NeuroRX

, Volume 3, Issue 1, pp 97–105

Catechol-O-methyltransferase polymorphisms and some implications for cognitive therapeutics

  • Catherine M. Diaz-Asper
  • Daniel R. Weinberger
  • Terry E. Goldberg
Article

Abstract

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 (val108/158met) has been widely reported to affect prefrontally 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 val108/158met 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 val108/158met 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 val108/158met. 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.

Key Words

Catechol-O-methyltransferase COMT working memory executive function prefrontal cognition 

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Copyright information

© The American Society for Experimental NeuroTherapeutics, Inc 2006

Authors and Affiliations

  • Catherine M. Diaz-Asper
    • 1
  • Daniel R. Weinberger
    • 1
  • Terry E. Goldberg
    • 1
  1. 1.Clinical Brain Disorders Branch, National Institute of Mental HealthNational Institutes of HealthBethesda
  2. 2.Division of Psychiatry ResearchZucker Hillside HospitalGlen Oaks

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