Glutamatergic Neurometabolite Levels in Patients With Ultra-Treatment-Resistant Schizophrenia: A Cross-Sectional 3T Proton Magnetic Resonance Spectroscopy Study

Yusuke Iwata, Shinichiro Nakajima, Eric Plitman, Fernando Caravaggio, Julia Kim, Parita Shah, Wanna Mar, Sofia Chavez, Vincenzo De Luca, Masaru Mimura, Gary Remington, Philip Gerretsen, Ariel Graff-Guerrero

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22 Citations (Scopus)

Abstract

Background: In terms of antipsychotic treatment response, patients with schizophrenia can be classified into three groups: 1) treatment resistant to both non-clozapine (non-CLZ) antipsychotics and CLZ (ultra-treatment-resistant schizophrenia [URS]), 2) treatment resistant to non-CLZ antipsychotics but CLZ-responsive schizophrenia [non-URS]), and 3) responsive to first-line antipsychotics (non-treatment-resistant schizophrenia). This study aimed to compare glutamatergic neurometabolite levels among these three patient groups and healthy control subjects using proton magnetic resonance spectroscopy. Methods: Glutamate and glutamate+glutamine levels were assessed in the caudate, the dorsal anterior cingulate cortex (dACC), and the dorsolateral prefrontal cortex using 3T proton magnetic resonance spectroscopy (point-resolved spectroscopy, echo time = 35 ms). Glutamatergic neurometabolite levels were compared between the groups. Results: A total of 100 participants were included, consisting of 26 patients with URS, 27 patients with non-URS, 21 patients with non-treatment-resistant schizophrenia, and 26 healthy control subjects. Group differences were detected in ACC glutamate+glutamine levels (F3,96 = 2.93, p =.038); patients with URS showed higher dACC glutamate+glutamine levels than healthy control subjects (p =.038). There were no group differences in the caudate or dorsolateral prefrontal cortex. Conclusions: Taken together with previous studies that demonstrated higher ACC glutamate levels in patients with treatment-resistant schizophrenia, this study suggests that higher levels of ACC glutamatergic metabolites may be among the shared biological characteristics of treatment resistance to antipsychotics, including CLZ.

Original languageEnglish
JournalBiological Psychiatry
DOIs
Publication statusAccepted/In press - 2018 Jan 1

Keywords

  • H-MRS
  • Antipsychotic
  • Clozapine
  • Glutamate
  • Schizophrenia
  • Treatment-resistant

ASJC Scopus subject areas

  • Biological Psychiatry

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    Iwata, Y., Nakajima, S., Plitman, E., Caravaggio, F., Kim, J., Shah, P., Mar, W., Chavez, S., De Luca, V., Mimura, M., Remington, G., Gerretsen, P., & Graff-Guerrero, A. (Accepted/In press). Glutamatergic Neurometabolite Levels in Patients With Ultra-Treatment-Resistant Schizophrenia: A Cross-Sectional 3T Proton Magnetic Resonance Spectroscopy Study. Biological Psychiatry. https://doi.org/10.1016/j.biopsych.2018.09.009