Journal
SCHIZOPHRENIA BULLETIN
Volume 40, Issue 5, Pages 1128-1139Publisher
OXFORD UNIV PRESS
DOI: 10.1093/schbul/sbt124
Keywords
anterior cingulate cortex; at-risk mental state; biomarkers; frontal lobe; magnetic resonance imaging; neurochemical abnormality
Categories
Funding
- Ministry of Education, Culture, Sports, Science and Technology (MEXT)
- KAKENHI [22689034, 20591378, 21249064]
- Global Center of Excellence (COE) Program Comprehensive Center of Education and Research for Chemical Biology of the Diseases
- Health and Labour Sciences Research Grants for Comprehensive Research on Disability, Health and Welfare [H22-seishin-ippan-015]
- Grants-in-Aid for Scientific Research [22689034, 20591378] Funding Source: KAKEN
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Changes in brain pathology as schizophrenia progresses have been repeatedly suggested by previous studies. Meta-analyses of previous proton magnetic resonance spectroscopy (H-1 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 1H 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 1H 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 1H 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.
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