Journal
MOLECULAR PSYCHIATRY
Volume 10, Issue 3, Pages 287-298Publisher
SPRINGERNATURE
DOI: 10.1038/sj.mp.4001616
Keywords
endophenotype; dopamine; MRI; candidate gene; association study; PET
Funding
- NIMH NIH HHS [MH43271, MH40856, MH31593] Funding Source: Medline
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The catechol-O-methyl transferase ( COMT) gene is considered a leading schizophrenia candidate gene. Although its role in increasing schizophrenia susceptibility has been conflicting, recent studies suggest the valine allele may contribute to poor cognitive function in schizophrenia. (VM)-M-158 COMT genotype was obtained on 159 schizophrenia patients and 84 healthy controls. The effects of COMT genotype on four measures of working memory/executive functions (Wisconsin Card Sorting, digit span backward, Trail Making and N-back tests) and on MRI frontal brain volumes were examined. Genotype distributions were not significantly different between patients and controls. There were no significant genotype or genotype-by-group effects on any working memory/executive function measures. No genotype or genotype-by-diagnosis interaction effects were found with MRI frontal lobe volumes. Randomization analyses using [O-15]H2O positron emission tomography ( PET) cerebral blood flow data found Val/Val patients had higher frontal lobe activation than Met/Met patients while performing the one-back task. Overall, these findings do not support a major role for COMT in increasing susceptibility for schizophrenia or in mediating frontal lobe function. Age-related changes and phenotypic heterogeneity of schizophrenia may influence the complex relationships between COMT genotype and cognition.
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