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COMT val108/158met genotype, cognitive function, and cognitive improvement with clozapine in schizophrenia
Neil D Woodward1, Karu Jayathilake, Herbert Y Meltzer
1Department of Psychology, Vanderbilt University, Nashville, TN 37203, USA. neil.woodward@vanderbilt.edu
Schizophrenia Research
|November 25, 2006
Summary
The COMT val108/158met gene variant impacts cognitive function in schizophrenia. Certain genotypes showed greater improvement in attention and verbal fluency after clozapine treatment.
Area of Science:
- Neuroscience
- Psychiatry
- Genetics
Background:
- The catechol-O-methyltransferase (COMT) enzyme regulates dopamine in the prefrontal cortex.
- A specific COMT gene variant (val108/158met SNP) is linked to cognitive function in schizophrenia.
- Previous studies show mixed results, possibly due to sample size and medication status.
Purpose of the Study:
- To investigate the association between COMT val108/158met genotype and cognitive function.
- To examine how this genotype influences cognitive improvement with clozapine treatment in schizophrenia patients.
Main Methods:
- A prospective study of schizophrenia patients, mostly unmedicated.
- Genotyping for the COMT val108/158met SNP.
- Cognitive testing at baseline, 6 weeks, and 6 months during clozapine treatment.
Main Results:
- Baseline association found between COMT genotype and executive function/working memory.
- Met homozygous and val/met heterozygous patients showed greater improvement in attention and verbal fluency after 6 months of clozapine.
- Val homozygous patients showed less improvement.
Conclusions:
- The COMT val108/158met genotype influences baseline cognition and response to clozapine.
- Findings support the role of COMT genotype in cognitive outcomes for schizophrenia patients treated with atypical antipsychotics.
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