title: Reduced frontal glutamate + glutamine and N-acetylaspartate levels in patients with chronic schizophrenia but not in those at clinical high risk for psychosis or with first-episode schizophrenia.
abstract: Changes in brain pathology as schizophrenia progresses have been repeatedly suggested by previous studies. Meta-analyses of previous proton magnetic resonance spectroscopy ((1)H MRS) studies at each clinical stage of schizophrenia indicate that the abnormalities of N-acetylaspartate (NAA) and glutamatergic metabolites change progressively. However, to our knowledge, no single study has addressed the possible differences in (1)H MRS abnormalities in subjects at 3 different stages of disease, including those at ultrahigh risk for psychosis (UHR), with first-episode schizophrenia (FES), and with chronic schizophrenia (ChSz). In the current study, 24 patients with UHR, 19 FES, 25 ChSz, and their demographically matched 3 independent control groups (n = 26/19/28 for the UHR, FES, and ChSz control groups, respectively) underwent (1)H MRS in a 3-Tesla scanner to examine metabolites in medial prefrontal cortex. The analysis revealed significant decreases in the medial prefrontal NAA and glutamate + glutamine (Glx) levels, specifically in the ChSz group as indexed by a significant interaction between stage (UHR/FES/ChSz) and clinical status (patients/controls) (P = .008). Furthermore, the specificity of NAA and Glx reductions compared with the other metabolites in the patients with ChSz was also supported by a significant interaction between the clinical status and types of metabolites that only occurred at the ChSz stage (P = .001 for NAA, P = .004 for Glx). The present study demonstrates significant differences in (1)H MRS abnormalities at different stages of schizophrenia, which potentially correspond to changes in glutamatergic neurotransmission, plasticity, and/or excitotoxicity and regional neuronal integrity with relevance for the progression of schizophrenia.
authors.affiliation: Department of Neuropsychiatry, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan;
authors.forename: Tatsunobu
authors.initials: T
authors.lastname: Natsubori
authors.affiliation: Department of Neuropsychiatry, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan;
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Inoue
authors.affiliation: Department of Radiology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan; Department of Radiology, Nihon University School of Medicine, Tokyo, Japan;
authors.forename: Osamu
authors.initials: O
authors.lastname: Abe
authors.affiliation: Department of Neuropsychiatry, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan;
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Takano
authors.affiliation: Department of Neuropsychiatry, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan;
authors.forename: Norichika
authors.initials: N
authors.lastname: Iwashiro
authors.affiliation: Department of Neuropsychiatry, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan;
authors.forename: Yuta
authors.initials: Y
authors.lastname: Aoki
authors.affiliation: Department of Neuropsychiatry, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan;
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Koike
authors.affiliation: Department of Neuropsychiatry, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan;
authors.forename: Noriaki
authors.initials: N
authors.lastname: Yahata
authors.affiliation: Department of Radiology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan;
authors.forename: Masaki
authors.initials: M
authors.lastname: Katsura
authors.affiliation: Department of Radiology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan;
authors.forename: Wataru
authors.initials: W
authors.lastname: Gonoi
authors.affiliation: Department of Radiology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan;
authors.forename: Hiroki
authors.initials: H
authors.lastname: Sasaki
authors.affiliation: Department of Radiology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan;
authors.forename: Hidemasa
authors.initials: H
authors.lastname: Takao
authors.affiliation: Department of Neuropsychiatry, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan;
authors.forename: Kiyoto
authors.initials: K
authors.lastname: Kasai
authors.affiliation: Department of Neuropsychiatry, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan; yamasue-tky@umin.ac.jp.
authors.forename: Hidenori
authors.initials: H
authors.lastname: Yamasue
mesh_terms: D000293:Adolescent; D000328:Adult; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000378:metabolism; D002908:Chronic Disease; D018450:Disease Progression; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism*; D005973:Glutamine / Q000378:metabolism*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008875:Middle Aged; D017397:Prefrontal Cortex / Q000378:metabolism*; D062706:Prodromal Symptoms; D011618:Psychotic Disorders / Q000378:metabolism*; D012306:Risk; D012559:Schizophrenia / Q000378:metabolism*; D055815:Young Adult
chemical_list: D005973:Glutamine; D001224:Aspartic Acid; D018698:Glutamic Acid; C000179:N-acetylaspartate
keywords: anterior cingulate cortex; at-risk mental state; biomarkers; frontal lobe; magnetic resonance imaging; neurochemical abnormality
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