Genetic Dissection of Dopamine-Mediated Prefrontal-Striatal Mechanisms and Its Relationship to Schizophrenia

This chapter examines findings through which heritable human neuroimaging intermediate phenotypes could provide a window to examine genetic mechanisms of active prefrontal cognitive processing related to dopamine (DA). Genetic variation influencing task-related prefrontal cortical function was consistent with fundamental predictions based on the biology of DA tuning in cortical microcircuits. These findings also extended the basic biological data to implicate molecules impacting variation in active human brain function, potentially mirroring component disease-related brain processes in schizophrenia. The findings of interacting genetic elements consistent with the cross-talk within and across DA and glutamatergic systems, and their intracellular signaling pathways, arguably contribute further empirical validation to the strategy to identify molecules whose genetic variation could be of substantial combined influence on human brain function at the network or systems level.