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

Jinguang Li,Chunwang Li,Dong Wang,Hongying Han,Honghong Ren,Jinsong Tang,Lijun Ouyang,Jun Zhou,Liu Yuan,Xiaogang Chen,Zongchang Li,Ying He,Xiaoqian Ma

doi:10.3389/fpsyt.2020.553269

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 (1H–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.

Highlights

Schizophrenia is a complex and severe mental disorder with a lifetime prevalence of 1% worldwide [1]
First-episode schizophrenia studies have shown that approximately one-quarter of firstepisode schizophrenia (FES) patients have persistent psychosis symptoms despite adequate initial treatment [14], and this finding, together with the glutamatergic hypothesis, may suggest that dopaminergic drugs are ineffective throughout illness in the subgroup of schizophrenia patients, who have an inadequate response to initial treatment with dopaminergic drugs
Previous studies have observed that phencyclidine (PCP) and ketamine, which are antagonists of N-methyl-d-aspartate glutamate receptor (NMDAR), can transiently induce positive psychotic symptoms, such as delusions, hallucinations, agitation, and catatonic behavior, and negative psychotic symptoms including blunted affect, anhedonia, avolition, and inattention [6, 33]

Summary

Introduction

Schizophrenia is a complex and severe mental disorder with a lifetime prevalence of 1% worldwide [1] It has been over 60 years since the first antipsychotic, chlorpromazine, was initially developed, a third of patients with schizophrenia have a suboptimal response to firstline antipsychotic treatment, most of which mainly target dopamine D2 receptors [2, 3]. In pharmacological animal models of schizophrenia, compared with other drugs, such as amphetamine, NMDAR antagonists can cause positive and negative symptoms that more closely mimic those of schizophrenia [12]. First-episode schizophrenia studies have shown that approximately one-quarter of firstepisode schizophrenia (FES) patients have persistent psychosis symptoms despite adequate initial treatment [14], and this finding, together with the glutamatergic hypothesis, may suggest that dopaminergic drugs are ineffective throughout illness in the subgroup of schizophrenia patients, who have an inadequate response to initial treatment with dopaminergic drugs

Methods

Results

Conclusion