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Outcomes from extinction therapy for anxiety (Biol Psychiatry 2009; 66:636) have been associated with a polymorphism at codon 66 of the gene for brain-derived neurotrophic factor (BDNF) that leads to a valine (Val) to methionine (Met) substitution (Val66Met). In mice, presence of the Met allele was associated with slower extinction of fear, which was rescued by d-cycloserine. d-cycloserine, which acts at the glycine site of the N-methyl-d-aspartate receptor (J Neurosci 2009; 29:4056), has been used to augment the treatment of anxiety in humans (JW Psychiatry Jan 14 2008). To build on these data, researchers performed animal and human studies.
Mice with knocked-in human Val or Met alleles were conditioned to fear (i.e., an adverse stimulus wa…