The study investigates the impact of the BDNF (Val66Met) polymorphism on anxiety-related behavior. BDNF, a key neurotrophic factor, is associated with alterations in brain anatomy and memory, but its role in clinical disorders is unclear. The researchers generated a variant BDNF mouse (BDNFMet/Met) that mimics the human phenotype. BDNFMet was expressed at normal levels in the brain but showed defective secretion from neurons. BDNFMet/Met mice exhibited increased anxiety-related behaviors, which were not normalized by the antidepressant fluoxetine. These findings suggest that the BDNF polymorphism may play a significant role in genetic predispositions to anxiety and depressive disorders. The study also highlights the potential of BDNFMet/Met mice as a model to identify novel pharmacological approaches for treating anxiety disorders.The study investigates the impact of the BDNF (Val66Met) polymorphism on anxiety-related behavior. BDNF, a key neurotrophic factor, is associated with alterations in brain anatomy and memory, but its role in clinical disorders is unclear. The researchers generated a variant BDNF mouse (BDNFMet/Met) that mimics the human phenotype. BDNFMet was expressed at normal levels in the brain but showed defective secretion from neurons. BDNFMet/Met mice exhibited increased anxiety-related behaviors, which were not normalized by the antidepressant fluoxetine. These findings suggest that the BDNF polymorphism may play a significant role in genetic predispositions to anxiety and depressive disorders. The study also highlights the potential of BDNFMet/Met mice as a model to identify novel pharmacological approaches for treating anxiety disorders.