Fig. 4.

Data from preclinical models and schizophrenia imaging/postmortem findings suggest that the site of deficit in the schizophrenia brain likely involves a decreased PV interneuron inhibition of pyramidal neurons in the limbic hippocampus. Current therapeutic approaches to schizophrenia rely on blocking DA receptors in the associative striatum to attenuate the impact of DA system overdrive. However, blocking D2 receptors is acting 5 synapses downstream from where we believe the deficit driving schizophrenia is located. As a result, it is not surprising that D2 antagonist antipsychotic drugs are not as efficacious as one that targets diminished inhibition in the limbic hippocampus.