Hippocampal glutamate metabolites and glial activation in clinical high risk and first episode psychosis

Neuropsychopharmacology. 2018 Oct;43(11):2249-2255. doi: 10.1038/s41386-018-0163-0. Epub 2018 Jul 28.

Abstract

Alterations in glutamate neurotransmission have been implicated in the pathophysiology of schizophrenia, as well as in symptom severity and cognitive deficits. The hippocampus, in particular, is a site of key functional and structural abnormalities in schizophrenia. Yet few studies have investigated hippocampal glutamate in antipsychotic-naïve first episode psychosis patients or in individuals at clinical high risk (CHR) of developing psychosis. Using proton magnetic resonance spectroscopy (1H-MRS), we investigated glutamate metabolite levels in the left hippocampus of 25 CHR (19 antipsychotic-naïve), 16 patients with first-episode psychosis (13 antipsychotic-naïve) and 31 healthy volunteers. We also explored associations between hippocampal glutamate metabolites and glial activation, as indexed by [18F]FEPPA positron emission tomography (PET); symptom severity; and cognitive function. Groups differed significantly in glutamate plus glutamine (Glx) levels (F(2, 69) = 6.39, p = 0.003). Post-hoc analysis revealed that CHR had significantly lower Glx levels than both healthy volunteers (p = 0.003) and first-episode psychosis patients (p = 0.050). No associations were found between glutamate metabolites and glial activation. Our findings suggest that glutamate metabolites are altered in CHR.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cohort Studies
  • Female
  • Glutamic Acid / metabolism*
  • Hippocampus / diagnostic imaging*
  • Hippocampus / metabolism*
  • Humans
  • Male
  • Neuroglia / metabolism*
  • Positron-Emission Tomography / methods
  • Proton Magnetic Resonance Spectroscopy / methods
  • Psychotic Disorders / diagnostic imaging*
  • Psychotic Disorders / metabolism*
  • Psychotic Disorders / psychology
  • Risk Factors
  • Young Adult

Substances

  • Glutamic Acid