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In Vivo Brain Glycine and Glutamate Concentrations in Patients With First-Episode Psychosis Measured by Echo Time–Averaged Proton Magnetic Resonance Spectroscopy at 4T

Published:September 07, 2017DOI:https://doi.org/10.1016/j.biopsych.2017.08.022

      Abstract

      Background

      Accumulating evidence suggests the involvement of abnormal glutamateric neurotransmission and N-methyl-D-aspartate receptor hypofunction in the pathophysiology of psychotic disorders. The purpose of this study was to quantify in vivo glutamate (Glu) and glycine (Gly) levels in patients with first-episode psychosis as well as age-matched healthy control subjects with magnetic resonance spectroscopy (MRS).

      Methods

      The subjects were 46 patients with first-episode psychosis (20 with a schizophrenia spectrum disorder, 26 with bipolar disorder) and 50 age-matched healthy control subjects. Glu and Gly levels were measured in vivo in the anterior cingulate cortex and posterior cingulate cortex of the subjects by using the echo time–averaged proton MRS technique at 4T (i.e., modified point resolved spectroscopy sequence: 24 echo time steps with 20-ms increments). Metabolite levels were quantified using LCModel with simulated basis sets.

      Results

      Significantly higher Glu and Gly levels were found in both the anterior cingulate cortex and posterior cingulate cortex of patients with first-episode psychosis as compared with healthy control subjects. Glu and Gly levels were positively correlated in patients. Patients with a schizophrenia spectrum disorder and bipolar disorder showed similar abnormalities.

      Conclusions

      Our findings demonstrate abnormally elevated brain Glu and Gly levels in patients with first-episode psychosis by means of echo time–averaged proton MRS at 4T. The findings implicate dysfunction of N-methyl-D-aspartate receptor and glutamatergic neurotransmission in the pathophysiology of the acute early phase of psychotic illnesses.

      Keywords

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      Linked Article

      • Excitatory Amino Acids in Schizophrenia: Both What You Have, and What You Do With Them
        Biological PsychiatryVol. 83Issue 6
        • Preview
          Excitatory amino acid (EAA) neurotransmitters, including glutamate, glycine, and D-serine, have been strongly implicated in the pathophysiology of schizophrenia. As pointed out by Kim et al. (1), symptoms of schizophrenia in general resemble the pattern associated with reduced activity of N-methyl-D-aspartate receptors (NMDARs). The basis for the reduction at present is unknown and may involve causes as a diverse as reduced integrity of pre- and postsynaptic glutamate terminals, reduced neurotransmitter concentrations, or increased concentration of endogenous antagonists (2).
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