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]