Increased plasma glutamate by antipsychotic medication and its relationship to glutaminase 1 and 2 genotypes in schizophrenia — Juntendo University Schizophrenia Projects (JUSP)

Maeshima, Hitoshi; Ohnuma, Tohru; Sakai, Yoshie; Shibata, Nobuto; Baba, Hajime; Ihara, Hiroshi; Higashi, Maiko; Ohkubo, Taku; Nozawa, Eiko; Abe, S.; Ichikawa, Aya; Nakano, Yoshitaka; Utsumi, Yushi; Suzuki, Tomohiko; Arai, Heii

doi:10.1016/j.pnpbp.2007.06.009

Cited by 31 publications

(23 citation statements)

References 45 publications

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“…A total of 20 studies on peripheral glutamate levels in schizophrenia were identified. Of these, three studies were excluded because healthy controls were not included in the study design [13,14,20], three studies were excluded because mean glutamate levels were not reported [14,21,22] and a further three studies were excluded because measurements were taken from the CSF rather than the blood [8,15,23]. In addition, one study was excluded because the full text of the paper could not be accessed [24].…”

Section: Resultsmentioning

confidence: 99%

“…Recent research attempting to develop novel medications has turned to glutamatergic signaling pathways to find effective treatments for all three symptom clusters [10]. Furthermore, studies have suggested that blood glutamate concentrations may be connected with the clinical course of schizophrenia [11,12,13]. It has been reported that switching from conventional neuroleptics to clozapine or olanzapine significantly increased peripheral glutamate concentrations in patients [14,15].…”

Section: Introductionmentioning

confidence: 99%

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Peripheral Glutamate Levels in Schizophrenia: Evidence from a Meta-Analysis

Song¹,

Viggiano

Monda

et al. 2014

Neuropsychobiology

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Background: Recent research attempting to develop novel medications has turned to glutamatergic signaling pathways to find effective treatments for symptom clusters of schizophrenia. This meta-analysis was undertaken to clarify whether a difference in peripheral glutamate levels exists between patients with schizophrenia and healthy controls. Methods: The electronic databases Ovid MEDLINE, PubMed, and PsycINFO were systematically searched up to April 2013. The search was limited to case-control studies of blood glutamate levels in schizophrenia written in English. The differences in glutamate levels were evaluated by calculating standardized mean differences (SMD). Results: We found ten studies that met the inclusion criteria for a total of 320 schizophrenia patients and 294 controls. The meta-analysis showed that peripheral glutamate levels in schizophrenia patients were significantly higher overall than in controls (SMD = 0.635, p = 0.004). However, a significant effect of the method used to measure glutamate concentrations was found (F = 7.36, p = 0.01) where fluorometric assay was associated with effect sizes in the opposite direction. Conclusion: A higher blood glutamate concentration was found in patients with schizophrenia. However, given the small sample size and methodological differences among studies, this result is not conclusive. More comprehensive research is needed to understand the relationship between glutamate levels in schizophrenia in the blood and the brain.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Peripheral Glutamate Levels in Schizophrenia: Evidence from a Meta-Analysis

Song¹,

Viggiano

Monda

et al. 2014

Neuropsychobiology

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“…Numerous studies have hypothesized altered activity of the glutamatergic system in schizophrenia. 50, 51, 52 However, glutamate levels measured in peripheral blood samples from patients with schizophrenia have been inconsistent across studies, in that some studies have reported increased levels, 5,7,53 nonsignificant changes 51,54 or decreased levels. 4,55,56 Longitudinal studies have shown that blood glutamate levels increase during the clinical course of antipsychotics medication and clinical improvement.…”

Section: Discussionmentioning

confidence: 99%

A snapshot of plasma metabolites in first-episode schizophrenia: a capillary electrophoresis time-of-flight mass spectrometry study

et al. 2014

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Few biomarkers have been known that can easily measure clinical conditions in mental illnesses such as schizophrenia. Capillary electrophoresis time-of-flight mass spectrometry (CE-TOFMS) is a new method that can measure ionized and low-molecular-weight metabolites. To explore global metabolomic alterations that characterize the onset of schizophrenia and identify biomarkers, we profiled the relative and absolute concentrations of the plasma metabolites from 30 patients with first-episode schizophrenia (FESZ, four drug-naïve samples), 38 healthy controls and 15 individuals with autism spectrum disorders using CE-TOFMS. Five metabolites had robust changes (increased creatine and decreased betaine, nonanoic acid, benzoic acid and perillic acid) in two independent sample sets. Altered levels of these metabolites are consistent with well-known hypotheses regarding abnormalities of the homocysteine metabolism, creatine kinase-emia and oxidative stress. Although it should be considered that most patients with FESZ received medication, these metabolites are candidate biomarkers to improve the determination of diagnosis, severity and clinical stages, especially for FESZ.

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“…The mGluR2/3 agonist LY2140023 is currently being evaluated as an antipsychotic drug in clinical trials (106). A genetic association between GA genes (Gls and Gls2) and schizophrenia has not been found (107); hence, GA is unlikely to be a causal factor for this neurological disorder, although typical antipsychotics can cause decreases in GA activity (108). Another appealing approach to reduce presynaptic glutamatergic transmission targets GA for antipsychotic drug research (109).…”

Section: Involvement Of Ga In Brain Pathological Statesmentioning

confidence: 99%

Brain glutaminases

Márquez

Martín-Rufián

Segura

et al. 2010

BioMolecular Concepts

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Glutaminase is considered as the main glutamate producer enzyme in brain. Consequently, the enzyme is essential for both glutamatergic and gabaergic transmissions. Glutaminederived glutamate and ammonia, the products of glutaminase reaction, fulfill crucial roles in energy metabolism and in the biosynthesis of basic metabolites, such as GABA, proteins and glutathione. However, glutamate and ammonia are also hazardous compounds and danger lurks in their generation beyond normal physiological thresholds; hence, glutaminase activity must be carefully regulated in the mammalian brain. The differential distribution and regulation of glutaminase are key factors to modulate the metabolism of glutamate and glutamine in brain. The discovery of novel isoenzymes, protein interacting partners and subcellular localizations indicate new functions for brain glutaminase. In this short review, we summarize recent findings that point consistently towards glutaminase as a multifaceted protein able to perform different tasks. Finally, we will highlight the involvement of glutaminase in pathological states and its consideration as a potential therapeutic target.

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Increased plasma glutamate by antipsychotic medication and its relationship to glutaminase 1 and 2 genotypes in schizophrenia — Juntendo University Schizophrenia Projects (JUSP)

Cited by 31 publications

References 45 publications

Peripheral Glutamate Levels in Schizophrenia: Evidence from a Meta-Analysis

Peripheral Glutamate Levels in Schizophrenia: Evidence from a Meta-Analysis

A snapshot of plasma metabolites in first-episode schizophrenia: a capillary electrophoresis time-of-flight mass spectrometry study

Brain glutaminases

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