Increased serum glutamate in depressed patients

Kim, J S; Schmid-Burgk, W.; Claus, Daniel; Kornhuber, H. H.

doi:10.1007/bf00345492

Cited by 176 publications

(72 citation statements)

References 16 publications

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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: 99%

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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Section: Glutamatergic Pathwaysmentioning

confidence: 99%

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

Lai

Scarr

Udawela

et al. 2016

WJP

137

108

View full text Add to dashboard Cite

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“…NMDA receptor antagonists increase the serotonin levels in the brain. 20,21 Several studies showed an increased activity of the glutamatergic system in the peripheral blood of depressive patients, [22][23][24] although this result could not be replicated by all authors. 25 The inconsistency of the findings, however, might be due to medication effects, low statistical power and a lack of appropriate control of diagnosis.…”

Section: Glutamate In Depressionmentioning

confidence: 99%

The immune-mediated alteration of serotonin and glutamate: towards an integrated view of depression

2007

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Beside the well-known deficiency in serotonergic neurotransmission as pathophysiological correlate of major depression (MD), recent evidence points to a pivotal role of increased glutamate receptor activation as well. However, cause and interaction of these neurotransmitter alterations are not understood. In this review, we present a hypothesis integrating current concepts of neurotransmission and hypothalamus-pituitary-adrenal (HPA) axis dysregulation with findings on immunological alterations and alterations in brain morphology in MD. An immune activation including increased production of proinflammatory cytokines has repeatedly been described in MD. Proinflammatory cytokines such as interleukin-2, interferon-c, or tumor necrosis factor-a activate the tryptophan-and serotonin-degrading enzyme indoleamine 2,3-dioxygenase (IDO). Depressive states during inflammatory somatic disorders are also associated with increased proinflammatory cytokines and increased consumption of tryptophan via activation of IDO. An enhanced consumption of serotonin and its precursor tryptophan through IDO activation could well explain the reduced availability of serotonergic neurotransmission in MD. An increased activation of IDO and its subsequent enzyme kynurenine monooxygenase by proinflammatory cytokines, moreover, leads to an enhanced production of quinolinic acid, a strong agonist of the glutamatergic N-methyl-D-aspartate receptor. In inflammatory states of the central nervous system, IDO is mainly activated in microglial cells, which preferentially metabolize tryptophan to the NMDA receptor agonist quinolinic acid, whereas astrocytes -counteracting this metabolism due to the lack of an enzyme of this metabolism -have been observed to be reduced in MD. Therefore the type 1/type 2 immune response imbalance, associated with an astrocyte/microglia imbalance, leads to serotonergic deficiency and glutamatergic overproduction. Astrocytes are further strongly involved in re-uptake and metabolic conversion of glutamate. The reduced number of astrocytes could contribute to both, a diminished counterregulation of IDO activity in microglia and an altered glutamatergic neurotransmission. Further search for antidepressant agents should take into account anti-inflammatory drugs, for example, cyclooxygenase-2 inhibitors, might exert antidepressant effects by acting on serotonergic deficiency, glutamatergic hyperfunction and antagonizing neurotoxic effects of quinolinic acid. Molecular Psychiatry (2007) 12, 988-1000; doi:10.1038/sj.mp.4002006; published online 24 April 2007 Keywords: major depression; psychoneuroimmunology; IDO; glutamate; immune system; serotonin Glutamate in depressionGlutamatergic neurotransmission is involved in depression and interacts with the serotonergic and noradrenergic systems The common therapeutic mechanism of antidepressant drugs is the enhancement of serotonergic and/or noradrenergic neurotransmission. On the basis of this pharmacological profile of antidepressant drugs, neurochemical research on major depression ...

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“…Blood glutamate levels have been shown to increase in medicated patients [61,62]. Mitani et al [63] reported that increased glutamate plasma levels reflected the severity of depression.…”

Section: Role Of Glutamatergic Transmission In Depressionmentioning

confidence: 99%

Metabotropic Glutamate Receptors: Potential Drug Targets for Psychiatric Disorders

Yasuhara¹

2010

TOMCJ

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Metabotropic glutamate receptors (mGlu receptors) have emerged as new therapeutic targets for psychiatric disorders, such as schizophrenia, depression and anxiety with their regulatory roles in glutamatergic transmissions. To date, several ligands selective for each mGlu receptor have been synthesized, and pharmacological significances of these ligands have been demonstrated in animal models. Among them, mGlu2/3 receptor agonists have been proven to be effective for treating schizophrenia and anxiety disorders in clinical studies, which may prove utilities of mGlu receptor ligands for the treatment of psychiatric disorders. This article reviews recent advances in development of each mGlu receptor ligands and their therapeutic potential.

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Increased serum glutamate in depressed patients

Cited by 176 publications

References 16 publications

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

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

The immune-mediated alteration of serotonin and glutamate: towards an integrated view of depression

Metabotropic Glutamate Receptors: Potential Drug Targets for Psychiatric Disorders

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