Glutamate transporters, EAAT1 and EAAT2, are potentially important in the pathophysiology and treatment of schizophrenia and affective disorders

Table 1 The role of EAAT 1 and 2 in psychiatric disorder and medication use

EAAT1	Genetic studies
	BD	SNP rs2731880 T/T genotype associated with worse working memory and selective attention during a depressive episode[102]
		SNP rs2731880 T/T genotype increased negative fMRI BOLD coupling between the amygdala and AnCg[103]
	Scz	SNP rs2731880 T/T genotype associated with worse executive function, verbal fluency and verbal memory[104]
		No association between EAAT1 SNPs rs1428973, rs2033267, rs426040, rs4869684, rs1544795, rs3776585, rs962686, rs2303716, rs3776586, rs1049524, rs1529461 and Scz[112]
	mRNA studies
	MDD	↓Lower levels in the DLPFC[83], AnCg[83], locus coeruleus[105] and hippocampus[106]
		↑Higher cortical levels in suicide completers with a MDD diagnosis compared to those without a diagnosis[118]
	Scz	↑Higher mRNA in the cerebellar vermis[113], AnCg[114], thalamus[115] and prefrontal cortex[116]
		→No change in the DLPFC or primary visual cortex[76,114]
		↓Lower levels in the prefrontal cortex of subjects who completed suicide compared to those who did not[117]
	Medication use	↑Haloperidol has been associated with an increase in EAAT1 mRNA in the thalamic medial dorsal nucleus[121]
		↑Chronic sodium valproate resulted in an upregulation of EAAT1 mRNA in chick cerebellar BGC culture[110]
	Protein studies
	Scz	↓Decreased in the prefrontal cortex[114]
		↓N-glycosylation of EAAT1 monomer was decreased in the AnCg[114,119]
	PTSD	↓Hippocampal EAAT1 protein was lower in a single prolonged stress (SPS) rat model of PTSD[108]
	Medication use	→Clozapine did not affect EAAT1 protein levels in rat[113,122]
		↑Chronic sodium valproate resulted in an upregulation of EAAT1 protein in rat hippocampus and chick cerebellar BGC culture[109,110]
EAAT2	Genetic studies
	Scz	SNP rs4354668 G/G associated with poorer working memory performance[104,138] and a reduction in frontal grey matter[139]
	mRNA studies
	MDD	↓Lower levels in DLPFC and AnCg[83]
		↑Higher levels in subjects who had completed suicide without a diagnosis of MDD compared to those with a diagnosis[118,127]
		↓Lower levels in the hippocampus, cerebral cortex and striatum of a rat model of depression[128,129]
	Scz	↓Lower levels in the parahippocampal gyrus[140] and prefrontal cortex[141]
		↑Higher levels in the thalamus[115] and prefrontal cortex[142]
		→No change in EAAT2 or EAAT2b mRNA in the DLPFC or primary visual cortex[76]
	Medication use	↓Clozapine decreased levels in hippocampal CA1, parietal temporal, frontal and cingulate cortical[144], and striatal[145] brain regions of male Sprague-Dawley rats
		↓Haloperidol decreased frontal and cingulate cortical[144], as well as striatal[145], EAAT2 expression in rat
		↓Levels were higher in untreated subjects with Scz than in those prescribed typical or atypical antipsychotics[142]
		↓Increased levels caused by chronic stress were normalised by tianeptine treatment in rat[130]
		↓Increased hippocampal levels caused by stress were normalised by lithium administration in rat[137]
		↑Fluoxetine increased rat hippocampal and cortical levels[136]
		↑Tranylcypromine increased levels in rat amygdala[136]
	Protein studies
	Scz	↓ N-glycosylation of EAAT2 multimer was lower in the DLPFC[119]
		↑ EAAT2b increased in extrasynaptic membrane/cytosol fractions from the DLPFC[143]
	PTSD	↓Hippocampal EAAT2 protein was lower in the single prolonged stress (SPS) rat model of PTSD[108]
	Medication use	↓Clozapine decreased protein levels in astrocyte culture[147]
		↓Clozapine reduced protein levels in the cerebral cortex of adult rats[146]
		↓Increased levels caused by chronic stress were normalised by tianeptine treatment in rat[130]
		→Increases in EAAT2b protein caused by chronic stress were unaffected by tianeptine treatment in rat[130]
		↑Chronic sodium valproate increased hippocampal EAAT2 protein in rat[109]

All research refers to human studies unless explicitly stated otherwise. References numbered as they are in the Reference section. ↑: Increase; ↓: Decrease; →: No change; AnCg: Anterior cingulate cortex; BGC: Bergmann glia cell; DLPFC: Dorsolateral prefrontal cortex; BD: Bipolar disorders; BOLD: Blood-oxygen dependent contrast imaging; fMRI: Functional magnetic resonance imaging; MDD: Major depressive disorders; PTSD: Post-traumatic stress disorder; Scz: Schizophrenia.