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

• Published in: Schizophrenia bulletin 2014-09, Vol.40 (5), p.1128-1139
• Main Authors: NATSUBORI, Tatsunobu, INOUE, Hideyuki, SASAKI, Hiroki, TAKAO, Hidemasa, KASAI, Kiyoto, YAMASUE, Hidenori, ABE, Osamu, TAKANO, Yosuke, IWASHIRO, Norichika, AOKI, Yuta, KOIKE, Shinsuke, YAHATA, Noriaki, KATSURA, Masaki, GONOI, Wataru
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Adult and adolescent clinical studies; Aspartic Acid - analogs & derivatives; Aspartic Acid - metabolism; Biological and medical sciences; Chronic Disease; Disease Progression; Female; Glutamic Acid - metabolism; Glutamine - metabolism; Humans; Magnetic Resonance Spectroscopy; Male; Medical sciences; Middle Aged; Prefrontal Cortex - metabolism; Prodromal Symptoms; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Psychoses; Psychotic Disorders - metabolism; Regular; Risk; Schizophrenia; Schizophrenia - metabolism; Young Adult
• ISSN: 0586-7614; 1745-1701
• DOI: 10.1093/schbul/sbt124

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.