['Variations within the catechol-O-methyltransferase (COMT) gene have been associated with pain severity in temporomandibular disorders (TMDs). Psychological factors such as personal conflicts, life stress and depression, are well known to be associated with onset, severity and chronicity of pain disorders.', 'We hypothesized that the relationship between the COMT gene and TMD pain is modified by depressive symptoms.', 'Cross-sectional data from the population-based Study of Health in Pomerania (SHIP) in Germany were used to estimate additive interactions between depressive symptoms and 22 single-nucleotide polymorphisms (SNPs) of the COMT gene and the neighbouring thioredoxin reductase 2 (TXNRD2) gene on TMD pain. All participants were Caucasian subjects from a rural area in Northeast Germany. After exclusion of 79 subjects with antidepressant medication, 29.9% of the remaining 3904 subjects reported lifetime depressive symptoms. TMD pain was assessed by a standardized clinical examination. Among various TMD signs, only those that assessed muscle or joint pain on palpation were used as recommended.', 'Six SNPs from the first of three COMT/TXNRD2 haploblocks interacted with depressive symptoms on TMD pain (smallest p-value: 2.7 × 10(-10) ). In subjects without depressive symptoms, rs5993882 was identified as the SNP most likely to be related to TMD pain. In subjects with symptoms of depression, rs1544325 was the corresponding top COMT SNP.'] Is the effect of catechol-O-methyltransferase polymorphisms on pain modified by depressive symptoms?