changes associated with drinking behaviors differed between young and older adolescents. It is also the first article, documenting that drinking during adolescence leads to long-term decreases in pro-BDNF. These results have important implications for policies and programs targeting alcohol use disorders.

Among Adolescents, BDNF and Pro-BDNF Lasting Changes with Alcohol Use Are Stage Specific