177.4 Dopamine Glutamate Interactions in Patients With Schizophrenia
Year: 2017
Type: article
Study design: Observational Study
Abstract: 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. Methods: Patients with schizophrenia and matched healthy controls are imaged with both PET to measure dopamine release capacity and MRS to measure tissue glutamate. Glx data is obtained with a 3T system (GE MR750) and a PRESS TE = 80 ms pulse sequence. Subjects are matched for gender, ethnicity, age and familial SES. Patients are drug free or drug naive. Data acquisition is in progress. Results: So far a cohort of 10 patients with schizophrenia and 10 matched controls has been collected, but data acquisition is ongoing. We will examine group differences in Glx and in dopamine release in striatal and extrastriatal regions as well as correlations between both measures in the striatum and extrastriatal regions in both cohorts. Preliminary analysis indicates trend level associations between glutamate and abnormal dopamine release in the striatum, hippocampus, and medial prefrontal cortex, but these do not reach a level of statistical significance within the current sample. Conclusion: The convergence of dysfunction in dopamine and glutamate affects learning and poses a special challenge, as NMDA dysfunction may feed into the cortical dopaminergic dysfunction and vice versa, since dopamine modulates both pyramidal and GABAergic cells via D1 and D2 receptors to regulate the balance of excitation and inhibition in the prefrontal cortex. Our data raises the issue that one may not be corrected without addressing the other. Drugs that target both abnormalities are needed.
Source: Schizophrenia Bulletin
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W2602717459