Altered glutamate level and its association with working memory among patients with treatment-resistant schizophrenia (TRS): a proton magnetic resonance spectroscopy study.

Muhammad Abdullah,Yen Kuang Yang,Kao Chin Chen,Shih-Hsien Lin,Li-Chung Huang,Huai-Hsuan Tseng

doi:10.1017/s003329172100533x

Abstract

Treatment-resistant schizophrenia (TRS) and non-TRS may be associated with different dopaminergic and glutamatergic regulations. The concept of dysregulated glutamatergic concentrations in specific brain regions remains controversial. Herein, we aimed to assess (i) the distribution of the glutamatergic concentration in the brain, (ii) the association between working memory (WM) differences in TRS and non-TRS patients, and (iii) whether an alteration in the glutamate (Glu) level is associated with WM. The participants included 38 TRS patients, 35 non-TRS patients, and 19 healthy controls (HCs), all of whom underwent 1.5-Tesla proton magnetic resonance spectroscopy of anterior cingulate cortex (ACC) and medial prefrontal cortex (MPFC). The ratios of glutamatergic neurometabolites to N-acetylaspartate + N-acetyl aspartylglutamate (NAAx) were calculated. Cognitive function was assessed using the Wechsler Adult Intelligence Scales, 4th Edition, which included the working memory index (WMI). The TRS patients had a higher glutamate + glutamine (Glx)/NAAx ratio compared to the non-TRS patients and HCs in the ACC, but this was not significantly different in the MPFC. WM was negatively correlated with Glx/NAAx in the ACC among the non-TRS patients, but not in the TRS patients or HCs. Our findings were consistent with most studies indicating that the glutamatergic concentration in the ACC plays important roles in the classification of TRS and cognition. Our results may provide potential evidence for predictors and treatment response biomarkers in TRS patients. Further research is needed to probe the value using the relationship between Glu and WM as a potential prognostic predictor of schizophrenia.

Highlights

Schizophrenia, a neurodegenerative disorder with functional decline, may become a burden on patients and their families, and results in increased medical costs and negative effects on public health (Charlson et al, 2018; McCutcheon, Marques, & Howes, 2020)
General tendencies toward an older age, a lower educational level, poorer clinical outcomes, and poorer working memory (WM) were noted among the patient groups, especially the Treatment-resistant schizophrenia (TRS) patients
Regarding the concentrations of neurometabolites (Table 2), higher Glx/NAAx in the anterior cingulate cortex (ACC) area was found in the TRS group in comparison with the non-treatment-resistant schizophrenia (non-TRS) group; this difference remained even after adjustment for covariates

Summary

Introduction

Schizophrenia, a neurodegenerative disorder with functional decline, may become a burden on patients and their families, and results in increased medical costs and negative effects on public health (Charlson et al, 2018; McCutcheon, Marques, & Howes, 2020). Considering that first- and second-generation antipsychotic agents are mostly based on the dopaminergic hypothesis, glutamate neurometabolites might play another critical role in major psychiatric disorders, especially in schizophrenia and TRS (Li, Yang, & Lin, 2019). We aimed to assess (i) the distribution of the glutamatergic concentration in the brain, (ii) the association between working memory (WM) differences in TRS and non-TRS patients, and (iii) whether an alteration in the glutamate (Glu) level is associated with WM. The TRS patients had a higher glutamate + glutamine (Glx)/NAAx ratio compared to the non-TRS patients and HCs in the ACC, but this was not significantly different in the MPFC. Further research is needed to probe the value using the relationship between Glu and WM as a potential prognostic predictor of schizophrenia

Objectives

Results

Conclusion