Early treatment response in first episode psychosis: a 7-T magnetic resonance spectroscopic study of glutathione and glutamate

Mol Psychiatry. 2020 Aug;25(8):1640-1650. doi: 10.1038/s41380-020-0704-x. Epub 2020 Mar 24.

Abstract

Early response to antipsychotic medications is one of the most important determinants of later symptomatic and functional outcomes in psychosis. Glutathione and glutamate have emerged as promising therapeutic targets for patients demonstrating inadequate response to dopamine-blocking antipsychotics. Nevertheless, the role of these neurochemicals in the mechanism of early antipsychotic response remains poorly understood. Using a longitudinal design and ultrahigh field 7-T magnetic resonance spectroscopy (MRS) protocol in 53 subjects, we report the association between dorsal anterior cingulate cortex glutamate and glutathione, with time to treatment response in drug naive (34.6% of the sample) or minimally medicated first episode patients with schizophreniform disorder, schizophrenia, and schizoaffective disorder. Time to response was defined as the number of weeks required to reach a 50% reduction in the PANSS-8 scores. Higher glutathione was associated with shorter time to response (F = 4.86, P = 0.017), while higher glutamate was associated with more severe functional impairment (F = 5.33, P = 0.008). There were no significant differences between patients and controls on measures of glutamate or glutathione. For the first time, we have demonstrated an association between higher glutathione and favorable prognosis in FEP. We propose that interventions that increase brain glutathione levels may improve outcomes of early intervention in psychosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antipsychotic Agents / pharmacology
  • Antipsychotic Agents / therapeutic use*
  • Female
  • Glutamic Acid / analysis
  • Glutamic Acid / metabolism*
  • Glutathione / analysis
  • Glutathione / metabolism*
  • Gyrus Cinguli / drug effects
  • Gyrus Cinguli / metabolism
  • Humans
  • Longitudinal Studies
  • Magnetic Resonance Spectroscopy
  • Male
  • Prognosis
  • Psychotic Disorders / diagnosis
  • Psychotic Disorders / diagnostic imaging*
  • Psychotic Disorders / drug therapy*
  • Psychotic Disorders / metabolism
  • Schizophrenia / diagnostic imaging
  • Schizophrenia / drug therapy
  • Schizophrenia / metabolism
  • Time Factors
  • Young Adult

Substances

  • Antipsychotic Agents
  • Glutamic Acid
  • Glutathione

Grants and funding