Elevated peripheral blood glutamate levels in major depressive disorder

Inoshita, Masatoshi; Umehara, Hiroki; Watanabe, Shinya; Nakataki, Masahito; Kinoshita, Makoto; Tomioka, Yukiko; Tajima, Atsushi; Numata, Shusuke; Ohmori, Tetsuro

doi:10.2147/ndt.s159855

Cited by 49 publications

(36 citation statements)

References 37 publications

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“…Recently, changes in the glutamate system were shown to play a significant role in the evolution of mood disorders 47 . Specifically, abnormal levels of glutamate have been shown in the cerebrospinal fluid, serum, and plasma of patients with MDD and BD 48,49 . Post-mortem studies have reported elevated brain glutamate levels and decreased levels of the glutamatergic NMDA receptor subunits in the frontal cortex of patients with depression 22,50 .…”

Section: Discussionmentioning

confidence: 99%

Mismatch negativity indices and functional outcomes in unipolar and bipolar depression

Kim

Baek

Shim

et al. 2020

Sci Rep

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the aim of the study was to explore the association between functional outcomes and mismatch negativity (MMN) activity in participants with mood disorders. The study participants were 27 subjects with major depressive disorder (MDD), 29 subjects with bipolar disorder (BD), and 33 healthy controls who performed a passive auditory oddball paradigm while electroencephalography (eeG) was recorded. peak amplitudes and source activity of the MMn were compared across groups. Mood and anxiety symptoms were evaluated. the functional levels were the lowest in the BD group, followed by the MDD and healthy control groups. The subjects with BD had significantly lower MMN amplitudes at the frontal and frontocentral electrodes than the healthy controls. the source activity of the MMn from the left anterior cingulate cortex, inferior frontal gyrus, and middle frontal gyrus was significantly increased in the BD group compared to the MDD group. Significant correlations were detected between the functional outcomes and MMn amplitudes at frontal and frontocentral sites. The functional outcome was significantly correlated with left frontal regions. In conclusion, MMN activity appears to be a promising candidate as an evaluation tool for functional outcomes in mood disorders. Bipolar disorder (BD) and major depressive disorder (MDD) are chronic, severe and recurrent mood disorders with substantial disease burden 1. As these two psychiatric conditions both involve severe depressive symptoms, misdiagnosis of BD as unipolar depression is a serious clinical problem 2. Previous studies suggested that C-reactive protein level 3 and heart rate variability 4 are candidate biomarkers for discriminating between bipolar depression and unipolar depression. In addition, electroencephalography (EEG) cordance and coherence values may potentially discriminate unipolar from bipolar depression 5. Although it is important to find biomarkers to enable the differential diagnosis between unipolar and bipolar depression, relatively few studies have addressed this. As such, promising biomarkers to differentiate between the two conditions are needed. Many patients with BD or MDD usually experience serious functional decline 6. Depressive symptoms have been shown to be associated with functional role impairments in multiple domains, such as duties at work or school, responsibilities at home, and relationships with family and friends 7. A previous study found that only 38% patients with major mood disorder achieved functional recovery within 2 years 8. The psychosocial disability resulting from depression is extensive, and encompasses multiple domains, including work and social interactions, independent living in the community, family adjustment, mortality, and quality of life 6. However, it remains unclear why functional decline is so pervasive in mood disorders. In addition, very few studies have assessed the specific biomarkers related to functional decline. Psychosocial functioning is defined as a person's capability to conduct daily life tasks and to engag...

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Section: Discussionmentioning

confidence: 99%

Mismatch negativity indices and functional outcomes in unipolar and bipolar depression

Kim

Baek

Shim

et al. 2020

Sci Rep

View full text Add to dashboard Cite

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“…Despite advances in metabolomics research examining MDD, the majority of these nontargeted or targeted metabolomic studies have had small sample sizes and have reported inconsistent findings, limiting their clinical applicability. To date, a range of meta-analyses has reported decreased levels of tryptophan, kynurenic acid, and kynurenine and increased glutamate levels, in MDD patients [21][22][23]. Despite these studies, which have examined the levels of one or more metabolites, no meta-analyses have been performed examining the metabolomic profiles of MDD.…”

Section: Introductionmentioning

confidence: 99%

An integrated meta-analysis of peripheral blood metabolites and biological functions in major depressive disorder

et al. 2020

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Major depressive disorder (MDD) is a serious mental illness, characterized by high morbidity, which has increased in recent decades. However, the molecular mechanisms underlying MDD remain unclear. Previous studies have identified altered metabolic profiles in peripheral tissues associated with MDD. Using curated metabolic characterization data from a large sample of MDD patients, we meta-analyzed the results of metabolites in peripheral blood. Pathway and network analyses were then performed to elucidate the biological themes within these altered metabolites. We identified 23 differentially expressed metabolites between MDD patients and controls from 46 studies. MDD patients were characterized by higher levels of asymmetric dimethylarginine, tyramine, 2-hydroxybutyric acid, phosphatidylcholine (32:1), and taurochenodesoxycholic acid and lower levels of L-acetylcarnitine, creatinine, L-asparagine, L-glutamine, linoleic acid, pyruvic acid, palmitoleic acid, L-serine, oleic acid, myo-inositol, dodecanoic acid, L-methionine, hypoxanthine, palmitic acid, L-tryptophan, kynurenic acid, taurine, and 25-hydroxyvitamin D compared with controls. L-tryptophan and kynurenic acid were consistently downregulated in MDD patients, regardless of antidepressant exposure. Depression rating scores were negatively associated with decreased levels of L-tryptophan. Pathway and network analyses revealed altered amino acid metabolism and lipid metabolism, especially for the tryptophan-kynurenine pathway and fatty acid metabolism, in the peripheral system of MDD patients. Taken together, our integrated results revealed that metabolic changes in the peripheral blood were associated with MDD, particularly decreased L-tryptophan and kynurenic acid levels, and alterations in the tryptophan-kynurenine and fatty acid metabolism pathways. Our findings may facilitate biomarker development and the elucidation of the molecular mechanisms that underly MDD.

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“…[17][18][19] Conversely, high plasma blood glutamate levels have been reported in those with MDD, and following antidepressant treatment with monoamine-based antidepressants, decreases in blood glutamate levels have been reported. 20,21 It follows that monoamine-based antidepressants impact the glutamatergic system and that the glutamatergic system may be involved in MDD. Regulation of the glutamatergic system to treat mood disorders is typically achieved through interaction with glutamate release or glutamate receptors.…”

Section: Glutamatementioning

confidence: 99%

Keeping up with the clinical advances: depression

2019

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Major depressive disorder (MDD) is a prevalent and heterogeneous disorder. Although there are many treatment options for MDD, patients with treatment-resistant depression (TRD) remain prevalent, wherein delayed time to response results in inferior chances of achieving remission. Recently, therapeutics have been developed that depart from the traditional monoamine hypothesis of depression and focus instead on the glutamatergic, GABAergic, opioidergic, and inflammatory systems. The literature suggests that the foregoing systems are implicated in the pathophysiology of MDD and preclinical trials have informed the development of pharmaceuticals using these systems as therapeutic targets. Pharmaceuticals that target the glutamatergic system include ketamine, esketamine, and rapastinel; brexanolone and SAGE-217 target the GABAergic system; minocycline targets the inflammatory system; and the combinatory agent buprenorphine + samidorphan targets the opioidergic system. The aforementioned agents have shown efficacy in treating MDD in clinical trials. Of particular clinical relevance are those agents targeting the glutamatergic and GABAergic systems as they exhibit rapid response relative to conventional antidepressants. Rapid response pharmaceuticals have the potential to transform the treatment of MDD, demonstrating reduction in depressive symptoms within 24 hours, as opposed to weeks noted with conventional antidepressants. Novel therapeutics have the potential to improve both patient mood symptomatology and economical productivity, reducing the debased human capital costs associated with MDD. Furthermore, a selection of therapeutic targets provides diverse treatment options which may be beneficial to the patient considering the heterogeneity of MDD.

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Elevated peripheral blood glutamate levels in major depressive disorder

Cited by 49 publications

References 37 publications

Mismatch negativity indices and functional outcomes in unipolar and bipolar depression

Mismatch negativity indices and functional outcomes in unipolar and bipolar depression

An integrated meta-analysis of peripheral blood metabolites and biological functions in major depressive disorder

Keeping up with the clinical advances: depression

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