Catechol-O-methyltransferase polymorphisms and some implications for cognitive therapeutics.
Catechol-O-methyltransferase (COMT) is a gene involved in the degradation of dopamine and may both increase susceptibility to develop schizophrenia and affect neuronal functions involved in working memory. A common variant of the COMT gene (val(108/158)met) has been widely reported to affect pre-frontally mediated working memory function, with the high-activity val allele associated with poorest performance across a number of tests sensitive to updating and target detection. Pharmacological manipulations of COMT val(108/158)met also have reliably produced alterations in cognitive function, in line with an inverted U function of prefrontal dopamine signaling. Furthermore, there is accumulating evidence that COMT val(108/158)met genotype may influence the cognitive response to antipsychotic treatment in schizophrenia patients, with met allele load predicting the greatest improvement with medication. Recently, other single-nucleotide polymorphisms (SNPs) across the COMT gene have emerged as possible risk alleles for schizophrenia, although little is known about whether they affect prefrontal cognition in a manner similar to COMT val(108/158)met. Preliminary evidence suggests a modest role for a SNP in the 5' region of the gene on select tests of attention and target detection. Haplotype effects also may account for a modest percentage of the variance in test performance, and are an important area for future study.
Diaz-Asper
Catherine M
CM
Clinical Brain Disorders Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland 20892, USA.
Weinberger
Daniel R
DR
Goldberg
Terry E
TE
D002394:Catechol O-Methyltransferase / Q000235:genetics*; D003071:Cognition / Q000502:physiology*; D003072:Cognition Disorders / Q000188:drug therapy*; D006801:Humans; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D017397:Prefrontal Cortex / Q000502:physiology / Q000503:physiopathology; D011401:Promoter Regions, Genetic
D002394:Catechol O-Methyltransferase