Changes in Brain Glutamate on Switching to Clozapine in Treatment-Resistant Schizophrenia

Schizophr Bull. 2021 Apr 29;47(3):662-671. doi: 10.1093/schbul/sbaa156.

Abstract

It has been suggested that the antipsychotic clozapine may modulate brain glutamate, and that this effect could contribute to its efficacy in treatment-resistant schizophrenia (TRS). The aim of this study was to examine the effects of clozapine on brain glutamate in TRS longitudinally. This study examined individuals with TRS before and 12 weeks after switching from a non-clozapine antipsychotic to treatment with clozapine as part of their normal clinical care. Proton magnetic resonance spectroscopy (1H-MRS) measured concentrations, corrected for voxel tissue content, of glutamate (Glucorr), and glutamate plus glutamine (Glxcorr) in the anterior cingulate cortex (ACC) and right caudate nucleus. Symptoms were monitored using the Positive and Negative Syndrome Scale (PANSS). Of 37 recruited patients (27 men, 39.30 years old, 84% clozapine naïve), 25 completed 1H-MRS at both timepoints. 12 weeks of clozapine was associated with a longitudinal reduction in Glucorr in the caudate (n = 23, F = 7.61 P = .01) but not in the ACC (n = 24, F = 0.02, P = .59). Percentage reduction in caudate Glucorr was positively correlated with percentage improvement in symptoms (total PANSS score, n = 23, r = .42, P = .04). These findings indicate that reductions in glutamate in the caudate nucleus may contribute to symptomatic improvement during the first months of clozapine treatment.

Keywords: 1H-MRS; anterior cingulate cortex; antipsychotic; caudate; magnetic resonance spectroscopy; psychosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antipsychotic Agents / administration & dosage
  • Antipsychotic Agents / pharmacology*
  • Caudate Nucleus* / diagnostic imaging
  • Caudate Nucleus* / metabolism
  • Clozapine / administration & dosage
  • Clozapine / pharmacology*
  • Female
  • Glutamic Acid* / drug effects
  • Glutamic Acid* / metabolism
  • Glutamine / drug effects
  • Glutamine / metabolism
  • Gyrus Cinguli* / diagnostic imaging
  • Gyrus Cinguli* / metabolism
  • Humans
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Outcome Assessment, Health Care*
  • Proton Magnetic Resonance Spectroscopy
  • Schizophrenia* / diagnostic imaging
  • Schizophrenia* / drug therapy
  • Schizophrenia* / metabolism
  • Schizophrenia* / physiopathology

Substances

  • Antipsychotic Agents
  • Glutamine
  • Glutamic Acid
  • Clozapine