Posted by stjames on June 16, 2001, at 1:27:00
Dopamine-Catabolizing Gene Variant Associated With Schizophrenia
--------------------------------------------------------------------------------WESTPORT, CT (Reuters Health) May 31 - A functional polymorphism of catechol-O-methyltransferase (COMT) gene compromises prefrontal cortical function and increases a carrier's susceptibility to schizophrenia. Dr. Michael F. Egan, of the National Institute of Mental Health, in Bethesda, Maryland, and colleagues describe these findings in the Proceedings of the National Academy of Sciences for June 5.
"This is the first detailed mechanism describing how a specific alteration in a specific gene affects brain function and thereby increases risk for schizophrenia," Dr. Egan told Reuters Health. "We used a new approach to help us find this gene. While most studies compare subjects based on whether they have schizophrenia, we added several measures of prefrontal function," he added.
According to the authors, the gene for COMT, which catabolizes dopamine, contains a missense mutation that results in the substitution of Met for Val at codon 108/158. The enzyme containing Val has four times the activity of the Met variant.
The investigators genotyped 175 patients with schizophrenia, 219 healthy siblings, and 55 control subjects. The subjects were tested for prefrontal executive cognition using the Wisconsin Card Sorting Test.
Patients and their siblings scored significantly worse on the card sorting test than did control subjects. Furthermore, those with the Val/Val genotype scored worse than those with the Val/Met and Met/Met genotypes. The investigators estimate that the COMT genotype accounted for 4.1% of the variance in performance on the test. The significance of the association remained high after adjustment for gender, diagnosis, age, and education.
"Probably the most important and direct implication of this finding is that currently available medications that inhibit COMT may improve cognition and perhaps reduce illness severity in patients with one or two copies of this gene," Dr. Egan told Reuters Health.
"We hope to test this medication as soon as possible with a new study we are about to begin," he added.
Proc Natl Acad Sci 2001;98:6917-6922.
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