Reduced d-serine to total serine ratio in the cerebrospinal fluid of drug naive schizophrenic patients
Abstract
Several lines of evidence suggest that D-serine, an endogenous agonist of the glycine site on the NMDA receptors, might play a role in the pathophysiology of schizophrenia. The purpose of this study was to determine whether levels of D- and L-serine or D-serine ratio (D-serine/total serine) in cerebrospinal fluid (CSF) were altered in first episode and drug-naive schizophrenic patients. The CSF levels of D- and L-serine in 25 male first episode and drug-naive schizophrenic patients and 17 age-matched male healthy subjects were measured using a column-switching high performance liquid chromatography system. The percentage of D-serine in the total serine of patients was significantly (z = -2.01, p = 0.044) lower than that of controls. This study suggests that synthetic or metabolic pathways of D-serine may be abnormal in the brain of drug-naive schizophrenic patients, supporting the NMDA receptor dysfunction hypothesis of schizophrenia.
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Post-mortem studies of schizophrenia brains revealed lower GRIN1 expression, increases in kynurenate, and reductions in D-serine and D-serine racemase.
“Post-mortem studies of the brain of patients with schizophrenia have revealed lower levels of expression of the obligate NMDAR subunit GRIN1 (glutamate receptor ionotropic, NMDA 1), increases in the expression of the endogenous NMDAR antagonist kynurenate, and a reduction in levels of the NMDAR co-agonist D-serine and the enzyme that catalyses its production, D-serine racemase 10,[16][17][18] .”
From Linking early-life NMDAR hypofunction and oxidative stress in schizophrenia pathogenesis (2016) · cites this paper as [17]
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Self-citation
- Authors
- Hashimoto, K., Engberg, G., Shimizu, E., Nordin, C., Lindström, L. H., & Iyo, M.
- Affiliations
- Chiba University (JP)
- Karolinska Institutet (SE)
- Linköping University Hospital (SE)
- Uppsala University (SE)
- Corresponding author
- Hashimoto, Kenji
- Venue
- Progress in Neuro-Psychopharmacology and Biological Psychiatry
- Publisher
- Elsevier BV
- Published
- 2005-06
- Volume
- 29
- Issue
- 5
- Pages
- 767-769
- ISSN
- 0278-5846 (ISSN-L)
- OpenAlex
- W2078450450
- Cited by
- 267
- References
- 13
- Citations by year
- 2026: 8 · 2025: 10 · 2024: 11 · 2023: 10 · 2022: 6 · 2021: 7 · 2020: 12 · 2019: 18 · 2018: 15 · 2017: 12 · 2016: 16 · 2015: 13 · 2014: 12 · 2013: 14 · 2012: 14
- FWCI
- 8.86
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Progress in Neuro-Psychopharmacology and Biological Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Keywords
- D-serine, L-serine, cerebrospinal fluid, schizophrenia, first-episode schizophrenia, drug-naive patients, NMDA receptor, serine metabolism
- MeSH terms
- Adolescent, Adult, Chromatography, High Pressure Liquid, Humans, Male, Schizophrenia, Serine, Stereoisomerism, Receptors, N-Methyl-D-Aspartate
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