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Annotation

Prata DP, Mechelli A, Fu CH, Picchioni M, Kane F, Kalidindi S, McDonald C, Howes O, Kravariti E, Demjaha A, Toulopoulou T, Diforti M, Murray RM, Collier DA, McGuire PK. Opposite effects of catechol-O-methyltransferase Val158Met on cortical function in healthy subjects and patients with schizophrenia. Biol Psychiatry . 2009 Mar 15 ; 65(6):473-80. PubMed Abstract

Comments on Paper and Primary News
Primary News: MTHFR, COMT Genes Work Together to Bring Down Cortical Activation in Schizophrenia

Comment by:  Jennifer Barnett (Disclosure)
Submitted 19 December 2008 Posted 19 December 2008

The recent studies of Prata and colleagues and Roffman and colleagues shed considerable further light on the ongoing mysteries of the catechol-O-methyltransferase Val158Met polymorphism and its effects on the proposed “inverted-U” shape of cortical dopamine function. Both study teams should be congratulated on these high-quality studies using what are, for neuroimaging experiments, impressive numbers of both patients and controls.

Our understanding of the effects of the COMT Val/Met polymorphism in humans remains incomplete despite no shortage of elegant studies and intriguing results. In their landmark 2001 paper, Egan and colleagues reported that Val carriers showed poorer cognitive function, a higher risk for schizophrenia, and reduced prefrontal efficiency when compared with Met carriers. These associations, along with a multitude of other psychological and psychiatric phenotypes, have since been tested in labs across the world. Meta-analyses of the available data have concluded that there is little influence of the Val/Met polymorphism on risk for schizophrenia (  Read more


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Primary News: MTHFR, COMT Genes Work Together to Bring Down Cortical Activation in Schizophrenia

Comment by:  S.H. Lin
Submitted 15 January 2009 Posted 19 January 2009
  I recommend this paper

The “inverted-U” shape of cortical dopamine function with regard to the COMT Val158Met polymorphism is an interesting issue worthy of discussion. The COMT enzyme may modulate the balance of tonic and phasic dopamine function depending on the area-specific neurochemical environment (Bilder et al., 2004). There is thought to be a complex nonlinear relationship between dopamine availability and brain function (Williams et al., 2007).

Our study (Liao et al., 2008) examined the relationships of three COMT SNPs—rs737865 in intro 1, rs4680 in exon 4 (Val158Met), and downstream rs165599—to schizophrenia and its related deficits in neurocognitive function in families of patients with schizophrenia in Taiwan. The study results indicated that the Val allele was associated with better performance on the WCST (i.e., greater Categories Achieved and Conceptual Level Response and fewer Perseverative Errors) or CPT (i.e., greater d'), which...  Read more


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