Serotonin transporter and BDNF polymorphisms interact to predict trait worry

Background and Objectives: Excessive worry is associated with a range of psychological disorders. While previous studies have examined genes associated with a range of different anxiety phenotypes, none have explored genes specifically associated with the general tendency to worry. Design: The present study tested associations between trait worry and functional polymorphisms of three candidate genes: the serotonin transporter-linked polymorphic region (5-HTTLPR) of the SLC6A4 gene, the Val66Met region of the brain-derived neurotrophic factor (BDNF) gene, and the Val158Met region of the catechol-O-methyltransferase (COMT) gene. Methods: A heterogeneous sample of adult participants (n = 173) completed the Penn State Worry Questionnaire (PSWQ) and provided DNA samples for genotyping. Results: Results revealed a significant interaction between 5-HTTLPR and BDNF genotypes predicting levels of worry. Specifically, there was a significant positive association between 5-HTTLPR short alleles and PSWQ scores, but only in BDNF met allele carriers. COMT genotype was not significantly associated levels of worry, nor did COMT interact with 5-HTTLPR or BDNF genotypes to predict PSWQ scores. Conclusions: These findings provide preliminary evidence about the putative genetic etiology of worrying. Key limitations of the present study and corresponding directions for future research on this topic are discussed.