177.4 Dopamine Glutamate Interactions in Patients With Schizophrenia

Background: Converging evidence suggests concomitant abnormalities in NMDA-dependent processes in schizophrenia in addition to dopaminergic disturbances. These include the robust and replicable deficits in mismatch negativity (MMN), an NMDA-dependent event-related potential to unexpected auditory events, and MR spectroscopy findings showing increased glutamate in untreated SCZ in several cortical and subcortical regions (thalamus, striatum, hippocampus, and medial prefrontal cortex). Studies of medicated patients have shown a glutamate- or glutamine-lowering effect of antipsychotic medications. We also recently measured a deficit in cortical dopamine release using PET and the amphetamine challenge. Taken together these findings suggest that dopamine and glutamate may be both affected in the cortex and raise a special therapeutic challenge. Furthermore, in the striatum glutamate and dopamine have both been found to be abnormal.