Serine and other amino acids that function as coagonists at the N-methyl-d-aspartate receptor (NMDAR) have been extensively investigated in schizophrenia (SCZ). However, studies comparing amino acid levels in body fluids of SCZ patients with healthy controls have yielded inconsistent results. We therefore conducted a meta-analysis (search: May 9, 2013) of serine, l-serine, d-serine, glycine, alanine, proline, and aspartate levels in blood and cerebrospinal fluid (CSF) obtained from adult SCZ patients and healthy controls. Standardized differences of means (SDMs) were computed, and heterogeneity, subgroup, sensitivity, and publication bias analyses were conducted. Blood serine levels were found to be significantly higher in SCZ patients compared to healthy controls (SDM=0.280 (0.021-0.540), p=0.034; N=1671 subjects), whereas CSF serine, l-serine, d-serine, glycine, alanine, proline, and aspartate levels did not differ. Stratification by sex suggested that the case-control difference in blood serine levels particularly applies to male subjects. These results provide support for blood serine level aberrations in SCZ patients and warrant further research to disentangle the involvement of serine with SCZ in both sexes.
Studies of the inter-relationship between cerebrospinal fluid and plasma amino acid concentrations in normal individuals
High concentrations of neutral amino acids activate NMDA receptor currents in rat hippocampal neurons
Serum amino acids, central monoamines, and hormones in drug-naive, drug-free, and neuroleptic-treated schizophrenic patients and healthy subjects
Plasma amino acids in relation to cerebrospinal fluid monoamine metabolites in schizophrenic patients and healthy controls
Serine and folate metabolism in fibroblasts from episodic psychotic patients with psychedelic symptoms
Increased concentrations of various amino acids in schizophrenic patients. Evidence for heterozygosity effects?
Amino acids in plasma and CSF and monoamine metabolites in CSF: interrelationship in healthy subjects
Impaired glycine-serine conversion and increased plasma taurine levels in episodic psychotic patients with psychedelic symptoms
D-serine, an endogenous synaptic modulator: localization to astrocytes and glutamate-stimulated release
Preliminary investigation of high-dose oral glycine on serum levels and negative symptoms in schizophrenia: an open-label trial
The neuropsychopharmacology of phencyclidine: from NMDA receptor hypofunction to the dopamine hypothesis of schizophrenia
Modulation by L- and D-isoforms of amino acids of the L-glutamate response of N-methyl-D-aspartate receptors
NMDA agonists and antagonists as probes of glutamatergic dysfunction and pharmacotherapies in neuropsychiatric disorders
Serine racemase: a glial enzyme synthesizing D-serine to regulate glutamate-N-methyl-D-aspartate neurotransmission
Decreased serum levels of D-serine in patients with schizophrenia: evidence in support of the N-methyl-D-aspartate receptor hypofunction hypothesis of schizophrenia
Plasma glycine and serine levels in schizophrenia compared to normal controls and major depression: relation to negative symptoms
Amino acids in schizophrenia: evidence for lower tryptophan availability during treatment with atypical antipsychotics?
D-serine efficacy as add-on pharmacotherapy to risperidone and olanzapine for treatment-refractory schizophrenia
Reduced D-serine to total serine ratio in the cerebrospinal fluid of drug naive schizophrenic patients
Identification of multiple serine racemase (SRR) mRNA isoforms and genetic analyses of SRR and DAO in schizophrenia and D-serine levels
Relation of plasma glycine, serine, and homocysteine levels to schizophrenia symptoms and medication type
Analysis of correlation between serum D-serine levels and functional promoter polymorphisms of GRIN2A and GRIN2B genes
Preliminary evidence for a link between schizophrenia and NMDA-glycine site receptor ligand metabolic enzymes, d-amino acid oxidase (DAAO) and kynurenine aminotransferase-1 (KAT-1)
High glycine levels are associated with prepulse inhibition deficits in chronic schizophrenia patients
d-Amino acid oxidase and serine racemase in human brain: normal distribution and altered expression in schizophrenia.
Cerebrospinal fluid D-serine and glycine concentrations are unaltered and unaffected by olanzapine therapy in male schizophrenic patients
Expression of D-serine and glycine transporters in the prefrontal cortex and cerebellum in schizophrenia
Two mass-spectrometric techniques for quantifying serine enantiomers and glycine in cerebrospinal fluid: potential confounders and age-dependent ranges
Changes in plasma glycine, L-serine, and D-serine levels in patients with schizophrenia as their clinical symptoms improve: results from the Juntendo University Schizophrenia Projects (JUSP)
Association analysis of glycine- and serine-related genes in a Japanese population of patients with schizophrenia
In vivo detection of serine in the human brain by proton magnetic resonance spectroscopy (1H-MRS) at 7 Tesla
Potential pathophysiological role of D-amino acid oxidase in schizophrenia: immunohistochemical and in situ hybridization study of the expression in human and rat brain
The involvement of the NMDA receptor D-serine/glycine site in the pathophysiology and treatment of schizophrenia
Measurement of glycine in human prefrontal brain by point-resolved spectroscopy at 7.0 tesla in vivo
Increased D-amino acid oxidase expression in the bilateral hippocampal CA4 of schizophrenic patients: a post-mortem study.
Plasma alanine levels increase in patients with schizophrenia as their clinical symptoms improve-Results from the Juntendo University Schizophrenia Projects (JUSP)
Significance of NMDA receptor-related glutamatergic amino acid levels in peripheral blood of patients with schizophrenia
From revolution to evolution: the glutamate hypothesis of schizophrenia and its implication for treatment
Metabolomic analysis of biochemical changes in the plasma and urine of first-episode neuroleptic-naïve schizophrenia patients after treatment with risperidone
Measurement of nitric oxide-related amino acids in serum and plasma: effects of blood clotting and type of anticoagulant
Changes in plasma D-serine, L-serine, and glycine levels in treatment-resistant schizophrenia before and after clozapine treatment
Phosphoserine phosphatase activity is elevated and correlates negatively with plasma d-serine concentration in patients with schizophrenia
d-amino acid oxidase knockout (Dao(-/-) ) mice show enhanced short-term memory performance and heightened anxiety, but no sleep or circadian rhythm disruption
Role for neonatal D-serine signaling: prevention of physiological and behavioral deficits in adult Pick1 knockout mice
In vivo assessment of neurotransmitters and modulators with magnetic resonance spectroscopy: application to schizophrenia
Markers of glutamate signaling in cerebrospinal fluid and serum from patients with bipolar disorder and healthy controls
Multi-regression analysis revealed a relationship between l-serine and methionine, a component of one-carbon metabolism, in the normal control but not in the schizophrenia
The DRD2 rs1076560 polymorphism and schizophrenia-related intermediate phenotypes: A systematic review and meta-analysis
SlgA, encoded by the homolog of the human schizophrenia-associated gene PRODH , acts in clock neurons to regulate Drosophila aggression
Comparative Pro-cognitive and Neurochemical Profiles of Glycine Modulatory Site Agonists and Glycine Reuptake Inhibitors in the Rat: Potential Relevance to Cognitive Dysfunction and Its Management.
Reduced Mismatch Negativity is Associated with Increased Plasma Level of Glutamate in First-episode Psychosis
Dysregulation of kynurenine pathway and potential dynamic changes of kynurenine in schizophrenia: A systematic review and meta-analysis.
In Vivo Brain Glycine and Glutamate Concentrations in Patients With First-Episode Psychosis Measured by Echo Time-Averaged Proton Magnetic Resonance Spectroscopy at 4T
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