Copyright
©The Author(s) 2021.
World J Psychiatr. Jul 19, 2021; 11(7): 297-315
Published online Jul 19, 2021. doi: 10.5498/wjp.v11.i7.297
Published online Jul 19, 2021. doi: 10.5498/wjp.v11.i7.297
Table 1 Dietary glutamate and depression
Subject | Outcome | Ref. |
Human | In non-obese participants, diets high in levels of glutamic acid were associated with greater depression symptomatology | Kumar et al[43] |
Adult mice | While chronic immobilization stress decreased sodium-coupled neutral amino acid transporter (SNAT)-1 and 2 in neurons and glutamate transporter (GLT)1, SNAT3, and SNAT5 in astrocytes in the medial prefrontal cortex, glutamine—supplemented diet ameliorated these decrements | Baek et al[44] |
Neonatal rats | Subcutaneous injection of monosodium glutamate (MSG) increased the immobility time in the forced swim test and the freezing reaction in the contextual fear conditioning. MSG also increased serotonin uptake in the cerebral cortices and caused deregulation of the hypothalamic-pituitary-adrenal axis | Quines et al[35] |
Mice | Anxiolytic and memory-enhancing effects at low doses of MSG; however, at higher doses, anxiety and memory retardation were observed | Onaolapo et al[45] |
Mice | Higher doses of dietary glutamate resulted in an increase in plasma glutamate and glutamine but no difference in total brain glutamate or glutamine levels | Onaolapo et al[21,45,46] |
Mice | Anxiolytic response in females, and anxiogenic response in males following dietary MSG. A decrease in behavioural despair was observed in both sexes (females more than males) | Onaolapo et al[46,47] |
Mice | Anxiogenic effect was observed following subchronic oral administration of MSG | Onaolapo et al[49] |
Table 2 Endogenous glutamate and depression
Subject | Method | Outcome | Ref. |
Human | Using a proton magnetic resonance spectroscopy technique | Compared to control subjects, glutamine levels in the cerebrospinal fluid of the depressed patients were elevated | Levine et al[54] |
Human | High performance liquid chromatography with fluorometric detection | Plasma levels of glutamate as well as alanine and L-serine were reflective of the severity of depression | Mitani et al[55] |
Human | Single voxel (1)H-Magnetic resonance spectroscopy in 19 patients with major depressive episodes | A significant decrease was observed in the levels of glutamate and glutamine in the anterior cingulate | Auer et al[56] |
Human | Magnetic resonance spectroscopy | Depressed patients had reduced glutamine and glutamate levels in the dorsomedial/dorsal anterolateral prefrontal cortex | Hasler et al[57] |
Human | Magnetic resonance spectroscopy | Compared with controls, depressed patients showed an increase in glutamine levels | Godlewska et al[59] |
Human | Meta-analysis | Decreased levels of glutamatergic metabolites were observed in the medial frontal cortex of depressed subjects | Moriguchi et al[60] |
Human | Meta-analysis | Glutamate and glutamine concentrations were found to be lower in the anterior cingulate cortex in patients compared to controls | Luykx et al[58] |
Human | Functional magnetic resonance imaging and magnetic resonance spectroscopy | Patients with anhedonic major depression showed decreased glutamine but normal glutamate and gamma-aminobutyric acid concentrations | Walter et al[61] |
Human | Resting state functional magnetic resonance imaging | Decreased amplitude of low frequency fluctuation level in right putamen and right middle temporal cortex correlated positively with glutamate concentration in female patients with depression | Zhang et al[66] |
Mice | Preclinical study | Blockade of glutamate transporter-1 in the central amygdala and prefrontal cortex induced both anhedonia and anxiety | John et al[62,63] |
Table 3 Gut brain axis and depression
Subject | Outcome | Ref. |
Germ-free mice | Germ-free (GF) mice showed impaired social interactions, anxiety and derangement of brain-derived neurotrophic factor levels | Crumeyrolle-Arias et al[83], Huo et al[85], and Kamimura et al[86] |
GF and SPF mice | Exposure of GF mice and specific pathogen-free (SPF) mice to chronic restraint stress paradigm revealed an increase in open field exploration time in GF compared to SPF mice. Also, SPF mice exhibited more anxiety-like behavior than GF mice under the same external stress | Arentsen et al[84] |
C57BL/6J male mice | Chronic administration of prebiotic (fructo-oligosaccharides and galacto-oligosaccharides) have been associated with antidepressant and anxiolytic effects | Kamimura et al[86] |
Glutamate and non-glutamate supplemented media | Gamma amino-butyric acid (GABA)-producing Lactococcus lactis strain increased GABA production in the glutamate supplemented medium | Burokas et al[87] |
Table 4 Glutamate-based therapies in depression
Study | Receptor type | Outcome | Ref. |
Randomized, double-blind study | NMDAR antagonist | A single subanaesthetic (0.5 mg/kg) dose of ketamine administered intravenously improved depressive symptoms within 72 h in seven persons with treatment resistant major depressive disorder (MDD) | Berman et al[68] |
Double-blind, placebo-controlled, crossover study | NMDAR antagonist | A single ketamine infusion (0.5 mg/kg over 40 min) had a rapid, robust and mildly sustained antidepressant effect (1 wk) in treatment resistant MDD | Zarate et al[104] |
Open label study | NMDAR antagonist | Rapid anti-depressant effects of a single ketamine infusion in persons with treatment-resistant bipolar depression | DiazGranados et al[105] |
Preclinical | NMDAR antagonist | Memantine exhibited a dose-dependent antidepressant-like response in the tail-suspension test, with the response observed at a dose of 15 mg/kg persisting with sub-chronic administration | Kitanaka et al[112] |
Double-blind placebo controlled | NMDAR antagonist | Memantine administered at doses of between 5-20 mg/d, showed no significant effects on depression phenotypes | Parsons et al[110], Kos and Popik[111], and Muhonen et al[114] |
Preclinical | NMDAR antagonist | The antidepressant effects of amantadine have been observed in situations where it is administered in combination with standard antidepressants such as fluoxetine and imipramine | Czarnecka et al[115] and Maj and Rogóz[116] |
Preclinical | NMDA (NR2B) receptor blockers | Ro 25-6981 exhibited behavioural antidepressant-like effects in the forced swim test | Mathews et al[118] and Refsgaard et al[119] |
Preclinical | NR2B-selective NMDA antagonist | CP-101,606 that was well-tolerated and devoid of psychotropic side effects was also used in a clinical trial involving subjects with traumatic brain injury | Refsgaard et al[119] |
Randomized, placebo-controlled, double-blind study | NR2B-selective NMDA antagonist | CP-101,606 demonstrated efficacy in treatment-refractory MDD subjects | Merchant et al[120] |
Cross-over pilot study | NR2B-selective NMDA antagonist | Oral formulation of MK-0657 in persons with treatment-resistant MDD showed a significant antidepressant effect compared with placebo while no improvement in symptoms was noted using the primary efficacy measure | Preskorn et al[121] |
Preclinical | AMPA-antagonist | LY392098 and LY451616 exhibited antidepressant effects in a number of animal models of depression; including the inescapable stressors, learned-helplessness models, and exposure to chronic mild stress models | Li et al[122] and Lauterborn et al[123] |
Preclinical | mGLu | LY341495, MSG0039, and MPEP exhibited significant antidepressant effects in rodent models of behavioural despair | Jaso et al[7] and Chaki et al[130] |
- Citation: Onaolapo AY, Onaolapo OJ. Glutamate and depression: Reflecting a deepening knowledge of the gut and brain effects of a ubiquitous molecule. World J Psychiatr 2021; 11(7): 297-315
- URL: https://www.wjgnet.com/2220-3206/full/v11/i7/297.htm
- DOI: https://dx.doi.org/10.5498/wjp.v11.i7.297