BackgroundRecent research suggests that the brain-derived neurotrophic factor (BDNF) may play a role in extinction learning. The goal of this study was to test whether variation in the BDNF Val66Met polymorphism is related to treatment response to exposure-based cognitive-behavior therapy (CBT), a form of extinction learning, in obsessive-compulsive disorder (OCD). MethodsOne hundred and six OCD patients from a specialized clinic, who underwent a standardized CBT treatment after partial or non-response to a 12-week pharmacological trial, were genotyped for the BDNF Val66Met and the relationship between genotype and treatment response was analyzed. ResultsAmong 98 CBT completers, 36% of those carrying the BDNF Met allele were rated as CBT responders compared to 60% of nonMet allele carriers (P=0.027). When analyzing the different obsessive-compulsive symptom dimensions, in patients with contamination/cleaning symptoms, the Met allele was associated with a significantly worse CBT response (P<0.0001) and a lower obsessions severity decrease from pre- to posttreatment (P=0.046). ConclusionGenetic variation in BDNF may be associated with treatment response in exposure-based CBT in OCD, especially in those patients exhibiting contamination/cleaning symptoms.