Anterior Cingulate Cortex Glutamate Levels Are Related to Response to Initial Antipsychotic Treatment in Drug-Naive First-Episode Schizophrenia Patients

Abstract

The glutamatergic system has previously been shown to be involved in the pathophysiology of schizophrenia and the mechanisms of action of antipsychotic treatment. The present study aimed to investigate the relationship between the levels of glutamate (Glu) or Glu/total creatine (Glu/Cr+PCr) in the anterior cingulate cortex (ACC) and psychiatric symptoms as well as the response to antipsychotic treatment. We performed proton magnetic resonance spectroscopy (1 H-MRS) to measure Glu and Glu/Cr+PCr in the ACC of 35 drug-naïve first-episode schizophrenia (FES) patients and 40 well-matched healthy controls (HCs). After scanning, we treated the patients with risperidone for eight weeks. Remission status was based on the Positive and Negative Syndrome Scale (PANSS) scores at week 8. At baseline, there were no significant differences in the levels of Glu or Glu/Cr+PCr in the ACC between drug-naïve FES patients and HCs. Lower baseline levels of Glu/Cr+PCr but not Glu in the ACC were associated with more severe negative symptoms of schizophrenia. Compared to the remission group (RM), the non-remission group (NRM) had lower baseline ACC Glu levels (P < 0.05). Our results suggest that ACC Glu levels may be related to the severity of symptoms in the early stages of schizophrenia and therefore may be a marker with which to evaluate the treatment effect of antipsychotics in schizophrenia patients.

Frontal neural metabolite changes in schizophrenia and their association with cognitive control: A systematic review

“…Both Olbrich et al (2008) and Li et al (2020) found significant negative correlation between frontal Glu levels in FEP patients, and their scores on BACS and PANNS-N respectively. This effect was not replicated by Bartolomeo et al (2019) who also failed to find a significant relationship with the mismatch negativity results.…”

“…Two studies ( Li et al, 2020 ; Olbrich et al, 2008 ) reported negative correlations between frontal Glu levels and negative symptom severity with lower Glu levels being associated with more negative symptoms. In contrast, Jauhar et al (2018) did not find a significant correlation between medial frontal Glu levels and negative symptoms, but a negative correlation between Glu and positive symptom severity, i.e.…”

“…measuring just positive or negative symptoms) and metabolite levels, but the results represented a mix of positive and negative correlations in chronic SZ patients. Negative symptoms have been shown to be associated with frontal Glx levels in chronic SZ patients (negative correlation in medial areas and a positive correlation in frontolateral areas), and with Glu levels in FEP patients (negative correlations; Li et al, 2020 ; Olbrich et al, 2008 ; but see Jauhar et al, 2018 ).…”

Increased Glutamate Plus Glutamine in the Right Middle Cingulate in Early Schizophrenia but Not in Bipolar Psychosis: A Whole Brain 1H-MRS Study

“…Consistently, antipsychotic-naïve schizophrenia patients had increased dorsal striatal glutamate, which normalized with prospective risperidone treatment ( 7 ). However, a recent study in antipsychotic-naïve schizophrenia failed to detect any differences in anterior cingulate glutamate ( 6 ). Furthermore, two 7T studies of the anterior cingulate in chronically-ill patients found glutamate reductions ( 26 , 27 ).…”

“…Schizophrenia studies using single-voxel 1 H-MRS suggest glutamate increases in "basal ganglia" (3) though more recent studies at 7T in early antipsychotic-treated psychosis found prefrontal glutamate reductions (4,5). Furthermore, nevertreated schizophrenia patients had no glutamate differences relative to healthy control subjects in dorsal anterior cingulate (6), but increases have been documented in the dorsal striatum in this population (7). Like schizophrenia, bipolar-I is a chronic, neurodevelopmental disorder, often presents with psychotic symptoms, and is commonly treated with antipsychotic medications (8).…”