The study found that increased activity in the front of the brain predicted increases in the neurotransmitter dopamine in the middle of the brain in subjects with the suspected schizophrenia-related version of the gene. Yet, the opposite relationship held for subjects with the other of two common versions of the gene.
"A tiny variation in the gene that makes the enzyme that breaks down dopamine causes a complete flipflop not a mere difference in degree in dopamine activity in these two brain areas," explained NIMH's Dr. Andreas Meyer-Lindenberg, who, along with Dr. Karen Berman and colleagues, reported their findings in the April 10, 2005 online edition of Nature Neuroscience.
The NIMH study also for the first time confirms in living humans that activity of the front brain area, the prefrontal cortex, is regulated by dopamine production in the midbrain, which, in turn, is regulated by these two common gene variants.
Schizophrenia, a severe mental illness marked by hallucinations and delusions, affects one percent of the population and is treated with antipsychotic drugs that block dopamine. The prefrontal cortex is critical for motivation, learning in response to reward, and working memory functions impaired in schizophrenia, which is thought to involve a dopamine imbalance.
Individuals inherit two copies (one from each parent) of the gene for the enzyme catecho-O-methyltransferase (COMT), which chemically breaks down dopamine. It comes in two versions, val and met, so a person can have two of the same version or one of each. Since it results in considerably weaker enzyme action, people with th
Contact: Jules Asher
NIH/National Institute of Mental Health