Catechol O-methyltransferase variants and cognitive performance in schizophrenia and bipolar disorder versus controls

Wirgenes, Katrine V.; Djurovic, Srdjan; Sundet, Kjetil; Agartz, Ingrid; Mattingsdal, Morten; Athanasiu, Lavinia; Melle, Ingrid; Andreassen, Ole A.

doi:10.1016/j.schres.2010.05.007

« Previous Next »Schizophrenia Research
Volume 122, Issue 1 , Pages 31-37, September 2010

Catechol O-methyltransferase variants and cognitive performance in schizophrenia and bipolar disorder versus controls

Katrine V. Wirgenes
- Institute of Psychiatry, University of Oslo, Oslo, Norway
- Department of Psychiatry, Oslo University Hospital— Ulleval, Oslo, Norway
Srdjan Djurovic
- Institute of Psychiatry, University of Oslo, Oslo, Norway
- Department of Medical Genetics, Oslo University Hospital — Ulleval, Oslo, Norway
- Department of Psychiatry, Oslo University Hospital— Ulleval, Oslo, Norway
Kjetil Sundet
- Institute of Psychology, University of Oslo, Oslo, Norway
Ingrid Agartz
- Institute of Psychiatry, University of Oslo, Oslo, Norway
- Department of Psychiatric Research, Diakonhjemmet Hospital, Oslo, Norway
Morten Mattingsdal
- Institute of Psychiatry, University of Oslo, Oslo, Norway
Lavinia Athanasiu
- Institute of Psychiatry, University of Oslo, Oslo, Norway
- Department of Medical Genetics, Oslo University Hospital — Ulleval, Oslo, Norway
- Department of Psychiatry, Oslo University Hospital— Ulleval, Oslo, Norway
Ingrid Melle
- Institute of Psychiatry, University of Oslo, Oslo, Norway
- Department of Psychiatry, Oslo University Hospital— Ulleval, Oslo, Norway
Ole A. Andreassen
- Institute of Psychiatry, University of Oslo, Oslo, Norway
- Department of Psychiatry, Oslo University Hospital— Ulleval, Oslo, Norway
- Corresponding author. Psychosis Research Section — TOP, Building 49, Division of Psychiatry, Oslo University Hospital — Ulleval, Kirkeveien 166, N-0407 Oslo, Norway. Tel.: +47 23 02 73 50; fax: +47 23 02 73 33.

Received 17 December 2009; received in revised form 14 April 2010; accepted 7 May 2010. published online 02 June 2010.

Abstract

Background

The gene encoding Catechol O-methyltransferase (COMT), a dopamine catabolic enzyme, is an important candidate gene in several psychiatric disorders. Several studies have shown an association between the functional Val¹⁵⁸Met polymorphism and cognitive performance. However, the results have been inconsistent and there are few studies addressing other COMT single nucleotide polymorphisms (SNPs).

Methods

We investigated SNPs across the whole COMT gene, including the Val¹⁵⁸Met polymorphism, for a putative effect on working memory, executive function and IQ in 315 patients with schizophrenia or bipolar disorder and 340 healthy controls.

Results

We replicated the association between the Val¹⁵⁸Met variant and working memory performance, and found a significant interaction between this SNP and diagnosis, with patients with schizophrenia showing a specific, reduced performance on the 2-back test. Several other COMT SNPs were associated with different cognitive functions, but did not remain significant after controlling for multiple testing. We also found significant interaction effects between the SNP variants and gender.

Conclusions

The present study replicates earlier findings showing an association between the functional Val¹⁵⁸Met polymorphism and working memory performance, with schizophrenia subjects particularly vulnerable. Furthermore, our findings suggest that other parts of the COMT gene seem to affect several related cognitive domains, which further support the notion that COMT is a modifier gene in prefrontal dopamine functioning.

Keywords: Catechol O-methyltransferase, Schizophrenia, Bipolar disorder, Neurocognition, Dopamine, Prefrontal cortex