ABSTRACT
BACKGROUND: Associations between the well-known functional single nucleotide polymorphism Val (158)Met in the gene encoding catechol- O-methyltransferase (COMT) and cognitive do-mains affected in schizophrenia are inconsistent regarding directionality and specific impact and call for a more fundamental cognitive endophenotype. Recent studies suggest that the COMT genotype contributes to cognitive flexibility, a fundamental cognitive ability that potentially influences an individual's performance in a variety of other neurocognitive tasks. METHODS: We investigated the association between COMT Val (158)Met genotype and cognitive flexibility as assessed by signal discrimination in the Continuous Performance Test - Identical Pairs version in a cohort of 111 German schizophrenic patients. RESULTS: COMT genotype was significantly associated with signal discrimination index d' in schizophrenia. The Val/Val genotype was associated with the highest and the Met/Met genotype with the lowest scores; heterozygous individuals displayed an intermediate performance. CONCLUSIONS: Our data suggest that allelic variation at the COMT Val (158)Met locus may influence signal discrimination capacity in schizophrenia and confirm that Val loading, probably due to decreased prefrontal dopamine availability, is associated with greater cognitive flexibility, which in turn may influence other cognitive measures that have been associated with COMT to date.