to lower synaptic DA levels in the prefrontal cortex (Chen et al. 2004). Thus there is a strong prior hypothesis that implicates DA regulation in prefrontal cortical function, and particularly that variation in COMT genotype could be associated with an endophenotype of schizophrenia, even if it is not associated with schizophrenia case status (Munafo et al. 2005). Consequently a number of investigators have carried out genetic studies of COMT genotype and cognitive function. These studies allow us to compare the effect sizes observed in case-control studies of psychiatric disease with those observed in endophenotype studies.
