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Introduction: Contemporary cognitive models emphasize the importance of certain dysfunctional beliefs in the development and maintenance of Obsessive-Compulsive Disorder (OCD): overimportance of thoughts, need to control thoughts, perfectionism, intolerance of uncertainty, inflated responsibility, and overestimation of threat. Although a recent twin study suggests that these dysfunctional beliefs are significantly heritable, there have been no previous attempts to analyze candidate genes associated with them. Objectives: Our study aimed to investigate the possible association between OC-related dysfunctional beliefs and variants of two functional polymorphisms of the COMT (Val158Met) and BDNF (Val66Met) genes in 141 OCD patients. Methods: The non-synonymous mutation Val158Met (rs4680) in the COMT gene and the Val66Met functional variant (rs6265) in the BDNF gene were genotyped with the KASPar assay system. The validated Spanish short version of the Obsessive Beliefs Questionnaire, (OBQ-44), was used to assess dysfunctional beliefs. Multivariate analysis of covariance (MANCOVA) and a post hoc one-way analysis of covariance (ANCOVA) were perfomed. Results: Variability in dysfunctional beliefs was not affected by the COMT or BDNF genotype when examining the two genes in isolation, but we detected a significant COMT x BDNF interaction effect on responsibility and overestimation of threat scores. These cognitive distortions were significantly higher among OCD subjects with the BDNF Met-present genotype who were also carriers of the COMT Val/Met and Met/Met genotypes. Conclusions: Our data suggest that an interaction between dopaminergic and neurotrophic functional gene variants influences some of the dysfunctional belief domains hypothesized to contribute to the etiology of OCD. [ABSTRACT FROM AUTHOR]