176. Hyperglutamatergia and Bioenergetic Metabolism in Schizophrenia: Next Generation of Studies
Year: 2017
Type: conference-abstract
Abstract: Overall Abstract: Pharmacologic, genetic, postmortem, and imaging studies have firmly established schizophrenia as a disorder of excitatory synapses. Consistently, the first generation of H-MRS studies with single voxels and lower field strengths have mostly confirmed subtle increases in brain glutamate. However, the translational effort linked to this body of research has been disappointing with no efficacious glutamatergic drugs identified so far. A renewed effort to understand the spatial distribution, timing, clinical correlates, and underlying mechanisms of glutamatergic dysfunction is warranted. Hence, we present a new generation of studies with various methodological advances: broad spatial imaging of glutamate (proton echo planar spectroscopic imaging at 3T), improved spectral resolution of glutamate metabolites and lactate (H-MRS at 7T), dynamic assessment of phosphoenergetics and its relationship with glutamate (31P MRS at 4T) as well as postmortem and animal model investigations of the molecular bioenergetics of the glial/synaptic units. These studies provide converging evidence that early in schizophrenia, there is a cortical hyperglutamatergic process, linked to a fundamental shift toward anaerobic metabolism, alteration in the lactate shuttle with accumulation of lactate, and decreased availability of ATP, which accounts for part of the cognitive and functional deficits that persist, despite dopamine D2 blockade provided by standard treatment. The implications from these data, for the development of novel pharmacological strategies, will be discussed.
Source: Schizophrenia Bulletin
Author: Juan Bustillo
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W2600127712