COMT and schizophrenia: Tan et al (2007) further showed that an epistatic genetic interaction of risk variants for schizophrenia involving the cortical glutamate and dopamine systems revealed similar regions of activation as seen here in healthy controls carrying PRODH risk variants but in the opposite direction with the two risk variants in COMT and GRM3 showed increased engagement of the parietal cortex and VLPFC while PRODH risk haplotype showed an increase in striatal activity and decrease in activation of the parietal lobe and VLPFC [38].