Glutamatergic basis of antipsychotic response in first-episode psychosis: a dual voxel study of the anterior cingulate cortex

Research Square (Research Square)(2023)

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摘要
Abstract Treatment-resistant schizophrenia is believed to be related to excess prefrontal glutamate. If we can identify these individuals early in the course of illness, the repeated use of first-line antipsychotics can be reduced and first-episode patients can be stratified for accelerated treatments. The use of proton magnetic resonance spectroscopy (1H-MRS) to measure glutamate and Glx (glutamate plus glutamine) provides a means for such a stratification, but we must first establish if there is robust evidence linking elevations in anterior cingulate cortex (ACC) glutamate metabolites to poor response, and determine if continuous exposure to antipsychotics worsens the glutamatergic excess in eventual non-responders. In this study, we estimated glutamate levels at baseline in 70 drug-naive patients with schizophrenia. We then treated them (N=42) with risperidone and followed them up for 3 months to categorize their response status. We hypothesized to see “hyperglutamatergia” at baseline in later non-responders and expected this to worsen with treatment. Non-responders had high glutamate before treatment-onset (F1,79=3.20, p=0.046, partial η2 = 0.075); However, glutamate levels did not change significantly over time in both non-responders and responders over the 3 months of treatment (F1,31=1.26, p=0.270, partial η2 = 0.039). Antipsychotic use without prior knowledge of later response delays symptom relief in a subgroup of first-episode patients, but does not worsen the glutamatergic excess seen at baseline. Given the current practice of non-stratified use of antipsychotics, longer-time follow-up MRS studies are required to see if improvement in symptoms accompanies a shift in glutamate profile.
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关键词
antipsychotic response,anterior cingulate cortex,glutamatergic basis,dual voxel study,first-episode
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