Genetic modulation of PFC coupling between different areas implicated in working memory circuits has also been explored in imaging genetics paradigms with interesting results (e.g. modulation of DLPFC-HF and DLPFC-PFC coupling by ZNF804A [10 ··]; DLPFC or VLPFC coupling with parietal cortex by COMT-GRM3 epistasis [31]). These circuit based associations involve more complex and likely realistic measures of brain function, but PFC coupling with other regions as an intermediate phenotype related to risk for schizophrenia has not been demonstrated yet and requires further exploration. Moreover, in some reports, engagement of the prefrontal cortex may be modulated in different ways by genes based on diagnosis (patients with schizophrenia versus normal controls) [29, 32]. These findings are not easily interpreted, because while they suggest complex gene by disease modulation, they can also be driven by confounders related to disease-state factors, such as gene by medication interactions.
