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

Song, Jiali; Viggiano, Andrea; Monda, Marcellino; Luca, Vincenzo De

doi:10.1159/000364828

Cited by 22 publications

(21 citation statements)

References 35 publications

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“…The result is compatible with previous reports, which showed increased serum levels of glutamate in chronic schizophrenia patients 28, 29 . A couple of reports have attempted and failed to replicate these findings 30, 31 ; however, a recent meta-analysis confirmed that the peripheral glutamate level of schizophrenia subjects was significantly higher than that of HC 24 . While these are findings pertain to chronic schizophrenia, we found increased glutamate levels in FEP.…”

Section: Discussionmentioning

confidence: 99%

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Reduced Mismatch Negativity is Associated with Increased Plasma Level of Glutamate in First-episode Psychosis

Nagai¹,

Kirihara

Tada

et al. 2017

Sci Rep

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Reduced amplitude of mismatch negativity (MMN) is one of the more promising biological markers of schizophrenia. This finding holds true in both early and chronic phases of the disorder, and is compatible with the glutamatergic dysfunction hypothesis. To further establish MMN as a biomarker of aberrant glutamatergic neurotransmission, an exploration for an association with blood levels of glutamatergic amino acids is an important next step. Despite a large body of work investigating MMN in schizophrenia, no previous studies have undertaken this endeavor. Nineteen patients with first-episode psychosis (FEP), 21 ultra-high risk individuals (UHR), and 16 healthy controls (HC) participated in the study. The MMNs in response to duration change (dMMN) and frequency change (fMMN) were measured. The fasting plasma levels of glutamate, glutamine, glycine, D-serine, and L-serine were measured. dMMN amplitudes were significantly reduced in FEP and UHR, compared to HC. The plasma levels of glutamate of FEP were significantly higher than those of HC. Higher plasma levels of glutamate were associated with smaller dMMN amplitudes in the FEP and HC groups. These findings are compatible with the hypothesis that MMN is a useful biological marker of aberrant glutamatergic neurotransmission in the early stages of schizophrenia.

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Section: Discussionmentioning

confidence: 99%

“…Peripheral glutamatergic amino acids have been investigated in patients with schizophrenia 23, 24 and a meta-analysis showed that peripheral glutamate levels in schizophrenia patients were significantly higher than those in controls 24 . This is consistent with a prevalent model of hyperglutamatergic state in schizophrenia.…”

Section: Introductionmentioning

confidence: 99%

Reduced Mismatch Negativity is Associated with Increased Plasma Level of Glutamate in First-episode Psychosis

Nagai¹,

Kirihara

Tada

et al. 2017

Sci Rep

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“…Most studies focused on peripheral glutamate levels in people with Sz. In a metaanalysis [86] of 10 studies, higher levels (standardized mean difference = 0.64; 95%CI = 0.21-1.06) of glutamate have been reported in blood from people with Sz compared to controls, however, similar dysregulations have been reported in the small number of studies that focused on major depressive disorder [90,91] , suggesting the alteration of glutamate levels is not specific to the diagnosis of Sz. Interestingly, the response of platelet intracellular calcium to glutamate was greater in people with Sz than in controls, suggesting NMDA receptor may be more sensitive in these people [87] .…”

Section: Glutamatergic Pathwaysmentioning

confidence: 96%

Biomarkers in schizophrenia: A focus on blood based diagnostics and theranostics

Lai

Scarr

Udawela

et al. 2016

WJP

137

108

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Identifying biomarkers that can be used as diagnostics or predictors of treatment response (theranostics) in people with schizophrenia (Sz) will be an important step towards being able to provide personalized treatment. Findings from the studies in brain tissue have not yet been translated into biomarkers that are practical in clinical use because brain biopsies are not acceptable and neuroimaging techniques are expensive and the results are inconclusive. Thus, in recent years, there has been search for blood-based biomarkers for Sz as a valid alternative. Although there are some encouraging preliminary data to support the notion of peripheral biomarkers for Sz, it must be acknowledged that Sz is a complex and heterogeneous disorder which needs to be further dissected into subtype using biological based and clinical markers. The scope of this review is to critically examine published blood-based biomarker of Sz, focusing on possible uses for diagnosis, treatment response, or their relationship with schizophreniaassociated phenotype. We sorted the studies into six categories which include: (1) brain-derived neurotrophic factor; (2) inflammation and immune function; (3) neurochemistry; (4) oxidative stress response and metabolism; (5) epigenetics and microRNA; and (6) transcriptome and proteome studies. This review also summarized the molecules which have been conclusively reported as potential blood-based biomarkers for Sz in different blood cell types. Finally, we further discusses the pitfall of current blood-based studies and suggest that a prediction model-based, Sz specific, blood World Journal of Psychiatry W J P oriented study design as well as standardize blood collection conditions would be useful for Sz biomarker development.

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“…10). According to this model, the fact that some carriers are susceptible to meningococcal diseases while others are not might be partly explained by variations in the glutamate concentrations in the blood, which are affected by many factors (45,(50)(51)(52). However, reduction of the glutamate concentrations beneath meningococcal colonies on HBMEC could not be directly proven, and further examinations should be performed when an in vivo molecular probe for glutamate becomes available.…”

Section: Discussionmentioning

confidence: 99%

Multiple Functions of Glutamate Uptake via Meningococcal GltT-GltM l -Glutamate ABC Transporter in Neisseria meningitidis Internalization into Human Brain Microvascular Endothelial Cells

Takahashi

Yanagisawa²,

Kim

et al. 2015

Infect Immun

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cWe previously reported that Neisseria meningitidis internalization into human brain microvasocular endothelial cells (HBMEC) was triggered by the influx of extracellular L-glutamate via the GltT-GltM L-glutamate ABC transporter, but the underlying mechanism remained unclear. We found that the ⌬gltT ⌬gltM invasion defect in assay medium (AM) was alleviated in AM without 10% fetal bovine serum (FBS) [AM(؊S)]. The alleviation disappeared again in AM(؊S) supplemented with 500 M glutamate. Glutamate uptake by the ⌬gltT ⌬gltM mutant was less efficient than that by the wild-type strain, but only upon HBMEC infection. We also observed that both GltT-GltM-dependent invasion and accumulation of ezrin, a key membrane-cytoskeleton linker, were more pronounced when N. meningitidis formed larger colonies on HBMEC under physiological glutamate conditions. These results suggested that GltT-GltM-dependent meningococcal internalization into HBMEC might be induced by the reduced environmental glutamate concentration upon infection. Furthermore, we found that the amount of glutathione within the ⌬gltT ⌬gltM mutant was much lower than that within the wild-type N. meningitidis strain only upon HBMEC infection and was correlated with intracellular survival. Considering that the L-glutamate obtained via GltT-GltM is utilized as a nutrient in host cells, L-glutamate uptake via GltT-GltM plays multiple roles in N. meningitidis internalization into HBMEC. N eisseria meningitidis is a Gram-negative microorganism and an exclusive human pathogen. It usually exists in an asymptomatic nasopharyngeal carriage state at a rate of 0.4% to 25% in human populations (1, 2). However, N. meningitidis can cause devastating invasive diseases, such as septicemia or meningitis, by penetration of the mucosal tissue, invasion of the bloodstream, and colonization of the meninges. Human genome-wide association studies (3, 4) identified single nucleotide polymorphisms in complement factor H (CFH) and CFH-related protein 3 (CFHR3), and CFHR3 promotes immune activation by acting as an antagonist of CFH (5). Environmental conditions, such as smoking (6, 7) and climate (8), are also likely to be important in determining the outcome of infection. However, the exact reasons why the diseases occur in some individuals and not in others remain unclear.Many attempts to identify bona fide virulence factors in N. meningitidis have been reported. Surface molecules, such as Opa, Opc, pili, lipooligosaccharide, and the polysaccharide capsule, have been identified as adhesive and invasive factors in N. meningitidis (9-12). In addition, genome informatics also revealed several minor adhesion and invasion proteins, such as App (13), NhhA (14), MspA (15), and NadA (16). Other attempts to find meningococcal virulence factors by genome informatics involved comparisons between commensal and pathogenic bacteria (17) and the modes of bacterial virulence evolution (18). However, many of the so-called meningococcal "virulence genes" are also present in commensal neisserial species (19,...

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

Cited by 22 publications

References 35 publications

Reduced Mismatch Negativity is Associated with Increased Plasma Level of Glutamate in First-episode Psychosis

Reduced Mismatch Negativity is Associated with Increased Plasma Level of Glutamate in First-episode Psychosis

Biomarkers in schizophrenia: A focus on blood based diagnostics and theranostics

Multiple Functions of Glutamate Uptake via Meningococcal GltT-GltM l -Glutamate ABC Transporter in Neisseria meningitidis Internalization into Human Brain Microvascular Endothelial Cells

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