Low activity of the COMT gene is associated with obsessive-compulsive disorder, as well as schizophrenia.
Catechol-O-Methytransferase (COMT) catalyzes O-methylation, a major step in the degradation of catecholamines – including the neurotransmitters dopamine, epinephrine, and norepinephrine. Clearing dopamine from synapses is a major effect of COMT. Low activity of the COMT gene is associated with obsessive-compulsive disorder, as well as schizophrenia. COMT is the strongest schizophrenia candidate among approximately 27 genes in a 1.5-3 million nucleotide region of chromosome 22 that is deleted in velo-cardio-facial syndrome (VCFS). About 20% of VCFS patients have schizophrenia or psychosis. Deletion of the COMT gene on one chromosome may work in combination with valine substitution at amino acid position 158 of the gene that significantly lowers enzyme activity. The lack of dopamine transporters in the cortex may accentuate the effect of the valine polymorphism, with its diminished ability to clear dopamine.
The basal ganglia, a group of interconnected brain areas located deep in the cerebral cortex, have proved to be at work in learning, the formation of good and bad habits, and some psychiatric and addictive disorders.