Clues about how a suspect version of a gene may slightly increase risk for schizophrenia are emerging from a brain imaging study by the National Institutes of Healths (NIH) National Institute of Mental Health (NIMH). The gene variant produced a telltale pattern of activity linked to production of a key brain messenger chemical.
Areas in prefrontal cortex where blood flow (yellow) was linked to midbrain dopamine synthesis, in opposite directions in subjects with val and met COMT gene type. PET data is superimposed on 3-D MRI view of brain. Source: NIMH Clinical Brain Disorders Branch
An inverted "U" models the relationship between COMT gene type, prefrontal cortex activity, and prefrontal dopamine levels. The cortex functions optimally when dopamine activity is neither too low nor too high, corresponding to the top of the curve. Dopamine is thought to "tune" prefrontal neurons by regulating signal-to-noise ratios - but in opposite directions, depending on whether an individual has inherited the val or met COMT gene type. Source: NIMH Clinical Brain Disorders Branch
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 NIMHs 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.
Jules Asher | EurekAlert!
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