The functional Val158Met polymorphism in catechol-O-methyltransferase (COMT) is associated with depression and motivation in men from a Swedish population-based study

Background: Environmental risk factors together with genetic vulnerability create a complex background to develop depression. Methods: We investigated the associations between COMT Val(158)Met and depression in a Swedish population-based sample of 405 depressed individuals (major depression diagnosis, dysthymia or mixed anxiety depression defined according to DSM-IV) and 2,151 healthy controls. We also analyzed interaction between this genetic variation and some environmental risk factors for depression and the link between this polymorphism and the low motivational level and negative mood state found in depressed individuals. Results: Depressed individuals displayed a higher frequency of the Met/Met and Met/Val genotypes compared to controls (OR = 1.49, CI95% = 1.11-2.00, P = 0.009). The association was found among men only (OR = 2.26, CI95% = 1.26-4.05, p = 0.008). Regression analysis including some potential risk factors for depression, did further indicate that Met/Met and Met/Val were associated with depression in men (P = 0.005). There was also an interaction between genotype and family childhood problems (RERI = 0.876, CI95% = 0.090-1.662 and AP = 0.426, CI95% = 0.030-0.821). Further, depressed men homozygous for the Val-allele, had a higher motivational level than depressed men with a Met-variant (P = 0.02). Limitations: The sample size of depressed individuals per group when stratifying cases according to gender and genotypes is considered a limitation. Conclusions: The Met-variants of COMT Val(158)Met are risk variants for depression and low motivational level in depressed Swedish men, but not women. Individuals with this risk variant in combination with a problematic childhood, have an even higher risk to develop depression. (C) 2010 Elsevier B.V. All rights reserved.