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

Abstract

BackgroundAccumulating 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). MethodsThe 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. ResultsSignificantly 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. ConclusionsOur 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.